Evaluating the Effect of Ramadan Fasting on Muslim Patients with Diabetes in relation to Use of Medication and Lifestyle Patterns: A Prospective Study

PubMed Central

Siaw, Melanie Yee Lee; Chew, Daniel Ek Kwang; Dalan, Rinkoo; Abdul Shakoor, Shaikh Abdul Kader Kamaldeen; Othman, Noorani; Choo, Chor Hui; Shamsuri, Nur Hidayah; Abdul Karim, Siti Nurhana; Chan, Sui Yung; Lee, Joyce Yu-Chia

2014-01-01

Objectives. This study aimed to examine the effect of Ramadan fasting on HbA1c in Muslim patients with type 2 diabetes. The incidence of hypoglycemia and glycemic changes in relation to the adjustment of doses of antidiabetic agents, diet, and physical activity during Ramadan was also evaluated. Methods. This was a prospective study conducted in an outpatient endocrine clinic. A set of questionnaires was administered to Muslim patients with diabetes who fasted for ≥10 days. Those who were hospitalized for diabetic ketoacidosis or severe hypoglycemia a month prior to Ramadan or were given short-term corticosteroid therapy were excluded. The patients' responses and clinical outcomes from the clinic database were collected before, during, and after Ramadan. Results. A total of 153 participants completed the study. The mean HbA1c improved from 8.9% before Ramadan to 8.6% during Ramadan (P < 0.05). Although diet and physical activity did not contribute to changes in glycemia, a significant improvement in HbA1c was observed in patients who had adjustments made to their doses of antidiabetic agents during Ramadan (P < 0.001). In addition, their rate of hypoglycemia was minimal. Conclusions. Ramadan fasting appeared to improve glycemic control, especially in those whose doses of antidiabetic agents were adjusted during Ramadan. PMID:25435876

Anti-Diabetic Effects of Dung Beetle Glycosaminoglycan on db Mice and Gene Expression Profiling.

PubMed

Ahn, Mi Young; Kim, Ban Ji; Yoon, Hyung Joo; Hwang, Jae Sam; Park, Kun-Koo

2018-04-01

Anti-diabetes activity of Catharsius molossus (Ca, a type of dung beetle) glycosaminoglycan (G) was evaluated to reduce glucose, creatinine kinase, triglyceride and free fatty acid levels in db mice. Diabetic mice in six groups were administrated intraperitoneally: Db heterozygous (Normal), Db homozygous (CON), Heuchys sanguinea glycosaminoglycan (HEG, 5 mg/kg), dung beetle glycosaminoglycan (CaG, 5 mg/kg), bumblebee ( Bombus ignitus ) queen glycosaminoglycan (IQG, 5 mg/kg) and metformin (10 mg/kg), for 1 month. Biochemical analyses in the serum were evaluated to determine their anti-diabetic and anti-inflammatory actions in db mice after 1 month treatment with HEG, CaG or IQG treatments. Blood glucose level was decreased by treatment with CaG. CaG produced significant anti-diabetic actions by inhiting creatinine kinase and alkaline phosphatase levels. As diabetic parameters, serum glucose level, total cholesterol and triglyceride were significantly decreased in CaG5-treated group compared to the controls. Dung beetle glycosaminoglycan, compared to the control, could be a potential therapeutic agent with anti-diabetic activity in diabetic mice. CaG5-treated group, compared to the control, showed the up-regulation of 48 genes including mitochondrial yen coded tRNA lysine (mt-TK), cytochrome P450, family 8/2, subfamily b, polypeptide 1 (Cyp8b1), and down-regulation of 79 genes including S100 calcium binding protein A9 (S100a9) and immunoglobulin kappa chain complex (Igk), and 3-hydroxy-3-methylglutaryl-CoenzymeAsynthase1 (Hmgcs1). Moreover, mitochondrial thymidine kinase (mt-TK), was up-regulated, and calgranulin A (S100a9) were down-regulated by CaG5 treatment, indicating a potential therapeutic use for anti-diabetic agent.

A review of the efficacy and safety of oral antidiabetic drugs

PubMed Central

Stein, Stephanie Aleskow; Lamos, Elizabeth Mary; Davis, Stephen N

2014-01-01

Introduction Additional oral antidiabetic agents to metformin, sulfonylureas (SU) and thiazolidinediones (TZD) are approved for the treatment of type 2 diabetes. Areas covered The efficacy and safety of metformin, SUs, TZDs, dipeptidyl peptidase-IV (DPP-4) inhibitors, meglitinide analogs, α-glucosidase inhibitors (AGIs), bile-acid sequestrants (BAS) and bromocriptine will be reviewed. Expert opinion Several new oral agents have been approved for type 2 diabetes management in recent years. It is important to understand the efficacy and safety of these medications in addition to the older agents to best maximize oral drug therapy for diabetes. Of the recently introduced oral hypoglycemic/antihyperglycemic agents, the DPP-4 inhibitors are moderately efficacious compared with mainstay treatment with metformin with a low side-effect profile and have good efficacy in combination with other oral agents and insulin. They are a recommended alternative when metformin use is limited by gastrointestinal (GI) side effects or when SU treatment results in significant hypoglycemia or weight gain. Meglitinide analogs are limited by their frequent dosing, expense and hypoglycemia (repaglinide > nateglinide), while AGIs are also limited by their dosing schedule and GI side-effect profile. BAS and bromocriptine have the lowest efficacy with regard to HbA1c reduction, also are plagued by GI adverse reactions, but have a low risk of hypoglycemia. PMID:23241069

A systematic and critical review on bioanalytical method validation using the example of simultaneous quantitation of antidiabetic agents in blood.

PubMed

Fachi, Mariana Millan; Leonart, Letícia Paula; Cerqueira, Letícia Bonancio; Pontes, Flavia Lada Degaut; de Campos, Michel Leandro; Pontarolo, Roberto

2017-06-15

A systematic and critical review was conducted on bioanalytical methods validated to quantify combinations of antidiabetic agents in human blood. The aim of this article was to verify how the validation process of bioanalytical methods is performed and the quality of the published records. The validation assays were evaluated according to international guidelines. The main problems in the validation process are pointed out and discussed to help researchers to choose methods that are truly reliable and can be successfully applied for their intended use. The combination of oral antidiabetic agents was chosen as these are some of the most studied drugs and several methods are present in the literature. Moreover, this article may be applied to the validation process of all bioanalytical. Copyright © 2017 Elsevier B.V. All rights reserved.

Enzymes inhibition and antidiabetic effect of isolated constituents from Dillenia indica.

PubMed

Kumar, Sunil; Kumar, Vipin; Prakash, Om

2013-01-01

This study was designed to investigate the enzyme inhibitory and antidiabetic activity for the constituents isolated from Dillenia indica. The leaves of D. indica were extracted with methanol and subjected to fractionation and chromatographic separation, which led to the isolation of seven compounds: betulinic acid (1), n-heptacosan-7-one (2), n-nonatriacontan-18-one (3), quercetin (4), β sitosterol (5), stigmasterol (6), and stigmasteryl palmitate (7). Among these isolates, compounds 1, 4, 5, and 6 were evaluated for in vitro enzyme inhibition and compounds 4, 5 and 6 were evaluated for antidiabetic activity in streptozotocin-nicotinamide induced diabetic mice. Compounds 1, 4, 5, and 6 showed 47.4, 55.2, 48.8, and 44.3% α -amylase inhibition, respectively, and 52.2, 78.2, 52.5, and 34.2% α -glucosidase inhibition, respectively, at the dose of 50 µg/kg. Compounds 4, 5 and 6 also showed significant (∗P < 0.05) antidiabetic activity in streptozotocin-nicotinamide induced diabetic mice at the dose of 10 mg/kg. These results provide evidence that Dillenia indica might be a potential source of antidiabetic agents.

Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

PubMed Central

Betônico, Carolina C R; Titan, Silvia M O; Correa-Giannella, Maria Lúcia C; Nery, Márcia; Queiroz, Márcia

2016-01-01

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population. PMID:26872083

Garlic as an anti-diabetic agent: recent progress and patent reviews.

PubMed

Padiya, Raju; Banerjee, Sanjay K

2013-08-01

This article reviews recent literature on the usage and relevance of garlic and its bioactive components in controlling diabetes and diabetes-associated pathologies; and also updates recent patents on the subject. Antidiabetic effect of garlic is well documented even in ancient medical literature. Garlic and its active ingredients have been extensively studied for their antidiabetic efficacies in either experimentally induced or genetic animal models of diabetes. Human studies are also available where hypoglycemic effect of garlic was reported. The beneficial effects of garlic are mainly attributed to the presence of volatile sulfur compounds like alliin, allicin, diallyl disulfide, diallyl trisulfide, diallyl sulfide, S-allyl cysteine, ajoene and allyl mercaptan. Garlic and garlic extracts have been shown to be effective in reducing insulin resistance. Therefore, considering the importance of garlic in controlling diabetic complications, several preparations and food processes containing garlic have been patented. This review discusses some of the recent progresses made in this field and consolidates the results.

Effectiveness and tolerability of second-line therapy with vildagliptin versus other oral agents in type 2 diabetes (EDGE): post-hoc subanalysis of the Belgian data.

PubMed

Hoste, J; Daci, E; Mathieu, C

2014-06-01

To assess the efficacy and safety of vildagliptin versus other oral glucose-lowering drugs added to antidiabetic monotherapy in Belgian patients with type 2 diabetes mellitus, in comparison to the global EDGE study results. This is a pre-specified post-hoc subanalysis of the Belgian patient cohort from a worldwide 1-year observational study that compared the effectiveness and tolerability of vildagliptin to other oral antidiabetic agents in type 2 diabetes patients failing monotherapy with oral glucose-lowering agents (EDGE). A total of 1793 Belgian patients were enrolled. Physicians could add any oral antidiabetic drug and patients entered either into the vildagliptin or the comparator cohort. The primary effectiveness and tolerability endpoint was defined as the proportion of patients having a treatment response (HbA1c reduction from baseline to month 12 endpoint >0·3%) without hypoglycemia, weight gain, peripheral oedema, or gastrointestinal side-effects. In the Belgian population, 37·8% of patients in the vildagliptin group and 32·8% in the comparator group had a decrease in HbA1c of >0·3% without the predefined tolerability issues of hypoglycemia, weight gain, oedema or, gastrointestinal complaints (primary endpoint), resulting in an unadjusted odds ratio of 1·24 (95% CI: 0·96-1·61). Mean HbA1c change from baseline was -0·81% in the vildagliptin cohort and -0·75% in the comparator cohort. Overall, vildagliptin was well tolerated with similarly low incidences of total adverse events (14·9% versus 14·5% in the compactor group) and serious adverse events (2·7% versus 2·5% in the comparator group). In this EDGE subgroup of Belgian patients with type 2 diabetes who do not achieve the glycemic targets with monotherapy, a similar trend as in the global EDGE study was observed. Adding vildagliptin as a second oral glucose-lowering agent resulted in lowering HbA1c to <7% without weight gain, hypoglycemia or peripheral oedema in a higher proportion of patients than comparator oral antidiabetic drugs, with no differences in the reported number of adverse events.

Comparative Study of Antidiabetic Activity and Oxidative Stress Induced by Zinc Oxide Nanoparticles and Zinc Sulfate in Diabetic Rats.

PubMed

Nazarizadeh, Ali; Asri-Rezaie, Siamak

2016-08-01

In the current study, antidiabetic activity and toxic effects of zinc oxide nanoparticles (ZnO) were investigated in diabetic rats compared to zinc sulfate (ZnSO4) with particular emphasis on oxidative stress parameters. One hundred and twenty male Wistar rats were divided into two healthy and diabetic groups, randomly. Each major group was further subdivided into five subgroups and then orally supplemented with various doses of ZnO (1, 3, and 10 mg/kg) and ZnSO4 (30 mg/kg) for 56 consecutive days. ZnO showed greater antidiabetic activity compared to ZnSO4 evidenced by improved glucose disposal, insulin levels, and zinc status. The altered activities of erythrocyte antioxidant enzymes as well as raised levels of lipid peroxidation and a marked reduction of total antioxidant capacity were observed in rats receiving ZnO. ZnO nanoparticles acted as a potent antidiabetic agent, however, severely elicited oxidative stress particularly at higher doses.

A REVIEW ON SOME ANTIDIABETIC PLANTS OF INDIA

PubMed Central

Rai, M.K.

1995-01-01

The control over diabetes mellitus depends upon the availability of insulin. Various efforts have been made in the recent past to control / check it. There is an increasing demand to use the natural antidiabetic agents. The literature pertaining to antidiabetic herbs is scattered. The present article is a conglomeration of available indigenous literature. It gives an additional information of list of antidiabetic plants which have not been discussed by Nagarajan et al76 and Handa et al45. It also presents some common plants used in diabetes, and the future of hypoglycaemic herbal drugs. PMID:22556695

Impact of insulin treatment in diabetic macular edema therapy in type 2 diabetes.

PubMed

Matsuda, Simone; Tam, Tiffany; Singh, Rishi P; Kaiser, Peter K; Petkovsek, Daniel; Zanella, Maria Teresa; Ehlers, Justis P

2015-02-01

To evaluate the impact of insulin therapy on the outcomes of diabetic macular edema (DME) treatment with vascular endothelial growth factor (VEGF) inhibitors in people with type 2 diabetes. A retrospective consecutive case series of 95 patients with type 2 diabetes and DME who were treated with anti-VEGF therapy. We examined 2 cohorts: patients taking only oral antidiabetic agents and patients on insulin therapy. The main outcome measures were change in visual acuity and change in central subfield macular thickness measured by spectral-domain optical coherence tomography. The additional variables analyzed included glycated hemoglobin (A1C), creatinine, blood pressure and body mass index and their correlations with clinical findings. Both groups had a statistically significant improvement in visual acuity (oral antidiabetic agents group: 20/61 to 20/49, p=0.003; insulin therapy group: 20/76 to 20/56, p=0.005). There was no difference between groups at initial or 12-month examination (p=0.239 and p=0.489, respectively). From an anatomic standpoint, central subfield macular thickness also improved significantly in both groups: from 454.7 μm to 354.9 μm (p<0.001) in the oral antidiabetic agents group and from 471.5 μm to 368.4 μm (p<0.001) in the insulin therapy group. Again, there was no significant difference between groups at initial or 12-month follow-up examinations (p=0.586 and p=0.591, respectively). Mean A1C levels remained relatively stable during the follow up in both groups. Anti-VEGF therapy is a useful treatment for DME. This study suggests that chronic insulin therapy, compared with oral antidiabetic agents, does not modify the anatomic or functional effectiveness of DME treatment. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Insulin sparing action of adenovirus 36 and its E4orf1 protein.

PubMed

Dhurandhar, Nikhil V

2013-01-01

Additional drugs are required to effectively manage diabetes and its complications. Recent studies have revealed protective effects of Ad36, a human adenovirus, and its E4orf1 protein on glucose disposal, which may be creatively harnessed to develop novel anti-diabetic agents. Experimental Ad36 infection improves hyperglycemia in animal models and natural Ad36 infection in humans is associated with better glycemic control. Available data indicate distinctive advantages for a drug that may mimic the action of Ad36/E4orf1. The key features of such a potential drug include the ability to increase glucose uptake by adipose tissue and skeletal muscle, to reduce hepatic glucose output independent of proximal insulin signaling, and to up-regulate adiponectin and its hepatic action. The effect of Ad36/E4orf1 on hepatocyte metabolism suggests a role for treating hepatic steatosis. Despite these potential advantages, considerable research is required before such a drug is developed. The in vivo efficacy and safety of E4orf1 in improving hyperglycemia remain unknown, and an appropriate drug delivery system is required. Nonetheless, Ad36 E4orf1 offers a research opportunity to develop a new anti-diabetic agent with multiple potential advantages and conceptually advances the use of a rather unconventional source, microbial proteins, for anti-diabetic drug development. Copyright © 2013 Elsevier Inc. All rights reserved.

Enzymes Inhibition and Antidiabetic Effect of Isolated Constituents from Dillenia indica

PubMed Central

Kumar, Sunil; Kumar, Vipin; Prakash, Om

2013-01-01

Aims. This study was designed to investigate the enzyme inhibitory and antidiabetic activity for the constituents isolated from Dillenia indica. Methods. The leaves of D. indica were extracted with methanol and subjected to fractionation and chromatographic separation, which led to the isolation of seven compounds: betulinic acid (1), n-heptacosan-7-one (2), n-nonatriacontan-18-one (3), quercetin (4), β sitosterol (5), stigmasterol (6), and stigmasteryl palmitate (7). Among these isolates, compounds 1, 4, 5, and 6 were evaluated for in vitro enzyme inhibition and compounds 4, 5 and 6 were evaluated for antidiabetic activity in streptozotocin-nicotinamide induced diabetic mice. Results. Compounds 1, 4, 5, and 6 showed 47.4, 55.2, 48.8, and 44.3% α-amylase inhibition, respectively, and 52.2, 78.2, 52.5, and 34.2% α-glucosidase inhibition, respectively, at the dose of 50 µg/kg. Compounds 4, 5 and 6 also showed significant (∗P < 0.05) antidiabetic activity in streptozotocin-nicotinamide induced diabetic mice at the dose of 10 mg/kg. Conclusion. These results provide evidence that Dillenia indica might be a potential source of antidiabetic agents. PMID:24307994

Non-coding RNAs and Berberine: A new mechanism of its anti-diabetic activities.

PubMed

Chang, Wenguang

2017-01-15

Type 2 Diabetes (T2D) is a metabolic disease with high mortality and morbidity. Non-coding RNAs, including small and long non-coding RNAs, are a novel class of functional RNA molecules that regulate multiple biological functions through diverse mechanisms. Studies in the last decade have demonstrated that non-coding RNAs may represent compelling therapeutic targets and play important roles in regulating the course of insulin resistance and T2D. Berberine, a plant-based alkaloid, has shown promise as an anti-hyperglycaemic, anti-hyperlipidaemic agent against T2D. Previous studies have primarily focused on a diverse array of efficacy end points of berberine in the pathogenesis of metabolic syndromes and inflammation or oxidative stress. Currently, an increasing number of studies have revealed the importance of non-coding RNAs as regulators of the anti-diabetic effects of berberine. The regulation of non-coding RNAs has been associated with several therapeutic actions of berberine in T2D progression. Thus, this review summarizes the anti-diabetic mechanisms of berberine by focusing on its role in regulating non-coding RNA, thus demonstrating that berberine exerts global anti-diabetic effects by targeting non-coding RNAs and that these effects involve several miRNAs, lncRNAs and multiple signal pathways, which may enhance the current understanding of the anti-diabetic mechanism actions of berberine and provide new pathological targets for the development of berberine-related drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

[New SGLT2 inhibitor empagliflozin: modern and safe treatment of diabetes].

PubMed

Rušavý, Zdeněk

2014-11-01

Empagliflozin is agent of new antidiabetic drugs that cause glycosuria blocking the glucose reuptake in the proxi-mal tubule. The loss of 50-100 g of glucose / 24 hours in the urine results in a reduction of fasting glucose, especially post-prandial glucose, the energy expenditure of 200-400 kcal / day and blood pressure lowering. Treatment efficacy does not decrease over time, as it is not dependent on its own insulin production. The work evaluates the safety of modern treatment with empagliflozin which will soon appear in the portfolio of antidiabetic agents in the Czech Republic. The conducted studies with a special focus on empagliflozin treatment have shown high efficacy, safety and good tolerability of drug. It has been described a higher incidence of genital infections with non-severe course, especially in women. The drug does not cause hypoglycaemia. In combination with sulfonylurea hypoglycaemia may occur. Empagliflozin does not cause clinically significant dehydration or hypotension in patients about 60 years of age, but some caution in empagliflozin treatment should be in elderly and fragile patients. The big convenience of empagliflozin is its clinically non-significant interactions with other drugs and simple dosage of 1 tablet / day orally. In conclusion, empagliflozin is highly effective oral antidiabetic agent with a potential of wide application in all stages of type 2 diabetes in monotherapy or combined with other medication. The treatment is associated with weight loss and blood pressure lowering. The drug is effective and safe until eGFR 45 ml / s, in lower values the treatment should be discontinued. The occurrence of side effects is rare, except increased incidence of genital infections especially in women and increased risk of hypoglycaemia when empagliflozin is combined with sulfonylurea.

A pharmacological appraisal of medicinal plants with antidiabetic potential

PubMed Central

Khan, Vasim; Najmi, Abul Kalam; Akhtar, Mohd.; Aqil, Mohd.; Mujeeb, Mohd.; Pillai, K. K.

2012-01-01

Diabetes mellitus is a complicated metabolic disorder that has gravely troubled the human health and quality of life. Conventional agents are being used to control diabetes along with lifestyle management. However, they are not entirely effective and no one has ever been reported to have fully recovered from diabetes. Numerous medicinal plants have been used for the management of diabetes mellitus in various traditional systems of medicine worldwide as they are a great source of biological constituents and many of them are known to be effective against diabetes. Medicinal plants with antihyperglycemic activities are being more desired, owing to lesser side-effects and low cost. This review focuses on the various plants that have been reported to be effective in diabetes. A record of various medicinal plants with their established antidiabetic and other health benefits has been reported. These include Allium sativa, Eugenia jambolana, Panax ginseng, Gymnema sylvestre, Momrodica charantia, Ocimum sanctum, Phyllanthus amarus, Pterocarpus marsupium, Trigonella foenum graecum and Tinospora cordifolia. All of them have shown a certain degree of antidiabetic activity by different mechanisms of action. PMID:22368396

Trivaric acid, a new inhibitor of PTP1b with potent beneficial effect on diabetes.

PubMed

Sun, Wenlong; Zhang, Bowei; Zheng, Haizhou; Zhuang, Chunlin; Li, Xia; Lu, Xinhua; Quan, Chunshan; Dong, Yuesheng; Zheng, Zhihui; Xiu, Zhilong

2017-01-15

To screen a potential PTP1b inhibitor from the microbial origin-based compound library and to investigate the potential anti-diabetic effects of the inhibitor in vivo and determine its primary anti-diabetic mechanism in vitro and in silico. PTP1b inhibitory activity was measured using recombination protein as the enzyme and p-NPP as the substrate. The binding of the inhibitor to PTP1b was analysed by docking in silico and confirmed by ITC experiments. The intracellular signalling pathway was detected by Western blot analysis in HepG2 cells. The anti-diabetic effects were evaluated using a diabetic mice model in vivo. Among 545 microbial origin-based pure compounds tested, trivaric acid, a tridepside, was selected as a PTP1B inhibitor exhibiting strong inhibitory activity with an IC 50 of 173nM. Docking and ITC studies showed that trivaric acid was able to spontaneously bind to PTP1b and may inhibit PTP1b by blocking the catalytic domain of the phosphatase. Trivaric acid also enhanced the ability of insulin to stimulate the IR/IRS/Akt/GLUT2 pathway and increase the glucose consumption in HepG2 cells. In diabetic mice, trivaric acid that had been encapsulated into Eudrgit L100-5.5 showed significant anti-diabetic effects, improving insulin resistance, leptin resistance and lipid profile and weight control at doses of 5mg/kg and 50mg/kg. Trivaric acid is a potential lead compound in the search for anti-diabetic agents targeting PTP1b. Copyright © 2016 Elsevier Inc. All rights reserved.

Honey and Diabetes: The Importance of Natural Simple Sugars in Diet for Preventing and Treating Different Type of Diabetes

PubMed Central

Dezmirean, Daniel S.

2018-01-01

Diabetes is a metabolic disorder with multifactorial and heterogeneous etiologies. Two types of diabetes are common among humans: type 1 diabetes that occurs when the immune system attacks and destroys insulin and type 2 diabetes, the most common form, that may be caused by several factors, the most important being lifestyle, but also may be determined by different genes. Honey was used in folk medicine for a long time, but the health benefits were explained in the last decades, when the scientific world was concerned in testing and thus explaining the benefits of honey. Different studies demonstrate the hypoglycemic effect of honey, but the mechanism of this effect remains unclear. This review presents the experimental studies completed in the recent years, which support honey as a novel antidiabetic agent that might be of potential significance for the management of diabetes and its complications and also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. PMID:29507651

Vildagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus

PubMed Central

Profit, Louise; Chrisp, Paul; Nadin, Carole

2008-01-01

Introduction: Type 2 diabetes is increasing in prevalence worldwide and is a leading cause of morbidity and mortality, mainly due to the development of complications. Vildagliptin is an inhibitor of dipeptidyl peptidase 4 (DPP-4), a new class of oral antidiabetic agents. Aims: To evaluate the role of vildagliptin in the management of type 2 diabetes. Evidence review: Clear evidence shows that vildagliptin improves glycemic control (measured by glycosylated hemoglobin and blood glucose levels) more than placebo in adults with type 2 diabetes, either as monotherapy or in combination with metformin. Vildagliptin is as effective as pioglitazone and rosiglitazone, and slightly less effective than metformin, although better tolerated. Further glycemic control is achieved when adding vildagliptin to metformin, pioglitazone, or glimepride. There is evidence that vildagliptin improves beta-cell function and insulin sensitivity. Vildagliptin does not appear to be associated with weight gain or with a higher risk of hypoglycemia than placebo or other commonly used oral antidiabetic agents. Economic evidence is currently lacking. Place in therapy: Vildagliptin improves glycemic control with little if any weight gain or hypoglycemia in adult patients with type 2 diabetes when given alone or in combination with metformin, thiazolidinediones, or sulfonylureas. Since many diabetic patients require combination therapy, the complementary mechanism of action of vildagliptin and other commonly prescribed antidiabetic drugs represents an important new therapeutic option in diabetes management. PMID:20694081

The Impact of Weight Gain on Motivation, Compliance, and Metabolic Control in Patients with Type 2 Diabetes Mellitus

PubMed Central

Pi-Sunyer, F. Xavier

2010-01-01

Patients with type 2 diabetes, approximately 85% of whom are overweight or obese, often have an increased incidence of cardiovascular disease (CVD) risk factors such as hypertension and dyslipidemia. Both type 2 diabetes and obesity are independent risk factors for CVD. Unfortunately, many therapies aimed at maintaining and improving glucose control are associated with weight gain. Among the older antidiabetes agents, most, including the insulin secretagogues and sensitizers, can lead to weight gain, except for metformin, which is weight-neutral. Among the newer agents, the dipeptidyl peptidase-4 inhibitors generally are weight-neutral in addition to lowering glucose, while the glucagon-like peptide–1 receptor agonists lead to weight reduction. Patients with type 2 diabetes are at an increased risk for both diabetes-and CV-related outcomes, and weight reduction is an important component of diabetes management. Weight gain in patients with type 2 diabetes can contribute to patient frustration and may negatively impact their compliance to therapeutic regimens. The selection of antidiabetes agents that not only improve glucose control but reduce or have a neutral effect on weight with beneficial effects on lipids are ideal options for managing patients with type 2 diabetes. PMID:19820278

Fishing for Nature's Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products.

PubMed

Tabassum, Nadia; Tai, Hongmei; Jung, Da-Woon; Williams, Darren R

2015-01-01

Diabetes mellitus affects millions of people worldwide and significantly impacts their quality of life. Moreover, life threatening diseases, such as myocardial infarction, blindness, and renal disorders, increase the morbidity rate associated with diabetes. Various natural products from medicinal plants have shown potential as antidiabetes agents in cell-based screening systems. However, many of these potential "hits" fail in mammalian tests, due to issues such as poor pharmacokinetics and/or toxic side effects. To address this problem, the zebrafish (Danio rerio) model has been developed as a "bridge" to provide an experimentally convenient animal-based screening system to identify drug candidates that are active in vivo. In this review, we discuss the application of zebrafish to drug screening technologies for diabetes research. Specifically, the discovery of natural product-based antidiabetes compounds using zebrafish will be described. For example, it has recently been demonstrated that antidiabetic natural compounds can be identified in zebrafish using activity guided fractionation of crude plant extracts. Moreover, the development of fluorescent-tagged glucose bioprobes has allowed the screening of natural product-based modulators of glucose homeostasis in zebrafish. We hope that the discussion of these advances will illustrate the value and simplicity of establishing zebrafish-based assays for antidiabetic compounds in natural products-based laboratories.

Protein tyrosine phosphatase 1B (PTP1B) inhibitors from Morinda citrifolia (Noni) and their insulin mimetic activity.

PubMed

Nguyen, Phi-Hung; Yang, Jun-Li; Uddin, Mohammad N; Park, So-Lim; Lim, Seong-Il; Jung, Da-Woon; Williams, Darren R; Oh, Won-Keun

2013-11-22

As part of our ongoing search for new antidiabetic agents from medicinal plants, we found that a methanol extract of Morinda citrifolia showed potential stimulatory effects on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation of this active extract yielded two new lignans (1 and 2) and three new neolignans (9, 10, and 14), as well as 10 known compounds (3-8, 11-13, and 15). The absolute configurations of compounds 9, 10, and 14 were determined by ECD spectra analysis. Compounds 3, 6, 7, and 15 showed inhibitory effects on PTP1B enzyme with IC50 values of 21.86 ± 0.48, 15.01 ± 0.20, 16.82 ± 0.42, and 4.12 ± 0.09 μM, respectively. Furthermore, compounds 3, 6, 7, and 15 showed strong stimulatory effects on 2-NBDG uptake in 3T3-L1 adipocyte cells. This study indicated the potential of compounds 3, 6, 7, and 15 as lead molecules for antidiabetic agents.

Studies on the Antidiabetic Activities of Cordyceps militaris Extract in Diet-Streptozotocin-Induced Diabetic Sprague-Dawley Rats

PubMed Central

Dong, Yuan; Jing, Tianjiao; Meng, Qingfan; Liu, Chungang; Hu, Shuang; Ma, Yihang; Liu, Yan; Lu, Jiahui; Cheng, Yingkun; Teng, Lirong

2014-01-01

Due to substantial morbidity and high complications, diabetes mellitus is considered as the third “killer” in the world. A search for alternative antidiabetic drugs from herbs or fungi is highly demanded. Our present study aims to investigate the antidiabetic activities of Cordyceps militaris on diet-streptozotocin-induced type 2 diabetes mellitus in rats. Diabetic rats were orally administered with water extract or alcohol extract at 0.05 g/kg and 2 g/kg for 3 weeks, and then, the factors levels related to blood glucose, lipid, free radicals, and even nephropathy were determined. Pathological alterations on liver and kidney were examined. Data showed that, similar to metformin, Cordyceps militaris extracts displayed a significant reduction in blood glucose levels by promoting glucose metabolism and strongly suppressed total cholesterol and triglycerides concentration in serum. Cordyceps militaris extracts exhibit antioxidative effects indicated by normalized superoxide dismutase and glutathione peroxidase levels. The inhibitory effects on blood urea nitrogen, creatinine, uric acid, and protein revealed the protection of Cordyceps militaris extracts against diabetic nephropathy, which was confirmed by pathological morphology reversion. Collectively, Cordyceps militaris extract, a safe pharmaceutical agent, presents excellent antidiabetic and antinephropathic activities and thus has great potential as a new source for diabetes treatment. PMID:24738047

Evidence based study of antidiabetic potential of C. maxima seeds - In vivo.

PubMed

Kushawaha, Devesh Kumar; Yadav, Manjulika; Chatterji, Sanjukta; Srivastava, Amrita Kumari; Watal, Geeta

2017-10-01

In vitro antidiabetic efficacy of Cucurbita maxima seed extract (CMSE) has already been studied in our previous findings. Thus, in order to validate these findings in biological system, in vivo antidiabetic activity of aqueous extract was investigated in normal as well as diabetic experimental models. Variable doses of extract were administered orally to normal and STZ induced mild diabetic rats during fasting blood glucose (FBG) and glucose tolerance test (GTT) studies. In order to determine the extract's antidiabetic potential long-term FBG and post prandial glucose (PPG) studies were also carried out. Most effective dose of 200 mg kg -1 of CMSE decreases the blood glucose level (BGL) in normal rats by 29.02% at 6 h during FBG studies and 23.23% at 3 h during GTT. However, the maximum reduction observed in BGL of mild diabetic rats during GTT the same interval of time was 26.15%. Moreover, in case of severely diabetic rats a significant reduction of 39.33% was observed in FBG levels whereas, in case of positive control, rats treated with 2.5 mg kg -1 of glipizide, a fall of 42.9% in FBG levels was observed after 28 days. Results of PPG level also showed a fall of 33.20% in severely diabetic rats as compared to the positive control showing a fall of 44.2% at the end of the 28 days. Thus, the present study validate the hypoglycemic and antidiabetic effect of CMSE and hence this extract could be explored further for developing as a novel antidiabetic agent.

Lack of pharmacokinetic interaction for ISIS 113715, a 2'-0-methoxyethyl modified antisense oligonucleotide targeting protein tyrosine phosphatase 1B messenger RNA, with oral antidiabetic compounds metformin, glipizide or rosiglitazone.

PubMed

Geary, Richard S; Bradley, JoAnn D; Watanabe, Tanya; Kwon, Younggil; Wedel, Mark; van Lier, Jan J; VanVliet, André A

2006-01-01

ISIS 113715 is a 20-mer phosphorothioate antisense oligonucleotide (ASO) that is complementary to the protein tyrosine phosphatase 1B (PTP-1B) messenger RNA and subsequently reduces translation of the PTP-1B protein, a negative regulator of insulin receptor. ISIS 113715 is currently being studied in early phase II clinical studies to determine its ability to improve or restore insulin receptor sensitivity in patients with type 2 diabetes mellitus. Future work will investigate the combination of ISIS 113715 with antidiabetic compounds. In vitro ultrafiltration human plasma protein binding displacement studies and a phase I clinical study were used to characterise the potential for pharmacokinetic interaction of ISIS 113715 and three marketed oral antidiabetic agents. ISIS 113715 was co-incubated with glipizide and rosiglitazone in whole human plasma and tested for increased free drug concentrations. In a phase I clinical study, 23 healthy volunteers received a single oral dose of an antidiabetic compound (either metformin, glipizide or rosiglitazone) both alone and together with subcutaneous ISIS 113715 200 mg in a sequential crossover design. A comparative pharmacokinetic analysis was performed to determine if there were any effects that resulted from coadministration of ISIS 113715 with these antidiabetic compounds. In vitro human plasma protein binding displacement studies showed only minor effects on rosiglitazone and no effect on glipizide when co-incubated with ISIS 113715. The results of the phase I clinical study further indicate that there were no measurable changes in glipizide (5 mg), metformin (500 mg) or rosiglitazone (2 mg) exposure parameters, maximum plasma concentration and the area under the concentration-time curve, or pharmacokinetic parameter, elimination half-life when coadministered with ISIS 113715. Furthermore, there was no effect of ISIS 113715, administered in combination with metformin, on the urinary excretion of metformin. Conversely, there were no observed alterations in ISIS 113715 pharmacokinetics when administered in combination with any of the oral antidiabetic compounds. These data provide evidence that ISIS 113715 exhibits no clinically relevant pharmacokinetic interactions on the disposition and clearance of the oral antidiabetic drugs. The results of these studies support further study of ISIS 113715 in combination with antidiabetic compounds.

Glucose dysregulation and response to common anti-diabetic agents in the FATZO/Pco mouse.

PubMed

Peterson, Richard G; Jackson, Charles Van; Zimmerman, Karen M; Alsina-Fernandez, Jorge; Michael, M Dodson; Emmerson, Paul J; Coskun, Tamer

2017-01-01

The FATZO/Pco mouse is the result of a cross of the C57BL/6J and AKR/J strains. The crossing of these two strains and the selective inbreeding for obesity, insulin resistance and hyperglycemia has resulted in an inbred strain exhibiting obesity in the presumed presence of an intact leptin pathway. Routinely used rodent models for obesity and diabetes research have a monogenic defect in leptin signaling that initiates obesity. Given that obesity and its sequelae in humans are polygenic in nature and not associated with leptin signaling defects, the FATZO mouse may represent a more translatable rodent model for study of obesity and its associated metabolic disturbances. The FATZO mouse develops obesity spontaneously when fed a normal chow diet. Glucose intolerance with increased insulin levels are apparent in FATZO mice as young as 6 weeks of age. These progress to hyperglycemia/pre-diabetes and frank diabetes with decreasing insulin levels as they age. The disease in these mice is multi-faceted, similar to the metabolic syndrome apparent in obese individuals, and thus provides a long pre-diabetic state for determining the preventive value of new interventions. We have assessed the utility of this new model for the pre-clinical screening of agents to stop or slow progression of the metabolic syndrome to severe diabetes. Our assessment included: 1) characterization of the spontaneous development of disease, 2) comparison of metabolic disturbances of FATZO mice to control mice and 3) validation of the model with regard to the effectiveness of current and emerging anti-diabetic agents; rosiglitazone, metformin and semaglutide. Male FATZO mice spontaneously develop significant metabolic disease when compared to normal controls while maintaining hyperglycemia in the presence of high leptin levels and hyperinsulinemia. The disease condition responds to commonly used antidiabetic agents.

Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus and Effect of DPP-4 Inhibitor Treatment on ADA Activity.

PubMed

Lee, Jae-Geun; Kang, Dong Gu; Yu, Jung Re; Kim, Youngree; Kim, Jinsoek; Koh, Gwanpyo; Lee, Daeho

2011-04-01

Dipeptidyl peptidase 4 (DPP-4, also known as CD26) binds with adenosine deaminase (ADA) to activate T lymphocytes. Here, we investigated whether ADA activity is specifically affected by treatment with DPP-4 inhibitor (DPP4I) compared with other anti-diabetic agents. Fasting ADA activity, in addition to various metabolic and biochemical parameters, were measured in 262 type 2 diabetes mellitus (T2DM) patients taking various anti-diabetic agents and in 46 non-diabetic control subjects. ADA activity was increased in T2DM patients compared with that in non-diabetic control subjects (mean±standard error, 23.1±0.6 U/L vs. 18.6±0.8 U/L; P<0.05). ADA activity was correlated with fasting plasma glucose (r=0.258, P<0.05), HbA1c (r=0.208, P<0.05), aspartate aminotransferase (r=0.325, P<0.05), and alanine aminotransferase (r=0.248, P<0.05). Compared with the well-controlled T2DM patients (HbA1c<7%), the poorly controlled group (HbA1c>9%) showed significantly increased ADA activity (21.1±0.8 U/L vs. 25.4±1.6 U/L; P<0.05). The effect of DPP4I on ADA activity in T2DM patients did not differ from those of other oral anti-diabetic agents or insulin. T2DM patients on metformin monotherapy showed a lower ADA activity (20.9±1.0 U/L vs. 28.1±2.8 U/L; P<0.05) compared with that of those on sulfonylurea monotherapy. Our results show that ADA activity is increased in T2DM patients compared to that in non-diabetic patients, is positively correlated with blood glucose level, and that DPP4I has no additional specific effect on ADA activity, except for a glycemic control- or HbA1c-dependent effect.

Xylitol improves pancreatic islets morphology to ameliorate type 2 diabetes in rats: a dose response study.

PubMed

Rahman, Md Atiar; Islam, Md Shahdiul

2014-07-01

Xylitol has been reported as a potential antidiabetic sweetener in a number of recent studies; however, the most effective dietary dose and organ-specific effects are still unclear. Six-week-old male Sprague-Dawley rats were randomly divided into 5 groups: normal control (NC), diabetic control (DBC), diabetic xylitol 2.5% (DXL2.5), diabetic xylitol 5.0% (DXL5), and diabetic xylitol 10.0% (DXL10). Diabetes was induced only in the animals in DBC and DXL groups and considered diabetic when their nonfasting blood glucose level was >300 mg/dL. The DXL groups were fed with 2.5%, 5.0%, and 10% xylitol solution, whereas the NC and DBC groups were supplied with normal drinking water. After 4-wk intervention, body weight, food and fluid intake, blood glucose, serum fructosamine, liver glycogen, serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, creatine kinase, uric acid, creatinine, and most serum lipids were significantly decreased, and serum insulin concentration, glucose tolerance ability, and pancreatic islets morphology were significantly improved in the DXL10 group compared to the DBC group. The data of this study suggest that 10% xylitol has the better antidiabetic effects compared to 2.5% and 5.0% and it can be used as an excellent antidiabetic sweetener and food supplement in antidiabetic foods. Xylitol is widely used as a potential anticariogenic and sweetening agent in a number of oral care and food products when many of its health benefits are still unknown. Due to its similar sweetening power but lower calorific value (2.5 compared with 4 kcal) and lower glycemic index (13 compared with 65) compared to sucrose, recently it has been widely used as a sugar substitute particularly by overweight, obese, and diabetic patients in order to reduce their calorie intake from sucrose. However, the potential antidiabetic effects of xylitol have been discovered recently. The results of this study confirmed the effective dietary dose of xylitol for diabetics with some of the mechanisms of actions behind its antidiabetic effects. © 2014 Institute of Food Technologists®

Effect of bromocriptine-QR on glycemic control in subjects with uncontrolled hyperglycemia on one or two oral anti-diabetes agents.

PubMed

Vinik, Aaron I; Cincotta, Anthony H; Scranton, Richard E; Bohannon, Nancy; Ezrokhi, Michael; Gaziano, J Michael

2012-01-01

To investigate the effect of Bromocriptine-QR on glycemic control in patients with type 2 diabetes whose glycemia is poorly controlled on one or two oral anti-diabetes agents. Five hundred fifteen Type 2 Diabetes Mellitus (T2DM) subjects (ages 18 to 80 and average body mass index [BMI] of 32.7) with baseline HbA1c ≥ 7.5 and on one or two oral anti-diabetes (OAD) medications (metformin, sulfonylurea, and/or thiazolidinediones) were randomized 2:1 to bromocriptine-QR (1.6 to 4.8 mg/day) or placebo for a 24 week treatment period. Study investigators were allowed to adjust, if necessary, subject anti-diabetes medications during the study to attempt to achieve glycemic control in case of glycemic deterioration. The impact of bromocriptine-QR treatment intervention on glycemic control was assessed in subjects on any one or two OADs (ALL treatment category) (N = 515), or on metformin with or without another OAD (Met/OAD treatment category) (N = 356), or on metformin plus a sulfonylurea (Met/SU treatment category) (N = 245) 1) by examining the between group difference in change from baseline a) concomitant OAD medication changes during the study, and b) HbA1c and 2) by determining the odds of reaching HbA1c of ≤ 7.0% on bromocriptine-QR versus placebo. Significantly more patients (approximately 1.5 to 2-fold more; P<.05) intensified concomitant anti-diabetes medication therapy during the study in the placebo versus the bromocriptine-QR arm. In subjects that did not change the intensity of the baseline diabetes therapy (72%), and that were on any one or two OADs (ALL), or on metformin with or without another OAD (Met/OAD), or on metformin plus sulfonylurea (Met/SU), the HbA1c change for bromocriptine-QR versus placebo was -0.47 versus +0.22 (between group delta of -0.69, P<.0001), -0.55 versus +0.26 (between group delta of -0.81, P<.0001) and -0.63 versus +0.20 (between group delta of -0.83, P<.0001) respectively, after 24 weeks on therapy. The odds ratio of reaching HbA1c of ≤ 7.0% was 6.50, 12.03 and 11.45 (P<.0002) for these three groups, respectively. In T2DM subjects whose hyperglycemia is poorly controlled on one or two oral agents, bromocriptine-QR therapy for 24 weeks can provide significant added improvement in glycemic control relative to adding placebo.

Preservative effect of electrolyzed reduced water on pancreatic beta-cell mass in diabetic db/db mice.

PubMed

Kim, Mi-Ja; Jung, Kyung Hee; Uhm, Yoon Kyung; Leem, Kang-Hyun; Kim, Hye Kyung

2007-02-01

Oxidative stress is produced under diabetic conditions and involved in progression of pancreatic beta-cell dysfunction. Both an increase in reactive oxygen free radical species (ROS) and a decrease in the antioxidant defense mechanism lead to the increase in oxidative stress in diabetes. Electrolyzed reduced water (ERW) with ROS scavenging ability may have a potential effect on diabetic animals, a model for high oxidative stress. Therefore, the present study examined the possible anti-diabetic effect of ERW in genetically diabetic mouse strain C57BL/6J-db/db (db/db). ERW with ROS scavenging ability reduced the blood glucose concentration, increased blood insulin level, improved glucose tolerance and preserved beta-cell mass in db/db mice. The present data suggest that ERW may protects beta-cell damage and would be useful for antidiabetic agent.

Insulin-releasing action of the novel antidiabetic agent BTS 67 582.

PubMed

McClenaghan, N H; Flatt, P R; Bailey, C J

1998-02-01

1. BTS 67582 (1,1-dimethyl-2-(2-morpholinophenyl)guanidine fumarate) is a novel antidiabetic agent with a short-acting insulin-releasing effect. This study examined its mode of action in the clonal B-cell line BRIN-BD11. 2. BTS 67582 increased insulin release from BRIN-BD11 cells in a concentration-dependent manner (10[-8] to 10[-4] M) at both non-stimulating (1.1 mM) and stimulating (16.7 mM) concentrations of glucose. 3. BTS 67582 (10[-4] M) potentiated the insulin-releasing effect of a depolarizing concentration of K+ (30 mM), whereas the K+ channel openers pinacidil (400 microM) and diazoxide (300 microM) inhibited BTS 67582-induced release. 4. Suppression of Ca+ channel activity with verapamil (20 microM) reduced the insulin-releasing effect of BTS 67582 (10[-4] M). 5. BTS 67582 (10[-4] M) potentiated insulin release induced by amino acids (10 mM), and enhanced the combined stimulant effects of glucose plus either the fatty acid palmitate (10 mM), or agents which raise intracellular cyclic AMP concentrations (25 microM forskolin and 1 mM isobutylmethylxanthine), or the cholinoceptor agonist carbachol (100 microM). 6. Inhibition of glucose-stimulated insulin release by adrenaline or noradrenaline (10 microM) was partially reversed by BTS 67582 (10[-4] M). 7. These data suggest that the insulin-releasing effect of BTS 67582 involves regulation of ATP-sensitive K+ channel activity and Ca2+ influx, and that the drug augments the stimulant effects of nutrient insulin secretagogues and agents which enhance adenylate cyclase and phospholipase C. BTS 67582 may also exert insulin-releasing effects independently of ATP-sensitive K+ channel activity.

Terbinafine-induced lichenoid drug eruption.

PubMed

Zheng, Yue; Zhang, Jie; Chen, Haiyan; Lai, Wei; Maibach, Howard I

2017-03-01

Drug-induced lichen planus has been induced by antibiotics, anticonvulsants, antidiabetics, antimalarials, antitubercular drugs, antihypertensives, psychiatric drugs, chemotherapeutic agents, diuretic, heavy metals, NSAIDs, etc. Terbinafine, an antifungal agent, is widely used for dermatophyte infections and onychomycosis. Cutaneous adverse effects of terbinafine are rarely reported. Here, we report a case of terbinafine-induced lichenoid drug eruption in a 22-year-old who presented with generalized lichenoid eruption 2 weeks after terbinafine initiation of. The body and lip cleared completely after 8 weeks of drug withdrawal; nail change cleared after 12 weeks.

Antidiabetic and antihyperlipidemic activity of Piper longum root aqueous extract in STZ induced diabetic rats

PubMed Central

2013-01-01

Background The available drugs for diabetes, Insulin or Oral hypoglycemic agents have one or more side effects. Search for new antidiabetic drugs with minimal or no side effects from medicinal plants is a challenge according to WHO recommendations. In this aspect, the present study was undertaken to evaluate the antihyperglycemic and antihyperlipidemic effects of Piper longum root aqueous extract (PlrAqe) in streptozotocin (STZ) induced diabetic rats. Methods Diabetes was induced in male Wister albino rats by intraperitoneal administration of STZ (50 mg/kg.b.w). Fasting blood glucose (FBG) levels were measured by glucose-oxidase & peroxidase reactive strips. Serum biochemical parameters such as glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol were estimated. The activities of liver and kidney functional markers were measured. The statistical analysis of results was carried out using Student t-test and one-way analysis (ANOVA) followed by DMRT. Results During the short term study the aqueous extract at a dosage of 200 mg/kg.b.w was found to possess significant antidiabetic activity after 6 h of the treatment. The administration of aqueous extract at the same dose for 30 days in STZ induced diabetic rats resulted in a significant decrease in FBG levels with the corrections of diabetic dyslipidemia compared to untreated diabetic rats. There was a significant decrease in the activities of liver and renal functional markers in diabetic treated rats compared to untreated diabetic rats indicating the protective role of the aqueous extract against liver and kidney damage and its non-toxic property. Conclusions From the above results it is concluded that the plant extract is capable of managing hyperglycemia and complications of diabetes in STZ induced diabetic rats. Hence this plant may be considered as one of the potential sources for the isolation of new oral anti hypoglycemic agent(s). PMID:23414307

Cardiovascular effects of anti-diabetes drugs

PubMed Central

Younk, Lisa M.; Lamos, Elizabeth M.

2016-01-01

Introduction Cardiovascular disease remains the major contributor to morbidity and mortality in diabetes. From the need to reduce cardiovascular risk in diabetes and to ensure that such risk is not exacerbated by drug treatments, governmental regulators and drug manufacturers have focused on clinical trials evaluating cardiovascular outcomes. Areas covered Findings from mechanistic and clinical trials of biguanides, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose transporter 2 (SGLT-2) inhibitors will be reviewed. These drug classes will be compared within the context of available cardiovascular outcomes data. Clinical implications of new study regulations will be examined. Expert opinion Recent cardiovascular studies provide a more comprehensive evaluation of specific anti-diabetes therapy in individuals with high cardiovascular risk. Long-term effects of anti-hyperglycemic agents in patients with lower cardiovascular risk are still speculative. Historical data supports continued use of metformin as a first-line agent. DPP-4 inhibitors and GLP-1 receptor agonists appear to have neutral effects on cardiovascular outcomes. The significantly decreased cardiovascular risk associated with empagliflozin SGLT-2 inhibitor therapy is impressive and may change how practitioners prescribe add-on therapy to metformin. PMID:27268470

Relation between diabetes, metformin treatment and the occurrence of malignancies in a Belgian primary care setting.

PubMed

Geraldine, Ngwana; Marc, Aerts; Carla, Truyers; Chantal, Mathieu; Stefaan, Bartholomeeusen; Welcome, Wami; Frank, Buntinx

2012-08-01

Associations between type 2 diabetic patients and a higher risk of developing cancer have been reported worldwide. Recently, a protective effect of metformin has been described. To examine in the Belgian primary care population the relation between presence of type 2 diabetes with and without metformin treatment and the occurrence of malignancies. Retrospective cohort study, based on the Intego database, an ongoing Belgian general practice-based morbidity registry, covering 90 general practitioners and including about 1.5 million patient-years between 1994 and 2008. Cox proportional hazard analysis comparing emergence of malignancy in patients with and without type 2 diabetes, and among patients with diabetes comparing emergence of malignancy in those treated with various antidiabetic drugs. Malignancies occurred more in type 2 diabetic patients compared to non-diabetic controls (HR=1.84; 95% CI=1.51-2.24), adjusted for age, gender and weight. Treatment with both metformin and 'other' antidiabetic agents was related to decreased cancer risk (HR=0.24 and 0.22) compared to diet only in men but not in women. In this Belgian primary care setting, diabetic patients have higher cancer prevalences than non-diabetic patients. Moreover, in diabetic men, not only metformin but also other antidiabetic agents were associated with lower cancer risks. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Antidiabetic effect of polyphenolic extracts from selected edible plants as α-amylase, α -glucosidase and PTP1B inhibitors, and β pancreatic cells cytoprotective agents - a comparative study.

PubMed

Zakłos-Szyda, Małgorzata; Majewska, Iwona; Redzynia, Małgorzata; Koziołkiewicz, Maria

2015-01-01

Type 2 diabetes mellitus, which is usually a result of wrong dietary habits and reduced physical activity, represents 85-95% of all diabetes cases and among other diet related diseases is the major cause of deaths. The disease is characterized mainly by hyperglycemia, which is associated with attenuated insulin sensitivity or beta cells dysfunction caused by multiple stimuli, including oxidative stress and loss of insulin secretion. Since polyphenols possess multiple biological activities and constitute an important part of the human diet, they have recently emerged as critical phytochemicals in type 2 diabetes prevention and treatment. Their hypoglycemic action results from their antioxidative effect involved in recovering of altered antioxidant defenses and restoring insulin secreting machinery in pancreatic cells, or abilities to inhibit the activity of carbohydrates hydrolyzing enzymes (α-amylase and α-glucosidase) or protein tyrosine phosphatase 1B (PTP1B), which is known as the major negative regulator in insulin signaling. This study investigates the total phenolic content (Folin-Ciocalteu and HPLC methods) and antioxidant capacity (ABTS) of 20 polyphenolic extracts obtained from selected edible plants, which were screened in terms of α -amylase, α - glucosidase and protein tyrosine phosphatase 1B inhibitors or protective agents against oxidative stress induced by tertbutylhydroperoxide (t-BOOH) in βTC3 pancreatic beta cells used as a model target for antidiabetes drugs. The study concludes that Chaenomeles japonica, Oenothera paradoxa and Viburnum opulus may be promising natural sources for active compounds with antidiabetic properties.

A Retrospect Study on Thiazole Derivatives as the Potential Antidiabetic Agents in Drug Discovery & Developments.

PubMed

Khatik, Gopal L; Datusalia, Ashok Kumar; Ahsan, Waquar; Kaur, Paranjeet; Vyas, Manish; Mittal, Amit; Nayak, Surendra Kumar

2017-09-15

Heterocycles containing thiazole, a moiety with sulfur and nitrogen is a core structure which found in a number of biologically active compounds. The thiazole ring is notable as a component of the certain natural products, such as vitamin B1 (thiamine) and penicillins. Thiazole is also known as wonder nucleus and has versatile in different biological fields. A number of new compounds contain heterocycle thiazole moieties, thus it is one of the important areas of research. We searched the scientific database using relevant keywords. Among the searched literature only peer-reviewed papers were collected which addresses our questions. The retrieved quality research articles were screened and analyzed critically. The key findings of these studies were included along with their importance. The quality research articles included in this review, were selected for the life-threatening diseases i.e. diabetes, which is one of the serious issues all over the globe with an estimated worldwide prevalence in 2016 of 422 million people, which is expected to rise double by 2030. Since 1995, there has been an explosion of the introduction of new classes of pharmacological agents having thiazole moieties. However, most of the drugs can cause noncompliance, hypoglycemia, and obesity. Thus new antidiabetic drugs with thiazole moieties came up with improved compliance and reduced side effects such as pioglitazone (Actos), rosiglitazone (Avandia), netoglitazone, DRF-2189, PHT46, PMT13, DRF-2519. With such a great importance, research in thiazole is part of many academic and industrial laboratories worldwide. The present review describes the importance of thiazole nucleus and its derivatives as antidiabetic agents with an emphasis on the past as well as recent developments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Antidiabetic and Antioxidant Impacts of Desert Date (Balanites aegyptiaca) and Parsley (Petroselinum sativum) Aqueous Extracts: Lessons from Experimental Rats.

PubMed

Abou Khalil, Nasser S; Abou-Elhamd, Alaa S; Wasfy, Salwa I A; El Mileegy, Ibtisam M H; Hamed, Mohamed Y; Ageely, Hussein M

2016-01-01

Medicinal plants are effective in controlling plasma glucose level with minimal side effects and are commonly used in developing countries as an alternative therapy for the treatment of type 1 diabetes mellitus. The aim of this study is to evaluate the potential antidiabetic and antioxidant impacts of Balanites aegyptiaca and Petroselinum sativum extracts on streptozotocin-induced diabetic and normal rats. The influences of these extracts on body weight, plasma glucose, insulin, total antioxidant capacity (TAC), malondialdehyde (MDA) levels, and liver-pyruvate kinase (L-PK) levels were assessed. Furthermore, the weight and histomorphological changes of the pancreas were studied in the different experimental groups. The herbal preparations significantly reduced the mean plasma glucose and MDA levels and significantly increased the mean plasma insulin, L-PK, and TAC levels in the treated diabetic groups compared to the diabetic control group. An obvious increase in the weight of the pancreas and the size of the islets of Langerhans and improvement in the histoarchitecture were evident in the treated groups compared to untreated ones. In conclusion, the present study provides a scientific evidence for the traditional use of these extracts as antidiabetic and antioxidant agents in type 1 diabetes mellitus.

Glucose dysregulation and response to common anti-diabetic agents in the FATZO/Pco mouse

PubMed Central

Jackson, Charles Van; Zimmerman, Karen M.; Alsina-Fernandez, Jorge; Michael, M. Dodson; Emmerson, Paul J.; Coskun, Tamer

2017-01-01

The FATZO/Pco mouse is the result of a cross of the C57BL/6J and AKR/J strains. The crossing of these two strains and the selective inbreeding for obesity, insulin resistance and hyperglycemia has resulted in an inbred strain exhibiting obesity in the presumed presence of an intact leptin pathway. Routinely used rodent models for obesity and diabetes research have a monogenic defect in leptin signaling that initiates obesity. Given that obesity and its sequelae in humans are polygenic in nature and not associated with leptin signaling defects, the FATZO mouse may represent a more translatable rodent model for study of obesity and its associated metabolic disturbances. The FATZO mouse develops obesity spontaneously when fed a normal chow diet. Glucose intolerance with increased insulin levels are apparent in FATZO mice as young as 6 weeks of age. These progress to hyperglycemia/pre-diabetes and frank diabetes with decreasing insulin levels as they age. The disease in these mice is multi-faceted, similar to the metabolic syndrome apparent in obese individuals, and thus provides a long pre-diabetic state for determining the preventive value of new interventions. We have assessed the utility of this new model for the pre-clinical screening of agents to stop or slow progression of the metabolic syndrome to severe diabetes. Our assessment included: 1) characterization of the spontaneous development of disease, 2) comparison of metabolic disturbances of FATZO mice to control mice and 3) validation of the model with regard to the effectiveness of current and emerging anti-diabetic agents; rosiglitazone, metformin and semaglutide. Conclusion: Male FATZO mice spontaneously develop significant metabolic disease when compared to normal controls while maintaining hyperglycemia in the presence of high leptin levels and hyperinsulinemia. The disease condition responds to commonly used antidiabetic agents. PMID:28640857

Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus and Effect of DPP-4 Inhibitor Treatment on ADA Activity

PubMed Central

Lee, Jae-Geun; Kang, Dong Gu; Yu, Jung Re; Kim, Youngree; Kim, Jinsoek; Koh, Gwanpyo

2011-01-01

Background Dipeptidyl peptidase 4 (DPP-4, also known as CD26) binds with adenosine deaminase (ADA) to activate T lymphocytes. Here, we investigated whether ADA activity is specifically affected by treatment with DPP-4 inhibitor (DPP4I) compared with other anti-diabetic agents. Methods Fasting ADA activity, in addition to various metabolic and biochemical parameters, were measured in 262 type 2 diabetes mellitus (T2DM) patients taking various anti-diabetic agents and in 46 non-diabetic control subjects. Results ADA activity was increased in T2DM patients compared with that in non-diabetic control subjects (mean±standard error, 23.1±0.6 U/L vs. 18.6±0.8 U/L; P<0.05). ADA activity was correlated with fasting plasma glucose (r=0.258, P<0.05), HbA1c (r=0.208, P<0.05), aspartate aminotransferase (r=0.325, P<0.05), and alanine aminotransferase (r=0.248, P<0.05). Compared with the well-controlled T2DM patients (HbA1c<7%), the poorly controlled group (HbA1c>9%) showed significantly increased ADA activity (21.1±0.8 U/L vs. 25.4±1.6 U/L; P<0.05). The effect of DPP4I on ADA activity in T2DM patients did not differ from those of other oral anti-diabetic agents or insulin. T2DM patients on metformin monotherapy showed a lower ADA activity (20.9±1.0 U/L vs. 28.1±2.8 U/L; P<0.05) compared with that of those on sulfonylurea monotherapy. Conclusion Our results show that ADA activity is increased in T2DM patients compared to that in non-diabetic patients, is positively correlated with blood glucose level, and that DPP4I has no additional specific effect on ADA activity, except for a glycemic control- or HbA1c-dependent effect. PMID:21738897

SGLT2 inhibitors to control glycemia in type 2 diabetes mellitus: a new approach to an old problem.

PubMed

Jabbour, Serge A

2014-01-01

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with a novel insulin-independent mechanism of action. The SGLT2 is a transporter found in the proximal tubule of the kidney and is responsible for approximately 90% of renal glucose reabsorption. The SGLT2 inhibitors reduce reabsorption of glucose in the kidney, resulting in glucose excretion in the urine (50-90 g of ~180 g filtered by the kidneys daily), which in turn lowers plasma glucose levels in people with diabetes. The insulin-independent mechanism of action of SGLT2 inhibitors dictates that they are associated with a very low risk of hypoglycemia and can be used in patients with any degree of β-cell function or insulin sensitivity. Clinical trials have shown that SGLT2 inhibitors are effective at reducing blood glucose levels, body weight, and blood pressure when used as monotherapy or in combination with other antidiabetic agents in patients with type 2 diabetes mellitus. Treatment with SGLT2 inhibitors is generally well tolerated, although these agents have been associated with an increased incidence of genital infections. The SGLT2 inhibitors have become a valuable addition to the armory of drugs used to treat patients with type 2 diabetes mellitus, and several agents within the class are currently under investigation in phase III clinical trials.

Glucose supply and insulin demand dynamics of antidiabetic agents.

PubMed

Monte, Scott V; Schentag, Jerome J; Adelman, Martin H; Paladino, Joseph A

2010-03-01

For microvascular outcomes, there is compelling historical and contemporary evidence for intensive blood glucose reduction in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). There is also strong evidence to support macrovascular benefit with intensive blood glucose reduction in T1DM. Similar evidence remains elusive for T2DM. Because cardiovascular outcome trials utilizing conventional algorithms to attain intensive blood glucose reduction have not demonstrated superiority to less aggressive blood glucose reduction (Action to Control Cardiovascular Risk in Diabetes; Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; and Veterans Affairs Diabetes Trial), it should be considered that the means by which the blood glucose is reduced may be as important as the actual blood glucose. By identifying quantitative differences between antidiabetic agents on carbohydrate exposure (CE), hepatic glucose uptake (HGU), hepatic gluconeogenesis (GNG), insulin resistance (IR), peripheral glucose uptake (PGU), and peripheral insulin exposure (PIE), we created a pharmacokinetic/pharmacodynamic model to characterize the effect of the agents on the glucose supply and insulin demand dynamic. Glucose supply was defined as the cumulative percentage decrease in CE, increase in HGU, decrease in GNG, and decrease in IR, while insulin demand was defined as the cumulative percentage increase in PIE and PGU. With the glucose supply and insulin demand effects of each antidiabetic agent summated, the glucose supply (numerator) was divided by the insulin demand (denominator) to create a value representative of the glucose supply and insulin demand dynamic (SD ratio). Alpha-glucosidase inhibitors (1.25), metformin (2.20), and thiazolidinediones (TZDs; 1.25-1.32) demonstrate a greater effect on glucose supply (SD ratio >1), while secretagogues (0.69-0.81), basal insulins (0.77-0.79), and bolus insulins (0.62-0.67) demonstrate a greater effect on insulin demand (SD ratio <1). Alpha-glucosidase inhibitors, metformin, and TZDs demonstrate a greater effect on glucose supply, while secretagogues, basal insulin, and bolus insulin demonstrate a greater effect on insulin demand. Because T2DM cardiovascular outcome trials have not demonstrated macrovascular benefit with more aggressive blood glucose reduction when using conventional algorithms that predominantly focus on insulin demand, it would appear logical to consider a model that incorporates both the extent of blood glucose lowering (hemoglobin A1c) and the means by which the blood glucose was reduced (SD ratio) when considering macrovascular outcomes. (c) 2010 Diabetes Technology Society.

Chalcones and their therapeutic targets for the management of diabetes: structural and pharmacological perspectives.

PubMed

Mahapatra, Debarshi Kar; Asati, Vivek; Bharti, Sanjay Kumar

2015-03-06

Diabetes Mellitus (DM) is the fastest growing metabolic disorder affecting about 387 million people across the globe and is estimated to affect 592 million people by year 2030. The search for newer anti-diabetic agents is the foremost need to control the accelerating diabetic population. Several natural and (semi) synthetic chalcones deserve the credit of being potential candidates that act by modulating the therapeutic targets PPAR-γ, DPP-4, α-glucosidase, PTP1B, aldose reductase, and stimulate insulin secretion and tissue sensitivity. In this review, a comprehensive study (from January 1977 to October 2014) of anti-diabetic chalcones, their molecular targets, structure activity relationships (SARs), mechanism of actions (MOAs) and patents have been described. The compounds which showed promising activity and have a well-defined MOAs, SARs must be considered as prototype for the design and development of potential anti-diabetic agents. They should be evaluated critically at all clinical stages to ensure their therapeutic and toxicological profile to meet the demand of diabetics. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Synthesis of (+)-Antroquinonol: An Antihyperglycemic Agent.

PubMed

Sulake, Rohidas S; Lin, Hsiao-Han; Hsu, Chia-Yu; Weng, Ching-Feng; Chen, Chinpiao

2015-06-19

The total synthesis of antroquinonol has been accomplished through Suzuki-Miyaura cross-coupling and Barton-McCombie reaction, and the α,β-unsaturation was achieved through selenylation and oxidation protocols. In vitro and in vivo studies on the glucose-lowering properties of antroquinonol indicate that it is a potential antidiabetic agent.

Antidiabetic and anticancer activities of Mangifera indica cv. Okrong leaves

PubMed Central

Ganogpichayagrai, Aunyachulee; Palanuvej, Chanida; Ruangrungsi, Nijsiri

2017-01-01

Diabetes and cancer are a major global public health problem. Plant-derived agents with undesirable side-effects were required. This study aimed to evaluate antidiabetic and anticancer activities of the ethanolic leaf extract of Mangifera indica cv. Okrong and its active phytochemical compound, mangiferin. Antidiabetic activities against yeast α-glucosidase and rat intestinal α-glucosidase were determined using 1 mM of p-nitro phenyl-α-D-glucopyranoside as substrate. Inhibitory activity against porcine pancreatic α-amylase was performed using 1 mM of 2-chloro-4 nitrophenol-α-D-maltotroside-3 as substrate. Nitrophenol product was spectrophotometrically measured at 405 nm. Anticancer activity was evaluated against five human cancer cell lines compared to two human normal cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Mango leaf extract and mangiferin exhibited dose-dependent inhibition against yeast α-glucosidase with the IC50 of 0.0503 and 0.5813 mg/ml, respectively, against rat α-glucosidase with the IC50 of 1.4528 and 0.4333 mg/ml, respectively, compared to acarbose with the IC50 of 11.9285 and 0.4493 mg/ml, respectively. For anticancer activity, mango leaf extract, at ≥200 μg/ml showed cytotoxic potential against all tested cancer cell lines. In conclusion, mango leaf possessed antidiabetic and anticancer potential in vitro. PMID:28217550

Antidiabetic Mechanisms of Rosa canina Fruits

PubMed Central

Fattahi, Ali; Niyazi, Fatemeh; Shahbazi, Behzad; Farzaei, Mohammad Hosein; Bahrami, Gholamreza

2016-01-01

Rosa canina fruits have been used traditionally for the treatment of diabetes mellitus and its complications. The aim of current study was to evaluate the in vitro mechanism of action of R canina in managing diabetes mellitus. Cell proliferation and cytotoxicity assay were performed on pancreatic β-cells, βTC6. The protective activity of the extract on streptozotocin-induced death in βTC6 cells was studied. The effect of R canina on the metabolism of glucose in HepG2, a hepatocellular carcinoma cell line, was evaluated. The effect of the extract on glucose diffusion across the dialysis membrane, which is a comfortable model for assessing cellular glucose absorption, was evaluated. The results obtained from current study confirmed that R canina extract can act as a growth factor for pancreatic β-cell line providing a novel mechanism for the observed antidiabetic effect of this natural agent. Further preclinical studies are necessary to evaluate the perfect mechanism of action of R canina in diabetes mellitus. PMID:27352916

Antidiabetic and Antioxidant Impacts of Desert Date (Balanites aegyptiaca) and Parsley (Petroselinum sativum) Aqueous Extracts: Lessons from Experimental Rats

PubMed Central

Abou Khalil, Nasser S.; Abou-Elhamd, Alaa S.; Wasfy, Salwa I. A.; El Mileegy, Ibtisam M. H.; Hamed, Mohamed Y.; Ageely, Hussein M.

2016-01-01

Medicinal plants are effective in controlling plasma glucose level with minimal side effects and are commonly used in developing countries as an alternative therapy for the treatment of type 1 diabetes mellitus. The aim of this study is to evaluate the potential antidiabetic and antioxidant impacts of Balanites aegyptiaca and Petroselinum sativum extracts on streptozotocin-induced diabetic and normal rats. The influences of these extracts on body weight, plasma glucose, insulin, total antioxidant capacity (TAC), malondialdehyde (MDA) levels, and liver-pyruvate kinase (L-PK) levels were assessed. Furthermore, the weight and histomorphological changes of the pancreas were studied in the different experimental groups. The herbal preparations significantly reduced the mean plasma glucose and MDA levels and significantly increased the mean plasma insulin, L-PK, and TAC levels in the treated diabetic groups compared to the diabetic control group. An obvious increase in the weight of the pancreas and the size of the islets of Langerhans and improvement in the histoarchitecture were evident in the treated groups compared to untreated ones. In conclusion, the present study provides a scientific evidence for the traditional use of these extracts as antidiabetic and antioxidant agents in type 1 diabetes mellitus. PMID:27019854

Sodium-Glucose linked transporter 2 (SGLT2) inhibitors--fighting diabetes from a new perspective.

PubMed

Angelopoulos, Theodoros P; Doupis, John

2014-06-01

Sodium-Glucose linked transporter 2 (SGLT2) inhibitors are a new family of antidiabetic pharmaceutical agents whose action is based on the inhibition of the glucose reabsorption pathway, resulting in glucosuria and a consequent reduction of the blood glucose levels, in patients with type 2 diabetes mellitus. Apart from lowering both fasting and postprandial blood glucose levels, without causing hypoglycemia, SGLT2 inhibitors have also shown a reduction in body weight and the systolic blood pressure. This review paper explores the renal involvement in glucose homeostasis providing also the latest safety and efficacy data for the European Medicines Agency and U.S. Food and Drug Administration approved SGLT2 inhibitors, looking, finally, into the future of this novel antidiabetic category of pharmaceutical agents.

Synthesis and biological evaluation of novel gigantol derivatives as potential agents in prevention of diabetic cataract

USDA-ARS?s Scientific Manuscript database

As a continuation of our efforts directed towards the development of natural anti-diabetic cataract agents, gigantol was isolated from Herba dendrobii and was found to inhibit both aldose reductase (AR) and inducible nitric oxide synthase (iNOS) activity, which play a significant role in the develop...

The treatment of diabetes mellitus of patients with chronic liver disease.

PubMed

García-Compeán, Diego; González-González, José A; Lavalle-González, Fernando J; González-Moreno, Emmanuel I; Maldonado-Garza, Héctor J; Villarreal-Pérez, Jesús Zacarías

2015-01-01

About 80% of patients with liver cirrhosis may have glucose metabolism disorders, 30% show overt diabetes mellitus (DM). Prospective studies have demonstrated that DM is associated with an increased risk of hepatic complications and death in patients with liver cirrhosis. DM might contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochondrial oxidative stress mediated by adipokines. Based on the above mentioned the effective control of hyperglycemia may have a favorable impact on the evolution of these patients. However, only few therapeutic studies have evaluated the effectiveness and safety of antidiabetic drugs and the impact of the treatment of DM on morbidity and mortality in patients with liver cirrhosis. In addition, oral hypoglycemic agents and insulin may produce hypoglycemia and lactic acidosis, as most of these agents are metabolized by the liver. This review discusses the clinical implications of DM in patients with chronic liver disease. In addition the effectiveness and safety of old, but particularly the new antidiabetic drugs will be described based on pharmacokinetic studies and chronic administration to patients. Recent reports regarding the use of the SGLT2 inhibitors as well as the new incretin-based therapies such as injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral inhibitors of dipeptidylpeptidase-4 (DPP-4) will be discussed. The establishment of clear guidelines for the management of diabetes in patients with CLD is strongly required.

Evaluation of antihyperglycemic activity of Cocos nucifera Linn. on streptozotocin induced type 2 diabetic rats.

PubMed

Naskar, Sagar; Mazumder, Upal K; Pramanik, Goutam; Gupta, Malaya; Kumar, R B Suresh; Bala, Asis; Islam, Aminul

2011-12-08

The plant Cocos nucifera Linn. (Arecaceae) is commonly known as coconut. Traditionally the juice of the young spadix when fresh is used in diarrhea and diabetes. The objective of the present study was to investigate the effect of antidiabetic activity and effect on lipid profile as well as cardioprotective effect of hydro-methanol extract of Cocos nucifera (HECN) on streptozotocin (STZ)-induced diabetic rats. After 72 h of STZ (50 mg/kg, b.w. i.p.) administration, animals showing plasma sugar level more than 250 mg/dl were considered as diabetic rat. Fasting blood glucose (FBG) levels were measured on 0th (after 72 h of STZ), 5th, 10th, and 15th day. On the 15th day all the animals were sacrificed and the serum biochemical parameters and antioxidant enzyme status were measured. HECN treated animals showed a significant reduction in FBG level as compared with diabetic control group. Serum enzyme level (SGOT, SGPT, SALP), lipid peroxidation and antioxidant enzyme level such as CAT, GSH, SOD and cholesterol and triglycerides in the HECN treated groups were restored towards normal level as compared to diabetic control groups and the values were comparable with the standard groups (glibenclamide). Improvement in the FBG and the restoration of all other biomarker as well as enzymes indicates that HECN has very good antidiabetic activity with very low side effects and provides a scientific rationale for the use as an antidiabetic agent. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Evaluation of Antioxidant, Antidiabetic and Anticholinesterase Activities of Smallanthus sonchifolius Landraces and Correlation with Their Phytochemical Profiles

PubMed Central

Russo, Daniela; Valentão, Patrícia; Andrade, Paula B.; Fernandez, Eloy C.; Milella, Luigi

2015-01-01

The present study aimed to investigate the phytochemical profile of leaf methanol extracts of fourteen Smallanthus sonchifolius (yacon) landraces and their antioxidant, anticholinesterase and antidiabetic activities that could lead to the finding of more effective agents for the treatment and management of Alzheimer’s disease and diabetes. For this purpose, antioxidant activity was assessed using different tests: ferric reducing ability power (FRAP), 2,2-diphenyl-1-picryl hydrazyl (DPPH), nitric oxide (˙NO) and superoxide (O2˙−) scavenging and lipid peroxidation inhibition assays. Anticholinesterase activity was investigated by quantifying the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, whereas antidiabetic activity was investigated by α-amylase and α-glucosidase inhibition tests. To understand the contribution of metabolites, phytochemical screening was also performed by high performance liquid chromatography-diode array detector (HPLC-DAD) system. Among all, methanol extract of PER09, PER04 and ECU44 landraces exhibited the highest relative antioxidant capacity index (RACI). ECU44 was found to be rich in 4,5-di-O-caffeoylquinic acid (CQA) and 3,5-di-O-CQA and displayed a good α-amylase and α-glucosidase inhibition, showing the lowest IC50 values. Flavonoids, instead, seem to be involved in the AChE and BChE inhibition. The results of this study revealed that the bioactive compound content differences could be determinant for the medicinal properties of this plant especially for antioxidant and antidiabetic activities. PMID:26263984

Evaluation of Antioxidant, Antidiabetic and Anticholinesterase Activities of Smallanthus sonchifolius Landraces and Correlation with Their Phytochemical Profiles.

PubMed

Russo, Daniela; Valentão, Patrícia; Andrade, Paula B; Fernandez, Eloy C; Milella, Luigi

2015-07-31

The present study aimed to investigate the phytochemical profile of leaf methanol extracts of fourteen Smallanthus sonchifolius (yacon) landraces and their antioxidant, anticholinesterase and antidiabetic activities that could lead to the finding of more effective agents for the treatment and management of Alzheimer's disease and diabetes. For this purpose, antioxidant activity was assessed using different tests: ferric reducing ability power (FRAP), 2,2-diphenyl-1-picryl hydrazyl (DPPH), nitric oxide (˙NO) and superoxide (O2˙-) scavenging and lipid peroxidation inhibition assays. Anticholinesterase activity was investigated by quantifying the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, whereas antidiabetic activity was investigated by α-amylase and α-glucosidase inhibition tests. To understand the contribution of metabolites, phytochemical screening was also performed by high performance liquid chromatography-diode array detector (HPLC-DAD) system. Among all, methanol extract of PER09, PER04 and ECU44 landraces exhibited the highest relative antioxidant capacity index (RACI). ECU44 was found to be rich in 4,5-di-O-caffeoylquinic acid (CQA) and 3,5-di-O-CQA and displayed a good α-amylase and α-glucosidase inhibition, showing the lowest IC50 values. Flavonoids, instead, seem to be involved in the AChE and BChE inhibition. The results of this study revealed that the bioactive compound content differences could be determinant for the medicinal properties of this plant especially for antioxidant and antidiabetic activities.

Adverse Effects Associated With Newer Diabetes Therapies.

PubMed

Akiyode, Oluwaranti F; Adesoye, Adebola A

2017-04-01

The increasing number of newer type 2 diabetes therapies has allowed providers an increased armamentarium for the optimal management of patients with diabetes. In fact, these newer agents have unique benefits in the management of type 2 diabetes. However, they are also associated with certain adverse effects. This review article aims to describe the notable adverse effects of these newer antidiabetic therapies including the glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and the sodium-glucose cotransporter 2 inhibitors. The adverse effects reviewed herein include pancreatitis, medullary thyroid carcinoma, heart failure, gastrointestinal disturbances, renal impairment, and genitourinary infections. More clinical data are necessary to solidify the association of some of these adverse effects with the newer diabetes agents. However, it is important for health care practitioners to be well informed and prepared to properly monitor patients for these adverse effects.

Pharmacological Modulation of Lung Carcinogenesis in Smokers: Preclinical and Clinical Evidence

PubMed Central

De Flora, Silvio; Ganchev, Gancho; Iltcheva, Marietta; La Maestra, Sebastiano; Micale, Rosanna T.; Steele, Vernon E.; Balansky, Roumen

2016-01-01

Many drugs in common use possess pleiotropic properties that make them capable of interfering with carcinogenesis mechanisms. We discuss here the ability of pharmacological agents to mitigate the pulmonary carcinogenicity of mainstream cigarette smoke. The evaluated agents included antiinflammatory drugs (budesonide, celecoxib, aspirin, naproxen, licofelone), antidiabetic drugs (metformin, pioglitazone), antineoplastic agents (lapatinib, bexarotene, vorinostat), and other drugs and supplements (phenethyl isothiocyanate, myo-inositol, N-acetylcysteine, ascorbic acid, berry extracts). The drugs have been evaluated in mouse models mimicking interventions either in current smokers or in ex-smokers or a prenatal chemoprevention. They displayed a broad spectrum of activities by attenuating either smoke-induced preneoplastic lesions or benign tumors and/or malignant tumors. Together with epidemiological data, these findings provide useful information to predict the potential effects of pharmacological agents in smokers. PMID:26726119

Anti-diabetic properties of flavonoid compounds isolated from Hyphaene thebaica epicarp on alloxan induced diabetic rats

PubMed Central

Salib, Josline Y.; Michael, Helana N.; Eskande, Emad Fawzy

2013-01-01

Background: Diabetes mellitus, becoming the third killer of mankind after cancer and cardiovascular diseases, is one of the most challenging diseases facing health care professionals today. That is why; there has been a growing interest in the therapeutic use of natural products for diabetes, especially those derived from plants. Aim: To evaluate the anti-diabetic activity together with the accompanying biological effects of the fractions and the new natural compounds of Hyphaene thebaica (HT) epicarp. Materials and Methods: 500 g of coarsely powdered of (HT) fruits epicarp were extracted by acetone. The acetone crude extract was fractionated with methanol and ethyl acetate leaving a residual water-soluble fraction WF. The anti-diabetic effects of the WF and one of its compounds of the acetone extract of the (HT) epicarp were investigated in this study using 40 adult male rats. Results: Phytochemical investigation of active WF revealed the presence of ten different flavonoids, among which two new natural compounds luteolin 7-O-[6”-O-α-Lrhamnopyranosyl]-β-D-galactopyranoside 3 and chrysoeriol 7-O-β-D-galactopyranosyl(1→2)-α-L-arabinofuranoside 5 were isolated. Supplementation of the WF improved glucose and insulin tolerance and significantly lowered blood glycosylated hemoglobin levels. On the other hand, compound 5 significantly reduced AST and ALT levels of liver, respectively. Likewise, the kidney functions were improved for both WF and compound 5, whereby both urea and creatinine levels in serum were highly significant Conclusion: The results justify the use of WF and compound 5 of the (HT) epicarp as anti-diabetic agent, taking into consideration that the contents of WF were mainly flavonoids PMID:23598921

Antidiabetic Effects of Aqueous Infusions of Artemisia herba-alba and Ajuga iva in Alloxan-Induced Diabetic Rats.

PubMed

Boudjelal, Amel; Siracusa, Laura; Henchiri, Cherifa; Sarri, Madani; Abderrahim, Benkhaled; Baali, Faiza; Ruberto, Giuseppe

2015-06-01

The aqueous infusions of the aerial parts of Artemisia herba-alba Asso and Ajuga iva Schreber, prepared in accordance with the traditional procedure used in the local folk medicine, have been analysed for their composition and content of phytochemical constituents and examined for their antidiabetic effectiveness in alloxan-induced diabetic rats. Oral administration of A. herba-alba and A. iva infusions was studied in normal and alloxan-induced diabetic rats, which were randomly divided into nine groups, each group consisting of six animals. The drug preparations (100, 200, and 300 mg/kg b. w.) of each plant were given orally to the rats of each group twice daily for 15 days. Compositional analysis of the aqueous infusions revealed the presence of several polyphenols as main components. A. herba-alba infusion was characterised by mono- and di-cinnamoylquinic acids, with 5-caffeoylquinic (chlorogenic) acid being the main compound, followed by 3,5-dicaffeoylquinic acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant among flavonoids. On the other hand, A. iva showed the exclusive presence of flavonoids, with the flavanone naringin present in relatively high levels together with several apigenin (flavone) derivatives. Oral administration of 300 mg/kg b. w. of the aqueous infusions of A. herba-alba and A. iva exhibited a significant reduction in blood glucose content, showing a much more efficient antidiabetic activity compared to glibenclamide, the oral hypoglycaemic agent used as a positive control in this study. These results suggest that A. herba-alba and A. iva possess significant antidiabetic activity, as they were able to improve the biochemical damage in alloxan-induced diabetes in rats. Georg Thieme Verlag KG Stuttgart · New York.

The significance of compliance and persistence in the treatment of diabetes, hypertension and dyslipidaemia: a review

PubMed Central

Cramer, J A; Benedict, Á; Muszbek, N; Keskinaslan, A; Khan, Z M

2008-01-01

Objectives To review studies of patient compliance/persistence with cardiovascular or antidiabetic medication published since the year 2000; to compare the methods used to measure compliance/persistence across studies; to compare reported compliance/persistence rates across therapeutic classes and to assess whether compliance/persistence correlates with clinical outcomes. Methods English language papers published between January 2000 and November 2005 investigating patient compliance/persistence with cardiovascular or antidiabetic medication were identified through searches of the MEDLINE and EMBASE databases. Definitions and measurements of compliance/persistence were compared across therapeutic areas using contingency tables. Results Of the 139 studies analysed, 32% focused on hypertension, 27% on diabetes and 13% on dyslipidaemia. The remainder covered coronary heart disease and cardiovascular disease (CVD) in general. The most frequently reported measure of compliance was the 12-month medication possession ratio (MPR). The overall mean MPR was 72%, and the MPR did not differ significantly between treatment classes (range: 67–76%). The average proportion of patients with an MPR of > 80% was 59% overall, 64% for antihypertensives, 58% for oral antidiabetics, 51% for lipid-lowering agents and 69% in studies of multiple treatments, again with no significant difference between treatment classes. The average 12-month persistence rate was 63% and was similar across therapeutic classes. Good compliance had a positive effect on outcome in 73% of the studies examining clinical outcomes. Conclusions Non-compliance with cardiovascular and antidiabetic medication is a significant problem, with around 30% of days ‘on therapy’ not covered by medication and only 59% of patients taking medication for more than 80% of their days ‘on therapy’ in a year. Good compliance has a positive effect on clinical outcome, suggesting that the management of CVD may be improved by improving patient compliance. PMID:17983433

Antihyperglycaemic effect of Mangifera indica in rat.

PubMed

Aderibigbe, A O; Emudianughe, T S; Lawal, B A

1999-09-01

The leaves of Mangifera indica are used as an antidiabetic agent in Nigerian folk medicine. To determine whether or not there is a scientific basis for this use, the effect of the aqueous extract of the leaves on blood glucose level was assessed in normoglycaemic, glucose - induced hyperglycaemic and streptozotocin (STZ)-induced diabetic rats. The aqueous extract given orally (1 g/kg) did not alter the blood glucose levels in either normoglycaemic or STZ-induced diabetic rats. In glucose - induced hyperglycaemia, however, antidiabetic activity was seen when the extract and glucose were administered simultaneously and also when the extract was given to the rats 60 min before the glucose. The hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide (200 mg/kg) under the same conditions. The results of this study indicate that the aqueous extract of the leaves of Mangifera indica possess hypoglycaemic activity. This action may be due to an intestinal reduction of the absorption of glucose. However, other different mechanisms of action cannot be excluded. Copyright 1999 John Wiley & Sons, Ltd.

Ursolic acid derivatives as potential antidiabetic agents: In vitro, in vivo, and in silico studies.

PubMed

Guzmán-Ávila, Ricardo; Flores-Morales, Virginia; Paoli, Paolo; Camici, Guido; Ramírez-Espinosa, Juan José; Cerón-Romero, Litzia; Navarrete-Vázquez, Gabriel; Hidalgo-Figueroa, Sergio; Yolanda Rios, Maria; Villalobos-Molina, Rafael; Estrada-Soto, Samuel

2018-03-01

Hit, Lead & Candidate Discovery Protein tyrosine phosphatase 1B (PTP-1B) has attracted interest as a novel target for the treatment of type 2 diabetes, this because its role in the insulin-signaling pathway as a negative regulator. Thus, the aim of current work was to obtain seven ursolic acid derivatives as potential antidiabetic agents with PTP-1B inhibition as main mechanism of action. Furthermore, derivatives 1-7 were submitted in vitro to enzymatic PTP-1B inhibition being 3, 5, and 7 the most active compounds (IC 50  = 5.6, 4.7, and 4.6 μM, respectively). In addition, results were corroborated with in silico docking studies with PTP-1B orthosteric site A and extended binding site B, showed that 3 had polar and Van der Waals interactions in both sites with Lys120, Tyr46, Ser216, Ala217, Ile219, Asp181, Phe182, Gln262, Val49, Met258, and Gly259, showing a docking score value of -7.48 Kcal/mol, being more specific for site A. Moreover, compound 7 showed polar interaction with Gln262 and Van der Waals interactions with Ala217, Phe182, Ile219, Arg45, Tyr46, Arg47, Asp48, and Val49 with a predictive docking score of -6.43 kcal/mol, suggesting that the potential binding site could be localized in the site B adjacent to the catalytic site A. Finally, derivatives 2 and 7 (50 mg/kg) were selected to establish their in vivo antidiabetic effect using a noninsulin-dependent diabetes mice model, showing significant blood glucose lowering compared with control group (p < .05). © 2018 Wiley Periodicals, Inc.

Adenosine monophosphate-activated protein kinase-based classification of diabetes pharmacotherapy

PubMed Central

Dutta, D; Kalra, S; Sharma, M

2017-01-01

The current classification of both diabetes and antidiabetes medication is complex, preventing a treating physician from choosing the most appropriate treatment for an individual patient, sometimes resulting in patient-drug mismatch. We propose a novel, simple systematic classification of drugs, based on their effect on adenosine monophosphate-activated protein kinase (AMPK). AMPK is the master regular of energy metabolism, an energy sensor, activated when cellular energy levels are low, resulting in activation of catabolic process, and inactivation of anabolic process, having a beneficial effect on glycemia in diabetes. This listing of drugs makes it easier for students and practitioners to analyze drug profiles and match them with patient requirements. It also facilitates choice of rational combinations, with complementary modes of action. Drugs are classified as stimulators, inhibitors, mixed action, possible action, and no action on AMPK activity. Metformin and glitazones are pure stimulators of AMPK. Incretin-based therapies have a mixed action on AMPK. Sulfonylureas either inhibit AMPK or have no effect on AMPK. Glycemic efficacy of alpha-glucosidase inhibitors, sodium glucose co-transporter-2 inhibitor, colesevelam, and bromocriptine may also involve AMPK activation, which warrants further evaluation. Berberine, salicylates, and resveratrol are newer promising agents in the management of diabetes, having well-documented evidence of AMPK stimulation medicated glycemic efficacy. Hence, AMPK-based classification of antidiabetes medications provides a holistic unifying understanding of pharmacotherapy in diabetes. This classification is flexible with a scope for inclusion of promising agents of future. PMID:27652986

Ipragliflozin and other sodium-glucose cotransporter-2 (SGLT2) inhibitors in the treatment of type 2 diabetes: preclinical and clinical data.

PubMed

Kurosaki, Eiji; Ogasawara, Hideaki

2013-07-01

Sodium-glucose cotransporter-2 (SGLT2) is expressed in the proximal tubules of the kidneys and plays a key role in renal glucose reabsorption. A novel class of antidiabetic medications, SGLT2-selective inhibitors attempt to improve glycemic control in diabetics by preventing glucose from being reabsorbed through SGLT2 and re-entering circulation. Ipragliflozin is an SGLT2 inhibitor in Phase 3 clinical development for the treatment of type 2 diabetes mellitus (T2DM). In this review, we summarize recent animal and human studies on ipragliflozin and other SGLT2 inhibitors including dapagliflozin, canagliflozin, empagliflozin, tofogliflozin, and luseogliflozin. These agents all show potent and selective SGLT2 inhibition in vitro and reduce blood glucose levels and HbA1c in both diabetic animal models and patients with T2DM. SGLT2 inhibitors offer several advantages over other classes of hypoglycemic agents. Due to their insulin-independent mode of action, SGLT2 inhibitors provide steady glucose control without major risk for hypoglycemia and may also reverse β-cell dysfunction and insulin resistance. Other favorable effects of SGLT2 inhibitors include a reduction in both body weight and blood pressure. SGLT2 inhibitors are safe and well tolerated and can easily be combined with other classes of antidiabetic medications to achieve tighter glycemic control. The long-term safety and efficacy of these agents are under evaluation. Copyright © 2013 Elsevier Inc. All rights reserved.

Metformin inhibits goitrogenous effects of type 2 diabetes.

PubMed

Ittermann, Till; Markus, Marcello R P; Schipf, Sabine; Derwahl, Michael; Meisinger, Christa; Völzke, Henry

2013-07-01

Data on the association between type 2 diabetes mellitus (T2DM) and thyroid volume are sparse. An experimental study demonstrated an inhibitory effect of metformin on the growth of human thyroid cells. So far no study on humans has investigated potentially modulating effects of metformin on the association between T2DM and thyroid volume. Therefore, we investigated these effects in a population-based cohort study. We used data from the Study of Health in Pomerania and included 2570 individuals for cross-sectional and 1088 individuals for longitudinal analyses. T2DM was defined by physician-diagnosed self-report or intake of antidiabetic medication. In the cross-sectional data, females with T2DM treated with antidiabetic medication other than metformin had a larger thyroid volume (β=4.69; 95% CI 1.87 to 7.50) and a higher odds ratio (OR) for goiter (OR=1.71; 95% CI 1.05 to 2.79) than females without T2DM, whereas in males, no such association was detected. In females or males treated with metformin, T2DM was not associated with thyroid volume or goiter. In longitudinal analyses, incident T2DM not treated with metformin was significantly associated with a higher risk for incident goiter in the total population (incidence rate ratio (IRR)=1.70; 95% CI 1.10 to 2.91). Individuals with T2DM having changed from metformin to other antidiabetic agents during follow-up also had a higher risk for incident goiter than individuals without T2DM (IRR=2.71; 95% CI 1.74 to 4.20). We demonstrate an inhibitory effect of metformin on prevalent and incident goiter. Anti-goitrogenous effects of metformin add to the general benefits of metformin treatment of T2DM.

Glipizide. A review of the pharmacoeconomic implications of the extended-release formulation in type 2 diabetes mellitus.

PubMed

Foster, R H; Plosker, G L

2000-09-01

Glipizide is a second generation sulphonylurea agent that is available in a Gastrointestinal Therapeutic System (GITS) extended-release formulation. Glipizide GITS provides more stable plasma drug concentrations than the immediate-release formulation and the once-daily regimen may optimise patient compliance. In patients with type 2 diabetes mellitus, glipizide GITS is at least as effective as the immediate-release formulation of glipizide in providing glycaemic control, and may have a greater effect on fasting plasma glucose levels. Any therapeutic advantage over other antidiabetic agents remains to be established, but in a preliminary report (n = 40) glipizide GITS provided better glycaemic control and produced less fasting insulinaemia than glibenclamide (glyburide). The incidence of hypoglycaemic symptoms with glipizide GITS is low (< or = 3%). Quality of life was improved compared with baseline after 12 weeks' treatment with glipizide GITS 5 to 20 mg/day plus diet in a US double-blind, placebo-controlled trial in 569 patients with type 2 diabetes mellitus. Hyperglycaemic symptom-related distress decreased with glipizide GITS treatment, while hypoglycaemic symptom-related distress was not significantly increased compared with placebo plus diet. Quality of life during glipizide GITS treatment has not been compared with that during treatment with other antidiabetic agents. Monthly productivity losses related to absenteeism were $US91 (1995 values) per patient lower in the glipizide GITS group compared with the placebo group in the latter prospective study. Productivity parameters improved slightly or did not change significantly in the glipizide GITS group, but deteriorated in the placebo group. Differences in direct healthcare costs between groups were small and not comprehensively reported. Glipizide GITS was the least costly strategy for first-line therapy in a US cost-of-treatment model of the first 3 years after diagnosis of type 2 diabetes mellitus. The total per-patient cost was $US4867 with glipizide GITS, $US5196 with metformin and $US5249 with acarbose (1996/1997 values). Monthly drug acquisition costs were lower, and glycosylated haemoglobin levels and patient compliance were improved, after formulary conversion from the immediate-release to the GITS formulation of glipizide in a US single-hospital retrospective analysis. Glipizide GITS produced better cost outcomes than metformin and acarbose in a model of 3 years' treatment of type 2 diabetes mellitus. Glipizide GITS had pharmacoeconomic and quality of life advantages over diet alone in the short term, but more clinically relevant comparisons with other antidiabetic agents are needed. There are limitations to the present data, but the available pharmacoeconomic data have been favourable for glipizide GITS.

Use of glucagon-like peptide-1 receptor agonists and bone fractures: a meta-analysis of randomized clinical trials.

PubMed

Mabilleau, Guillaume; Mieczkowska, Aleksandra; Chappard, Daniel

2014-05-01

Patients with type 2 diabetes mellitus (T2DM) are at a higher risk of bone fractures independent of the use of antidiabetic medications. Furthermore, antidiabetic medications could directly affect bone metabolism. Recently, the use of dipeptidyl peptidase-4 inhibitors has been associated with a lower rate of bone fracture. The aim of the present meta-analysis was to assess whether patients with T2DM treated with glucagon-like peptide-1 receptor agonists (GLP-1Ra) present a lower incidence of bone fracture compared with patients using other antidiabetic drugs. A search on Medline, Embase, and http://www.clinicaltrials.gov, as well as a manual search for randomized clinical trials of T2DM treated with either a GLP-1Ra or another antidiabetic drug for a duration of ≥24 weeks was conducted by two authors (GM, AM) independently. Although 28 eligible studies were identified, only seven trials reported the occurrence of at least a bone fracture in one arm of the trial. The total number of fractures was 19 (13 and six with GLP-1Ra and comparator, respectively). The pooled Mantel-Haenszel odds ratio for GLP-1Ra was 0.75 (95% confidence interval 0.28-2.02, P = 0.569) in trials versus other antidiabetic agents. Although preliminary, our study highlighted that the use of GLP-1Ra does not modify the risk of bone fracture in T2DM compared with the use of other antidiabetic medications. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Phytochemicals and antidiabetic activity of Eusideroxylon zwageri stem bark collected from East Kalimantan, Indonesia

NASA Astrophysics Data System (ADS)

Kusuma, I. W.; Rahmini; Ramadhan, R.; Rahmawati, N.; Suwasono, R. A.; Sari, NM

2018-04-01

Eusideroxylon zwagery (Lauraceae), a tropical tree species known as ulin or borneo iron wood and traditionally used for the treatment of diabetes in the Ethnic of Kutai. Plant extract was prepared by maceration using ethanol. The plant extract was evaluated its DPPH and superoxide radicals scavenging activity, the inhibition on α-glucosidase and α-amylase activity as antidiabetic potential and the analysis of the total phenolic, total flavonoids and proanthocyanidin contents. The ethanolic extract of the stem bark was 8.62% on the dry weight basis. The IC50 values of antioxidant activity of the extract in DPPH and superoxide radical scavenging mechanisms were 44.90 µg/ml and 30.47 µg/ml. In antidiabetic assay, the E. zwageri stem bark extract showed IC50 value 58.45µg/ml in ɑ-glucosidase inhibition, and 9.04 µg/ml in ɑ-amylase inhibition. Quercetin, an antidiabetic activity-having flavonoid, displayed IC50 values 2.00 µg/ml and 4.04 µg/ml in ɑ-glucosidase and ɑ-amylase inhibitory assays. In phytochemical assay, the extract had 31.28 GAE/g extract (mg), 30.48 CE/g extract (mg) and 183.3 PE/g extract (mg) for the total phenolic, total flavonoid and total proanthocyanidin contents. The limited reports of E. zwageri indicated the needs to search the active compounds from plant as potential antidiabetic agents by considering plant conservation status.

Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment.

PubMed

Peláez-Jaramillo, Maria J; Cárdenas-Mojica, Allison A; Gaete, Paula V; Mendivil, Carlos O

2018-04-01

Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM. A diagnosis of PLTDM should be established only after doses of CNI and steroids are stable and the post-operative stress has been overcome. The predominant defect induced by CNI is insulin secretory dysfunction. Plasma glucose control must start immediately after the transplant procedure in order to improve long-term results for both patient and transplant. Among the better known antidiabetics, metformin and DPP-4 inhibitors have a particularly benign profile in the PLTDM context and are the preferred oral agents for long-term management. Insulin therapy is also an effective approach that addresses the prevailing pathophysiological defect of the disorder. There is still insufficient evidence about the impact of newer families of antidiabetics (GLP-1 agonists, SGLT-2 inhibitors) on PLTDM. In this review, we summarize current knowledge on the epidemiology, pathogenesis, course of disease and medical management of PLTDM.

Insulin sensitizing and alpha-glucoamylase inhibitory action of sennosides, rheins and rhaponticin in Rhei Rhizoma.

PubMed

Choi, Soo Bong; Ko, Byoung Seob; Park, Seong Kyu; Jang, Jin Sun; Park, Sunmin

2006-01-25

Extracts from Rhei Rhizoma extracts (RR) have been reported to attenuate metabolic disorders such as diabetic nephropathy, hypercholesterolemia and platelet aggregation. With this study we investigated the anti-diabetic action of 70% ethanol RR extract in streptozotocin-induced diabetic mice, and determined the action mechanism of active compounds of RR in vitro. In the diabetic mice, serum glucose levels at fasting and post-prandial states and glucose area under the curve at modified oral glucose tolerance tests were lowered without altering serum insulin levels, indicating that RR contained potential anti-diabetic agents. The fractions fractionated from RR extracts by XAD-4 column revealed that 60%, 80% and 100% methanol fractions enhanced insulin sensitivity and inhibited alpha-glucoamylase activity. The major compounds of these fractions were sennosides, rhein and rhaponticin. Rhaponticin and rhein enhanced insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Rhaponticin increased adipocytes with a differentiating effect similar to pioglitazone, but rhein and sennoside B decreased triglyceride accumulation. Sennoside A and B inhibited alpha-glucoamylase activity as much as acarbose. In conclusion, a crude extract of RR improves glucose intolerance by enhancing insulin-stimulated glucose uptake and decreasing carbohydrate digestion via inhibiting alpha-glucoamylase activity. Rhein and rhaponticin are potential candidates for hypoglycemic agents.

A review of nateglinide in the management of patients with type 2 diabetes

PubMed Central

Tentolouris, Nicholas; Voulgari, Christina; Katsilambros, Nicholas

2007-01-01

Impaired insulin secretion occurs early in the pathogenesis of type 2 diabetes mellitus (T2DM) and is chronic and progressive, resulting initially in impaired glucose tolerance (IGT) and eventually in T2DM. As most patients with T2DM have both insulin resistance and insulin deficiency, therapy for T2DM should aim to control not only fasting, but also postprandial plasma glucose levels. While oral glucose-lowering treatment with metformin and thiazolidinediones corrects fasting plasma glucose, these agents do not address the problem of mealtime glucose spikes that have been shown to trigger atherogenic processes. Nateglinide is a derivative of the amino acid D-phenylalanine, which acts directly on the pancreatic β-cells to stimulate insulin secretion. Nateglinide monotherapy controls significantly mealtime hyperglycemia and results in improved overall glycemic control in patients with T2DM by reducing glycosylated hemoglobin (HbA1c) levels. The combination of nateglinide with insulin-sensitising agents, such as metformin and thiazolidinediones, targets both insulin deficiency and insulin resistance and results in reductions in HbA1c that could not be achieved by monotherapy with other antidiabetic agents. In prediabetic subjects with IGT, nateglinide restores early insulin secretion and reduces postprandial hyperglycemia. Nateglinide has an excellent safety and tolerability profile and provides a lifetime flexibility that other antidiabetic agents could not accomplish. The aim of this review is to identify nateglinide as an effective “gate-keeper” in T2DM, since it restores early-phase insulin secretion and prevents mealtime glucose spikes throughout the day and to evaluate the results of ongoing research into its potential role in delaying the progression to overt diabetes and reducing its complications and mortality. PMID:18200800

In-silico analysis of gymnemagenin from Gymnema sylvestre (Retz.) R.Br. with targets related to diabetes.

PubMed

Rathore, Poonam K; Arathy, V; Attimarad, Vijaylaxmi S; Kumar, Pramod; Roy, Subarna

2016-02-21

Diabetes is a metabolic disorder characterized by higher than normal glucose in the blood. Most oral hypoglycemic drugs available in market produce adverse side effects which have resulted in continued search for new therapeutic agents with little or no side effects. Herbal drugs are considered relatively safer alternatives and Gymnema sylvestre is one of the most well established natural remedy for diabetes and is traded worldwide under several brands. In the present study an attempt has been made to use in silico techniques to understand and predict the drug likeliness of gymnemagenin, one of the key constituents of G. sylvestre against 15 proteins having key role in carbohydrate metabolism. Gymnemagenin was found to dock well with crystallographic structures of 7 of the 15 selected targets and was found even better than the two known clinically used antidiabetic compounds, repaglinide and sitagliptin taken in the study for comparison. Gymnemagenin therefore can be considered further for development into a potent anti-diabetic drug. Copyright © 2015 Elsevier Ltd. All rights reserved.

Emerging Drugs and Indications for Cardio-Metabolic Disorders in People with Severe Mental Illness.

PubMed

Kouidrat, Youssef; Amad, Ali; De Hert, Marc

2015-01-01

Patients with severe mental illnesses, such as schizophrenia and bipolar disorder, are at increased risk of developing metabolic disorders including obesity, diabetes, and dyslipidemia. All of these comorbidities increase the risk of cardiovascular disease and mortality. Different approaches, including diet and lifestyle modifications, behavioral therapy and switching antipsychotic agents, have been proposed to manage these metabolic abnormalities. However, these interventions may be insufficient, impractical or fail to counteract the metabolic dysregulation. Consequently, a variety of pharmacological agents such as antidiabetic drugs, have been studied in an attempt to reverse the weight gain and metabolic abnormalities evident in these patients. Despite a significant effect, many of these treatments are used off-label. This qualitative review focuses on pharmacological agents that could offer significant benefits in the management of cardio-metabolic disorders associated with serious mental illness.

Marine Algae As A Prospective Source For Antidiabetic Compounds - A Brief Review.

PubMed

Unnikrishnan, Pulikkaparambil Sasidharan; Jayasri, Mangalam Achuthananda

2018-01-01

Diabetes Mellitus (DM) is a metabolic disorder characterized by chronic hyperglycaemia, which is attributed to several life threatening complications including atherosclerosis, nephropathy, and retinopathy. The current therapies available for the management of DM mainly include oral antidiabetic drugs and insulin injections. However, continuous use of synthetic drugs provides lower healing with many side effects. Therefore, there is an urge for safe and efficient antidiabetic drugs for the management of DM. In the continuing search for effective antidiabetic drugs, marine algae (seaweeds) remains as a promising source with potent bioactivity. It is anticipated that the isolation, characterization, and pharmacological study of unexplored marine algae can be useful in the discovery of novel antidiabetic compounds with high biomedical value. Among marine algae, brown and red algae are reported to exhibit antidiabetic activity. Majority of the investigations on algal derived compounds controls the blood glucose levels through the inhbition of carbohydrate hydroloyzing enzymes and protein tyrosine phosphatase 1B enzymes, insulin sensitization, glucose uptake effect and other protective effects against diabetic complications. Based on the above perspective this review provides; profiles for various marine algae posessing antidiabetic activity. This study also highlights the therapeutic potential of compounds isolated from marine algae for the effective management of diabetes and its associated complications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus.

PubMed

Vallon, Volker

2015-01-01

The kidneys in normoglycemic humans filter 160-180 g of glucose per day (∼30% of daily calorie intake), which is reabsorbed and returned to the systemic circulation by the proximal tubule. Hyperglycemia increases the filtered and reabsorbed glucose up to two- to three-fold. The sodium glucose cotransporter SGLT2 in the early proximal tubule is the major pathway for renal glucose reabsorption. Inhibition of SGLT2 increases urinary glucose and calorie excretion, thereby reducing plasma glucose levels and body weight. The first SGLT2 inhibitors have been approved as a new class of antidiabetic drugs in type 2 diabetes mellitus, and studies are under way to investigate their use in type 1 diabetes mellitus. These compounds work independent of insulin, improve glycemic control in all stages of diabetes mellitus in the absence of clinically relevant hypoglycemia, and can be combined with other antidiabetic agents. By lowering blood pressure and diabetic glomerular hyperfiltration, SGLT2 inhibitors may induce protective effects on the kidney and cardiovascular system beyond blood glucose control.

Evaluation of antidiabetic effect of total calystegines extracted from Hyoscyamus albus.

PubMed

Bourebaba, Lynda; Saci, Souaad; Touguit, Damia; Gali, Lynda; Terkmane, Schahinez; Oukil, Naima; Bedjou, Fatiha

2016-08-01

Hyoscyamus albus L. (Solanaceae) an old medicinal plant is a rich source of tropane and nortropane alkaloids which confers to this plant a number of very interesting and beneficial therapeutic effects. Calystegines that are polyhydroxylated alkaloids and imino-sugars poccess significant glycosidases inhibitory activities and are therefore good candidats for the treatment of diabetes mellitus. Calystegines extracted from Hyoscyamys albus seeds were tested for teir acute oral toxicity and investigated for their in-vivo antidiabetic effect on Streptozotocine induced diabetes in mice. Calystegines were extracted from the seeds plant using an Ion exchange column; the remaining extract was then administrated orally to mice at several single doses for acute toxicity assay. A dose of 130mg/kg streptozotocine was injected to mice to induce diabetes mellitus, and diabetic mice were treated orally during 20days with 10mg/kg and 20mg/kg calystegines and 20mg/kg glibenclamide as the reference drug. Acute oral toxicity showed that calystegines are not toxic up to a dose of 2000mg/kg with absence of any signs of intoxication and damages in Liver and kidney tissues. The nortropane alkaloids markedly reduced blood glucose levels and lipid parameters of diabetic mice to normal concentrations after 20days of treatment at 10mg/kg and 20mg/kg (p<0.05). Histopathological study of diabetic mice pancreas indicated that calystegines of Hyoscyamus albus have minimized streptozotocine damages on β-cells of islets of langerhans, stimulated β-cells regeneration and improved with this insulin secretion. The findings of this study suggest that calystegines are potent antidiabetic agents with antihyperglicemic and hypolipidemic effects, and a protective fonction on pancreas in streptozotocin induced diabetes in mice. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Phytochemical Compositions and In vitro Assessments of Antioxidant and Antidiabetic Potentials of Fractions from Ehretia cymosa Thonn.

PubMed Central

Ogundajo, Akintayo; Ashafa, Anofi Tom

2017-01-01

Background: Ehretia cymosa Thonn. is a popular medicinal plant used in different parts of West Africa for the treatment of various ailments including diabetes mellitus. Objective: The current study investigates bioactive constituents and in vitro antioxidant and antidiabetic potentials of fractions from extract of E. cymosa. Materials and Methods: Phytochemical investigation and antioxidant assays were carried out using standard procedures. Antidiabetic potential was assessed by evaluating the inhibitory effects of the fractions on the activities of α-amylase and α-glucosidase, while bioactive constituent's identification was carried out using gas chromatography-mass spectrometric (GC-MS) analysis. Results: The phytochemistry tests of the fractions revealed the presence of tannins, phenols, flavonoids, steroids, terpene, alkaloid, and cardiac glycosides. Methanol fraction shows higher phenolic (27.44 mg gallic acid/g) and flavonoid (235.31 mg quercetin/g) contents, while ethyl acetate fraction revealed higher proanthocyanidins (28.31 mg catechin/g). Methanol fraction displayed higher (P < 0.05) 1,1-diphenyl-2-picryl-hydrazyl (0.47 mg/mL), 2,2-azino-bis (3-ethylbenzothiazoline)-6-sulfonic acid (0.49 mg/mL), and hydroxyl radical (0.55 mg/mL) scavenging activities, while ethyl acetate exhibited strong metal chelating (0.61 mg/mL) and superoxide anion (1.68 mg/mL) scavenging activity. Methanol and ethyl acetate fractions displayed higher inhibition (P < 0.05) against α-glucosidase (0.60 mg/mL) and α-amylase (2.11 mg/mL), respectively. Methanol fraction also inhibited α-amylase and α-glucosidase in competitive and noncompetitive modes, respectively. The GC-MS chromatogram of the methanol fraction revealed 24 compounds, which include phytol (1.78%), stearic acid (1.02%), and 2-hexadecyloxirane (34.18%), which are known antidiabetic and antioxidant agents. Conclusion: The results indicate E. cymosa leaves as source of active phytochemicals with therapeutic potentials in the management of diabetes. SUMMARY E. cymosa fractions possess antioxidant and antidiabetic activities. Hence, it is a source of active phytochemicals with therapeutic potentials in the management of diabetesThe high flavonoid, phenolic, and proanthocyanidin contents of fractions from E. cymosa also contribute to its antioxidant and antidiabetic propertiesMethanol fraction of E. cymosa displayed better antidiabetic activities compared to acarbose as revealed by their half maximal inhibitory concentration valuesMethanol fraction of E. cymosa extract contains phytol, hexadecyl oxirane, and stearic acid, which are reported to possess antidiabetic and antioxidant potentials. Abbreviations used: ABTS: 2,2- Azino-bis (3-ethylbenzothiazoline)-6-sulfonic acid, DPPH: 1,1-diphenyl-2-picryl-hydrazyl, PMS: Phenazine methosulfate, NBT: Nitroblue tetrazolium, NADH: Nicotinamide adenine dinucleotide, TCA: Trichloroacetic acid, TBA: Thiobarbituric acid, DNS: Dinitrosalicylic acid. PMID:29142401

Phytochemical Compositions and In vitro Assessments of Antioxidant and Antidiabetic Potentials of Fractions from Ehretia cymosa Thonn.

PubMed

Ogundajo, Akintayo; Ashafa, Anofi Tom

2017-10-01

Ehretia cymosa Thonn. is a popular medicinal plant used in different parts of West Africa for the treatment of various ailments including diabetes mellitus. The current study investigates bioactive constituents and in vitro antioxidant and antidiabetic potentials of fractions from extract of E. cymosa . Phytochemical investigation and antioxidant assays were carried out using standard procedures. Antidiabetic potential was assessed by evaluating the inhibitory effects of the fractions on the activities of α-amylase and α-glucosidase, while bioactive constituent's identification was carried out using gas chromatography-mass spectrometric (GC-MS) analysis. The phytochemistry tests of the fractions revealed the presence of tannins, phenols, flavonoids, steroids, terpene, alkaloid, and cardiac glycosides. Methanol fraction shows higher phenolic (27.44 mg gallic acid/g) and flavonoid (235.31 mg quercetin/g) contents, while ethyl acetate fraction revealed higher proanthocyanidins (28.31 mg catechin/g). Methanol fraction displayed higher ( P < 0.05) 1,1-diphenyl-2-picryl-hydrazyl (0.47 mg/mL), 2,2-azino-bis (3-ethylbenzothiazoline)-6-sulfonic acid (0.49 mg/mL), and hydroxyl radical (0.55 mg/mL) scavenging activities, while ethyl acetate exhibited strong metal chelating (0.61 mg/mL) and superoxide anion (1.68 mg/mL) scavenging activity. Methanol and ethyl acetate fractions displayed higher inhibition ( P < 0.05) against α-glucosidase (0.60 mg/mL) and α-amylase (2.11 mg/mL), respectively. Methanol fraction also inhibited α-amylase and α-glucosidase in competitive and noncompetitive modes, respectively. The GC-MS chromatogram of the methanol fraction revealed 24 compounds, which include phytol (1.78%), stearic acid (1.02%), and 2-hexadecyloxirane (34.18%), which are known antidiabetic and antioxidant agents. The results indicate E. cymosa leaves as source of active phytochemicals with therapeutic potentials in the management of diabetes. E. cymosa fractions possess antioxidant and antidiabetic activities. Hence, it is a source of active phytochemicals with therapeutic potentials in the management of diabetesThe high flavonoid, phenolic, and proanthocyanidin contents of fractions from E. cymosa also contribute to its antioxidant and antidiabetic propertiesMethanol fraction of E. cymosa displayed better antidiabetic activities compared to acarbose as revealed by their half maximal inhibitory concentration valuesMethanol fraction of E. cymosa extract contains phytol, hexadecyl oxirane, and stearic acid, which are reported to possess antidiabetic and antioxidant potentials. Abbreviations used: ABTS: 2,2- Azino-bis (3-ethylbenzothiazoline)-6-sulfonic acid, DPPH: 1,1-diphenyl-2-picryl-hydrazyl, PMS: Phenazine methosulfate, NBT: Nitroblue tetrazolium, NADH: Nicotinamide adenine dinucleotide, TCA: Trichloroacetic acid, TBA: Thiobarbituric acid, DNS: Dinitrosalicylic acid.

Fermentation, Isolation, Structure, and antidiabetic activity of NFAT-133 produced by Streptomyces strain PM0324667

PubMed Central

2011-01-01

Type-2 diabetes is mediated by defects in either insulin secretion or insulin action. In an effort to identify extracts that may stimulate glucose uptake, similar to insulin, a high throughput-screening assay for measuring glucose uptake in skeletal muscle cells was established. During the screening studies to discover novel antidiabetic compounds from microbial resources a Streptomyces strain PM0324667 (MTCC 5543, the Strain accession number at Institute of Microbial Technology, Chandigarh, India), an isolate from arid soil was identified which expressed a secondary metabolite that induced glucose uptake in L6 skeletal muscle cells. By employing bioactivity guided fractionation techniques, a tri-substituted simple aromatic compound with anti-diabetic potential was isolated. It was characterized based on MS and 2D NMR spectral data and identified as NFAT-133 which is a known immunosuppressive agent that inhibits NFAT-dependent transcription in vitro. Our investigations revealed the antidiabetic potential of NFAT-133. The compound induced glucose uptake in differentiated L6 myotubes with an EC50 of 6.3 ± 1.8 μM without activating the peroxisome proliferator-activated receptor-γ. Further, NFAT-133 was also efficacious in vivo in diabetic animals and reduced systemic glucose levels. Thus it is a potential lead compound which can be considered for development as a therapeutic for the treatment of type-2 diabetes. We have reported herewith the isolation of the producer microbe, fermentation, purification, in vitro, and in vivo antidiabetic activity of the compound. PMID:22104600

Efficiency of noopept in streptozotocin-induced diabetes in rats.

PubMed

Ostrovskaya, R U; Ozerova, I V; Gudascheva, T A; Kapitsa, I G; Ivanova, E A; Voronina, T A; Seredenin, S B

2013-01-01

We studied the effects of new nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) in various dosage regimens on the dynamics of glycemia, body weight, and pain sensitivity in rats receiving diabetogenic toxin streptozotocin. In experimental diabetic rats, Noopept alleviated glycemia and weight loss and normalized enhanced pain sensitivity. The normalizing effect of Noopept was most pronounced when it was administered as a preventive agent prior to injection of the toxin. Both preventive and therapeutic administration of Noopept (delayed injections included) significantly weakened the examined metabolic effects of diabetogenic toxin. Possible mechanisms of the antidiabetic action of Noopept are analyzed.

Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents

PubMed Central

Fedorova, Elena V.; Buryakina, Anna V.; Zakharov, Alexey V.; Filimonov, Dmitry A.; Lagunin, Alexey A.; Poroikov, Vladimir V.

2014-01-01

Based on the data about structure and antidiabetic activity of twenty seven vanadium and zinc coordination complexes collected from literature we developed QSAR models using the GUSAR program. These QSAR models were applied to 10 novel vanadium coordination complexes designed in silico in order to predict their hypoglycemic action. The five most promising substances with predicted potent hypoglycemic action were selected for chemical synthesis and pharmacological evaluation. The selected coordination vanadium complexes were synthesized and tested in vitro and in vivo for their hypoglycemic activities and acute rat toxicity. Estimation of acute rat toxicity of these five vanadium complexes was performed using a freely available web-resource (http://way2drug.com/GUSAR/acutoxpredict.html). It has shown that the selected compounds belong to the class of moderate toxic pharmaceutical agents, according to the scale of Hodge and Sterner. Comparison with the predicted data has demonstrated a reasonable correspondence between the experimental and predicted values of hypoglycemic activity and toxicity. Bis{tert-butyl[amino(imino)methyl]carbamato}oxovanadium (IV) and sodium(2,2′-Bipyridyl)oxo-diperoxovanadate(V) octahydrate were identified as the most potent hypoglycemic agents among the synthesized compounds. PMID:25057899

Nursing Home Medication Reconciliation: A Quality Improvement Initiative.

PubMed

Tong, Monica; Oh, Hye Young; Thomas, Jennifer; Patel, Sheila; Hardesty, Jennifer L; Brandt, Nicole J

2017-04-01

The current quality improvement initiative evaluated the medication reconciliation process within select nursing homes in Washington, DC. The identification of common types of medication discrepancies through monthly retrospective chart reviews of newly admitted patients in two different nursing homes were described. The use of high-risk medications, namely antidiabetic, anticoagulant, and opioid agents, was also recorded. A standardized spreadsheet tool based on multiple medication reconciliation implementation tool kits was created to record the information. The five most common medication discrepancies were incorrect indication (21%), no monitoring parameters (17%), medication name omitted (11%), incorrect dose (10%), and incorrect frequency (8%). Antidiabetic agents in both sites were the most used high-risk medication. This initiative highlights that medication discrepancies on admission are common in nursing homes and may be clinically impactful. More attention needs to be given to work flow processes to improve medication reconciliation considering the increased risk for adverse drug events and hospitalizations. [Journal of Gerontological Nursing and Mental Health Services, 43(4), 9-14.]. Copyright 2017, SLACK Incorporated.

Phytotherapy in diabetes: Review on potential mechanistic perspectives

PubMed Central

El-Abhar, Hanan S; Schaalan, Mona F

2014-01-01

Diabetes mellitus (DM) is a widely spread epidemic disease that results from the absence of insulin, decreased secretion and/or impaired function. Since DM is a multi-factorial disease, the available pharmaceuticals, despite their sensible treatment, target mostly one pathway to control hyperglycemia and encounter several side effects. Therefore, new therapeutic paradigms aim to hit several pathways using only one agent. Traditionally, antidiabetic plants and/or their active constituents may fulfill this need. More than 200 species of plants possess antidiabetic properties which were evaluated mostly by screening tests without digging far for the exact mode of action. Searching among the different literature resources and various database and in view of the above aspects, the present article provides a comprehensive review on the available antidiabetic plants that have been approved by pharmacological and clinical evaluations, and which their mechanism(s) of action is assured. These plants are categorized according to their proved mode of action and are classified into those that act by inhibiting glucose absorption from intestine, increasing insulin secretion from the pancreas, inhibiting glucose production from hepatocytes, or enhancing glucose uptake by adipose and muscle tissues. The current review also highlights those that mimic in their action the new peptide analogs, such as exenatide, liraglutide and dipeptidylpeptidase-4 inhibitors that increase glucagon-like peptide-1 serum concentration and slow down the gastric emptying. PMID:24748931

Recommendations on the effect of antidiabetic drugs in bone.

PubMed

Rozas-Moreno, Pedro; Reyes-García, Rebeca; Jódar-Gimeno, Esteban; Varsavsky, Mariela; Luque-Fernández, Inés; Cortés-Berdonces, María; Muñoz-Torres, Manuel

2017-03-01

To provide recommendations on the effect of antidiabetic drugs on bone fragility to help select the most adequate antidiabetic treatment, especially in diabetic patients with high risk of fracture. Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. The GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) was used to establish both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each antidiabetic drug: AND "osteoporosis", "fractures", "bone mineral density", "bone markers", "calciotropic hormones". Papers in English with publication date before 30 April 2016 were reviewed. Recommendations were jointly discussed by the Working Group. The document summaries the data on the potential effects of antidiabetic drugs on bone metabolism and fracture risk. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

[Constitutional syndrome associated to metformin induced hepatotoxicity].

PubMed

de la Poza Gómez, Gema; Rivero Fernández, Miguel; Vázquez Romero, Manuel; Angueira Lapeña, Teresa; Arranz de la Mata, Gemma; Boixeda de Miquel, Daniel

2008-12-01

Metformin is an oral antidiabetic agent frequently used to manage type II diabetes. This drug produces nonspecific gastrointestinal symptoms in 5-20% of patients and, more rarely, has also been associated with severe adverse effects such as lactic acidosis. Only a few isolated cases of hepatotoxicity due to this drug have been documented. We report the case of an 83-year-old man with constitutional syndrome and hepatic biochemical alterations, which were attributed to metformin after ruling out an oncologic etiology and observing complete clinical and biochemical resolution after withdrawal of the drug.

Anti-diabetic potential of the essential oil of Pinus koraiensis leaves toward streptozotocin-treated mice and HIT-T15 pancreatic β cells.

PubMed

Joo, Hye-Eun; Lee, Hyo-Jung; Sohn, Eun Jung; Lee, Min-Ho; Ko, Hyun-Suk; Jeong, Soo-Jin; Lee, Hyo-Jeong; Kim, Sung-Hoon

2013-01-01

The metabolic syndrome creates risk factors for coronary heart disease, diabetes, fatty liver, obesity and several cancers. Our group has already reported that the essential oil from leaves of Pinus koraiensis SIEB (EOPK) exerted antihyperlipidemic effects by upregulating the low-density lipoprotein receptor and inhibiting acyl-coenzyme A, cholesterol acyltransferases. We evaluated in the current study the anti-diabetic effects of EOPK on mice with streptozotocin (STZ)-induced type I diabetes and on HIT-T15 pancreatic β cells. EOPK significantly protected HIT-T15 cells from STZ-induced cytotoxicity and reduced the blood glucose level in STZ-induced diabetic mice when compared with the untreated control. EOPK consistently and significantly suppressed the α-amylase activity in a dose-dependent manner and enhanced the expression of insulin at the mRNA level in STZ-treated HIT-T15 cells, while the expression of insulin was attenuated. EOPK also significantly abrogated the population of reactive oxygen species when compared to the untreated control in STZ-treated HIT-T15 cells. Furthermore, EOPK significantly reduce nitric oxide production, suppressed the phosphorylation of endothelial nitric oxide (NO) synthase and suppressed the production of vascular endothelial growth factor (VEGF) in STZ-treated HIT-T15 cells, implying its potential application to diabetic retinopathy. Overall, our findings suggest that EOPK had hypoglycemic potential by inhibiting reactive oxygene species (ROS), endothelial NO synthase (eNOS) and VEGF in STZ-treated mice and HIT-T15 pancreatic β cells as a potent anti-diabetic agent.

Induced desensitization of the insulinotropic effects of antidiabetic drugs, BTS 67 582 and tolbutamide.

PubMed

McClenaghan, N H; Ball, A J; Flatt, P R

2000-05-01

Acute and chronic mechanisms of action of novel insulinotropic antidiabetic drug, BTS 67 582 (1, 1-dimethyl-2-(2-morpholinophenyl)guanidine fumarate), were examined in the stable cultured BRIN-BD11 cell line. BTS 67 582 (100 - 400 microM) stimulated a concentration-dependent increase (P<0.01) in insulin release at both non-stimulatory (1.1 mM) and stimulatory (8. 4 mM) glucose. Long-term exposure (3 - 18 h) to 100 microM BTS 67 582 in culture time-dependently decreased subsequent responsiveness to acute challenge with 200 microM BTS 67 582 or 200 microM tolbutamide at 12 - 18 h (P<0.001). Similarly 3 - 18 h culture with the sulphonylurea, tolbutamide (100 microM), also effectively suppressed subsequent insulinotropic responses to both BTS 67 582 and tolbutamide. Culture with 100 microM BTS 67 582 or 100 microM tolbutamide did not affect basal insulin secretion, cellular insulin content, or cell viability and exerted no influence on the secretory responsiveness to 200 microM of the imidazoline, efaroxan. While 18 h BTS 67 582 culture did not affect the insulin-releasing actions (P<0.001) of 16.7 mM glucose, 10 mM arginine, 30 mM KCl, 25 microM forskolin or 10 nM phorbol-12-myristate 13-acetate (PMA), significant inhibition (P<0.001) of the insulinotropic effects of 10 mM 2-ketoisocaproic acid (KIC) and 10 mM alanine were observed. These data suggest that BTS 67 582 shares a common signalling pathway to sulphonylurea but not imidazoline drugs. Desensitization of drug action may provide an important approach to dissect sites of action of novel and established insulinotropic antidiabetic agents.

New insights into the ameliorative effects of ferulic acid in pathophysiological conditions.

PubMed

Ghosh, Sumit; Basak, Priyanka; Dutta, Sayanta; Chowdhury, Sayantani; Sil, Parames C

2017-05-01

Ferulic acid, a natural phytochemical has gained importance as a potential therapeutic agent by virtue of its easy commercial availability, low cost and minimal side-effects. It is a derivative of curcumin and possesses the necessary pharmacokinetic properties to be retained in the general circulation for several hours. The therapeutic effects of ferulic acid are mediated through its antioxidant and anti-inflammatory properties. It exhibits different biological activities such as anti-inflammatory, anti-apoptotic, anti-carcinogenic, anti-diabetic, hepatoprotective, cardioprotective, neuroprotective actions, etc. The current review addresses its therapeutic effects under different pathophysiological conditions (eg. cancer, cardiomyopathy, skin disorders, brain disorders, viral infections, diabetes etc.). Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of antidiabetic drugs on the incidence of macrovascular complications and mortality in type 2 diabetes mellitus: a new perspective on sodium-glucose co-transporter 2 inhibitors.

PubMed

Rahelić, Dario; Javor, Eugen; Lucijanić, Tomo; Skelin, Marko

2017-02-01

Elevated hemoglobin A 1c (HbA 1c ) values correlate with microvascular and macrovascular complications. Thus, patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing macrovascular events. Treatment of T2DM should be based on a multifactorial approach because of its evidence regarding reduction of macrovascular complications and mortality in T2DM. It is well known that intensive glucose control reduces the risk of microvascular complications in T2DM, but the effects of antidiabetic drugs on macrovascular complications and mortality in T2DM are less clear. The results of recent trials have demonstrated clear evidence that empagliflozin and liraglutide reduce cardiovascular (CV) and all-cause mortality in T2DM, an effect that is absent in other members of antidiabetic drugs. Empagliflozin is a member of a novel class of antidiabetic drugs, the sodium-glucose co-transporter 2 (SGLT2) inhibitors. Two ongoing randomized clinical trials involving other SGLT2 inhibitors, canagliflozin and dapagliflozin, will provide additional evidence of the beneficial effects of SGLT2 inhibitors in T2DM population. The aim of this paper is to systematically present the latest evidence regarding the usage of antidiabetic drugs, and the reduction of macrovascular complications and mortality. A special emphasis is put on the novel class of antidiabetic drugs, of SGLT2 inhibitors. Key messages Macrovascular complications and mortality are best clinical trial endpoints for evaluating the efficacy of antidiabetic drugs. The first antidiabetic drug that demonstrated a reduction in mortality in the treatment of type 2 diabetes mellitus (T2DM) was empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor. SGLT2 inhibitors are novel class of antidiabetic drugs that play a promising role in the treatment of T2DM.

Emergency Medical Response Capability Analysis

DTIC Science & Technology

1982-07-01

Analgesics, non-narcotic Anesthesia aooaratus Antibiotics and anti-bacterials Basin, qash, solution Antidiabetic Agents (Oral) Blade, surgical Knife...for replace- Holder, suture needle nent therapy Inhaler, anesthesia , Yankauer (atner fask) Local anesthetics Intravenous injection sets Lubricant...Medium-Spectrum Erythromycin Kanamycin Clindamycin Narrow-Spectrum Penicillins Oxacillin Methicillin Streptomycin Gentamicin Other Amphotericin B Nystatin

Randomized study of repaglinide alone and in combination with metformin in Chinese subjects with type 2 diabetes naive to oral antidiabetes therapy.

PubMed

Wang, Weiqing; Bu, Ruifang; Su, Qing; Liu, Jianying; Ning, Guang

2011-12-01

The aim of this research is to determine efficacy and safety of repaglinide alone and in combination with metformin in Chinese subjects with type 2 diabetes naive to oral antidiabetes therapy. A 16-week, open-label, randomized, active-controlled, parallel-group trial was carried out. Subjects were randomized (1:1) to repaglinide 1 mg t.i.d. (maximum dose, 4 mg t.i.d.) or repaglinide plus metformin 1 mg/500 mg t.i.d. (maximum dose, 4 mg/500 mg t.i.d.). Eligible subjects (18 - 75 years old) had type 2 diabetes, A1C > 8.5%, BMI ≤ 35 kg/m(2), and were naive to oral antidiabetes agents. The primary outcome was A1C reduction. Secondary end points included fasting plasma glucose (FPG), 2-h postprandial glucose (PPG), and 7-point plasma glucose. Baseline characteristics (repaglinide/metformin, n = 218; repaglinide-only, n = 214) were similar between groups. Mean A1C reduction (± SD) was 4.51 ± 1.64% (combination) and 4.05 ± 1.59% (monotherapy). Estimated mean treatment difference for repaglinide/metformin versus repaglinide-only was -0.30% (95% CI -0.49 to -0.11; p < 0.01). Combination treatment demonstrated significant improvements versus monotherapy in FPG, 7-point plasma glucose, and lunchtime and dinnertime 2-h PPG (all p < 0.05). Hypoglycemia rates were 2.04 (combination) versus 1.35 (monotherapy) events/subject-year (p = 0.058). Adverse events were comparable between groups. Repaglinide plus metformin and repaglinide alone provided significant improvements in glycemic control and were well tolerated in Chinese patients naive to treatment with oral antidiabetes agents. Combination therapy with repaglinide plus metformin showed superiority to repaglinide monotherapy in this population. Limitations of this study are that subjects were newly diagnosed and had high mean baseline A1C, which may affect generalizability of results.

Ginseng saponins and the treatment of osteoporosis: mini literature review

PubMed Central

Siddiqi, Muhammad Hanif; Siddiqi, Muhammad Zubair; Ahn, Sungeun; Kang, Sera; Kim, Yeon-Ju; Sathishkumar, Natarajan; Yang, Dong-Uk; Yang, Deok-Chun

2013-01-01

The ginseng plant (Panax ginseng Meyer) has a large number of active ingredients including steroidal saponins with a dammarane skeleton as well as protopanaxadiol and protopanaxatriol, commonly known as ginsenosides, which have antioxidant, anticancer, antidiabetic, anti-adipocyte, and sexual enhancing effects. Though several discoveries have demonstrated that ginseng saponins (ginsenosides) as the most important therapeutic agent for the treatment of osteoporosis, yet the molecular mechanism of its active metabolites is unknown. In this review, we summarize the evidence supporting the therapeutic properties of ginsenosides both in vivo and in vitro, with an emphasis on the different molecular agents comprising receptor activator of nuclear factor kappa-B ligand, receptor activator of nuclear factor kappa-B, and matrix metallopeptidase-9, as well as the bone morphogenetic protein-2 and Smad signaling pathways. PMID:24198650

Effect of hypolipidemic drugs on basal and stimulated adenylate cyclase activity in tumor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bershtein, L.M.; Kovaleva, I.G.; Rozenberg, O.A.

1986-02-01

This paper studies adenylate cyclase acticvity in Ehrlich's ascites carcinoma (EAC) cells during administration of drugs with a hypolipidemic action. Seven to eight days before they were killed, male mice ingested the antidiabetic biguanide phenformin, and the phospholipid-containing preparation Essentiale in drinking water. The cAMP formed was isolated by chromatography on Silufol plates after incubation of the enzyme preparation with tritium-ATP, or was determined by the competitive binding method with protein. It is shown that despite the possible differences in the concrete mechanism of action of the hypolipidemic agents chosen for study on the cyclase system, the use of suchmore » agents, offers definite prospects for oriented modification of the hormone sensitivity of tumor cells.« less

Differential anti-diabetic effects and mechanism of action of charantin-rich extract of Taiwanese Momordica charantia between type 1 and type 2 diabetic mice.

PubMed

Wang, Hsien-Yi; Kan, Wei-Chih; Cheng, Tain-Junn; Yu, Sung-Hsun; Chang, Liang-Hao; Chuu, Jiunn-Jye

2014-07-01

Momordica charantia Linn. (Cucurbitaceae), also called bitter melon, has traditionally been used as a natural anti-diabetic agent for anti-hyperglycemic activity in several animal models and clinical trials. We investigated the differences in the anti-diabetic properties and mechanism of action of Taiwanese M. charantia (MC) between type 1 diabetic (T1D) and type 2 diabetic (T2D) mice. To clarify the beneficial effects of MC, we measured non-fasting glucose, oral glucose tolerance, and plasma insulin levels in KK/HIJ mice with high-fat diet-induced diabetes (200 mg/kg/day of charantin-rich extract of MC [CEMC]) and in ICR mice with STZ-induced diabetes. After 8 weeks, all the mice were exsanguinated, and the expression of the insulin-signaling-associated proteins in their tissue was evaluated, in coordination with the protective effects of CEMC against pancreatic β-cell toxicity (in vitro). Eight weeks of data indicated that CEMC caused a significant decline in non-fasting blood glucose, plasma glucose intolerance, and insulin resistance in the KK/HIJ mice, but not in the ICR mice. Furthermore, CEMC decreased plasma insulin and promoted the sensitivity of insulin by increasing the expression of GLUT4 in the skeletal muscle and of IRS-1 in the liver of KK/HIJ mice; however, CEMC extract had no effect on the insulin sensitivity of ICR mice. In vitro study showed that CEMC prevented pancreatic β cells from high-glucose-induced cytotoxicity after 24 h of incubation, but the protective effect was not detectable after 72 h. Collectively, the hypoglycemic effects of CEMC suggest that it has potential for increasing insulin sensitivity in patients with T2D rather than for protecting patients with T1D against β-cell dysfunction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Novel synergic antidiabetic effects of Astragalus polysaccharides combined with Crataegus flavonoids via improvement of islet function and liver metabolism.

PubMed

Cui, Kai; Zhang, Shaobo; Jiang, Xin; Xie, Weidong

2016-06-01

The present study investigated the synergic effects and potential mechanisms of action of Astragalus polysaccharides (APS) combined with Crataegus flavonoids (CF) in the treatment of type 1 diabetes. Diabetes was induced by intraperitoneal injection of 100 mg/kg streptozotocin in mice. Normal and untreated diabetic control mice were used, and CF‑treated (200 mg/kg/day), APS‑treated (200 mg/kg/day), APS + CF (AC)‑treated (200 mg/kg/day of each) and metformin‑treated (200 mg/kg/day) diabetic mice were orally administrated the appropriate therapeutic agent for 4 weeks. The results demonstrated that AC treatment significantly reduced the fasting blood glucose, food and water intake in the diabetic mice. The AC group demonstrated increased serum insulin levels and islet cell function was restored. Furthermore, the AC‑treated mice demonstrated significant increases in the protein expression levels of pancreatic and duodenal homeobox‑1 and phosphorylated adenosine 5'‑monophosphate‑activated protein kinase in the pancreatic and liver tissue samples, respectively. In addition, AC significantly increased the mRNA expression levels of neurogenin 3, v‑maf musculoaponeurotic fibrosarcoma oncogene family, protein A and insulin, and simultaneously decreased the expressions of interleukin 6, tumor necrosis factor‑α and chemokine (C‑C motif) ligand 2 in the pancreatic islet cells of diabetic mice. The anti‑inflammatory activity of APS and the islet‑restoring effect of CF may contribute to the improvement of islet function. AC exerted greater antidiabetic effects compared with APS or CF treatments alone. These results indicated that AC treatment had a synergic antidiabetic effect, which may involve improvements in islet function and liver metabolism. These effects of AC may facilitate the treatment of type 1 or 2 diabetes, as these patients frequently experience impaired islet function and disordered extrapancreatic metabolism.

Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice

PubMed Central

Allard, Joanne S.; Perez, Evelyn J; Fukui, Koji; Carpenter, Priscilla; Ingram, Donald K.; de Cabo, Rafael

2016-01-01

Long-term use of anti-diabetic agents has become commonplace as rates of obesity, metabolic syndrome and diabetes continue to escalate. Metformin, a commonly used anti-diabetic drug, has been shown to have many beneficial effects outside of its therapeutic regulation of glucose metabolism and insulin sensitivity. Studies on metformin’s effects on the central nervous system are limited and predominantly consist of in vitro studies and a few in vivo studies with short-term treatment in relatively young animals; some provide support for metformin as a neuroprotective agent while others show evidence that metformin may be deleterious to neuronal survival. In this study, we examined the effect of long-term metformin treatment on brain neurotrophins and cognition in aged male C57Bl/6 mice. Mice were fed control (C), high-fat (HF) or a high-fat diet supplemented with metformin (HFM) for 6 months. Metformin decreased body fat composition and attenuated declines in motor function induced by a HF diet. Performance in the Morris water maze test of hippocampal based memory function, showed that metformin prevented impairment of spatial reference memory associated with the HF diet. Quantitative RT-PCR on brain homogenates revealed decreased transcription of BDNF, NGF and NTF3; however protein levels were not altered. Metformin treatment also decreased expression of the antioxidant pathway regulator, Nrf2. The decrease in transcription of neurotrophic factors and Nrf2 with chronic metformin intake, cautions of the possibility that extended metformin use may alter brain biochemistry in a manner that creates a vulnerable brain environment and warrants further investigation. PMID:26698400

Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice.

PubMed

Allard, Joanne S; Perez, Evelyn J; Fukui, Koji; Carpenter, Priscilla; Ingram, Donald K; de Cabo, Rafael

2016-03-15

Long-term use of anti-diabetic agents has become commonplace as rates of obesity, metabolic syndrome and diabetes continue to escalate. Metformin, a commonly used anti-diabetic drug, has been shown to have many beneficial effects outside of its therapeutic regulation of glucose metabolism and insulin sensitivity. Studies on metformin's effects on the central nervous system are limited and predominantly consist of in vitro studies and a few in vivo studies with short-term treatment in relatively young animals; some provide support for metformin as a neuroprotective agent while others show evidence that metformin may be deleterious to neuronal survival. In this study, we examined the effect of long-term metformin treatment on brain neurotrophins and cognition in aged male C57Bl/6 mice. Mice were fed control (C), high-fat (HF) or a high-fat diet supplemented with metformin (HFM) for 6 months. Metformin decreased body fat composition and attenuated declines in motor function induced by a HF diet. Performance in the Morris water maze test of hippocampal based memory function, showed that metformin prevented impairment of spatial reference memory associated with the HF diet. Quantitative RT-PCR on brain homogenates revealed decreased transcription of BDNF, NGF and NTF3; however protein levels were not altered. Metformin treatment also decreased expression of the antioxidant pathway regulator, Nrf2. The decrease in transcription of neurotrophic factors and Nrf2 with chronic metformin intake, cautions of the possibility that extended metformin use may alter brain biochemistry in a manner that creates a vulnerable brain environment and warrants further investigation. Copyright © 2015 Elsevier B.V. All rights reserved.

Zingiber officinale and Type 2 Diabetes Mellitus: Evidence from Experimental Studies.

PubMed

Akash, Muhammad Sajid Hamid; Rehman, Kanwal; Tariq, Muhammad; Chen, Shuqing

2015-01-01

Zingiber officinale is being used as diet-based therapy because of its wide therapeutic potential in type 2 diabetes mellitus (T2DM) and against diabetic complications by directly interacting with different molecular and cellular pathways that provoke the pathogenesis of T2DM. This article explores the overall beneficial effects of Z. officinale on T2DM and its associated complications. Along with elucidating the beneficial facts of Z. officinale, this article may also aid in understanding the molecular basis of its effects in T2DM. The mechanistic rationale for antidiabetic effects of Z. officinale includes the inhibition of several transcriptional pathways, lipid peroxidation, carbohydrate-metabolizing enzymes, and HMG-CoA reductase and the activation of antioxidant enzyme capacity and low-density lipoprotein receptors. Consequently, by targeting these pathways, Z. officinale shows its antidiabetic therapeutic effects by increasing insulin sensitivity/synthesis, protecting β-cells of pancreatic islets, reducing fat accumulation, decreasing oxidative stress, and increasing glucose uptake by the tissues. In addition to these effects, Z. officinale also exhibits protective effects against several diabetes-linked complications, notably nephropathy and diabetic cataract, by acting as an antioxidant and antiglycating agent. In conclusion, this work suggests that consumption of Z. officinale can help to treat T2DM and diabetic complications; nevertheless, patient counseling also is required as a guiding force for the success of diet-based therapy in T2DM.

Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease - cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort.

PubMed

Busch, Martin; Nadal, Jennifer; Schmid, Matthias; Paul, Katharina; Titze, Stephanie; Hübner, Silvia; Köttgen, Anna; Schultheiss, Ulla T; Baid-Agrawal, Seema; Lorenzen, Johan; Schlieper, Georg; Sommerer, Claudia; Krane, Vera; Hilge, Robert; Kielstein, Jan T; Kronenberg, Florian; Wanner, Christoph; Eckardt, Kai-Uwe; Wolf, Gunter

2016-06-11

Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD. The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) between 30-60 mL/min/1.73 m(2) or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure. At baseline, DM was present in 1842 patients (35 %) and the median HbA1C was 7.0 % (25(th)-75(th) percentile: 6.8-7.9 %), equalling 53 mmol/mol (51, 63); 24.2 % of patients received dietary treatment only, 25.5 % oral antidiabetic drugs but not insulin, 8.4 % oral antidiabetic drugs with insulin, and 41.8 % insulin alone. Metformin was used by 18.8 %. Factors associated with an HbA1C level >7.0 % (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m(2), 95 % CI 1.02-1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 % CI 1.04-1.18), treatment with insulin alone (OR = 5.63, 95 % CI 4.26-7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 % CI 2.77-6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides. Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 % receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels.

Synthesis of Thymoquinone derivatives and its activity analysis: In-silico approach

NASA Astrophysics Data System (ADS)

Ulfa, Siti Mariyah; Sholikhah, Shoimatus; Utomo, Edi Priyo

2017-03-01

Thymoquinone derivatives which synthesized in this research is bromoalkylquinones with alkyl chain consist of seven carbons (C7) and ten carbons (C10). The synthesis was carried out by oxidation of 2,3-dimethylhydroquinone followed by alkylation using reflux for 1.5 hours. The alkylation products were successfully characterized as 5-(7-bromoheptyl)-2,3-dimethyl-1,4-benzoquinone (C7) and 5-(10-bromodecyl)-2,3-dimethyl-1,4-benzoquinone (C10) in 31.93 and 16.89%, respectively. These compounds were fully characterized using FT-IR, 1H-NMR and 13C-NMR. Thus, the activity of C7 and C10 was analyzed by in silico approach with molecular docking using macromolecule model extracted from Protein Data Bank (PDB). Macromolecules used in this research is mitochondrial translocator protein (TSPO) as an antioxidant receptor, glycogen phosphorylase (GPA) as antidiabetic receptor and phosphatase tensin homolog (PTEN) as an anticancer agent. The result showed that C7 and C10 has a very good activity as antioxidant and antidiabetic agents with IC50 2.03 and 1.02 ppm (TSPO) and 16.98 and 14.88 ppm (GPA) compared with Thymoquinone. While the activity of C7 and C10 against PTEN gave the IC50 23.13 and 18.31 ppm showed a good candidate for an anticancer agent.

Effects of Cocoa Antioxidants in Type 2 Diabetes Mellitus.

PubMed

Ramos, Sonia; Martín, María Angeles; Goya, Luis

2017-10-31

Type 2 Diabetes mellitus (T2D) is the most common form of diabetes and one of the most common chronic diseases. Control of hyperglycaemia by hypoglycaemic drugs is insufficient in for patients and nutritional approaches are currently being explored. Natural dietary compounds such as flavonoids, abundant in fruits and vegetables, have received broad attention because of their potential capacity to act as anti-diabetic agents. Especially cocoa flavonoids have been proved to ameliorate important hallmarks of T2D. In this review, an update of the most relevant reports published during the last decade in cell culture, animal models and human studies is presented. Most results support an anti-diabetic effect of cocoa flavonoids by enhancing insulin secretion, improving insulin sensitivity in peripheral tissues, exerting a lipid-lowering effect and preventing the oxidative and inflammatory damages associated to the disease. While it could be suggested that daily consumption of flavanols from cocoa or dark chocolate would constitute a potential preventive tool useful for the nutritional management of T2D, this recommendation should be cautious since most of commercially available soluble cocoa products or chocolates contain low amount of flavanols and are rich in sugar and calories that may aggravate glycaemic control in T2D patients.

Effects of Cocoa Antioxidants in Type 2 Diabetes Mellitus

PubMed Central

Martín, María Angeles; Goya, Luis

2017-01-01

Type 2 Diabetes mellitus (T2D) is the most common form of diabetes and one of the most common chronic diseases. Control of hyperglycaemia by hypoglycaemic drugs is insufficient in for patients and nutritional approaches are currently being explored. Natural dietary compounds such as flavonoids, abundant in fruits and vegetables, have received broad attention because of their potential capacity to act as anti-diabetic agents. Especially cocoa flavonoids have been proved to ameliorate important hallmarks of T2D. In this review, an update of the most relevant reports published during the last decade in cell culture, animal models and human studies is presented. Most results support an anti-diabetic effect of cocoa flavonoids by enhancing insulin secretion, improving insulin sensitivity in peripheral tissues, exerting a lipid-lowering effect and preventing the oxidative and inflammatory damages associated to the disease. While it could be suggested that daily consumption of flavanols from cocoa or dark chocolate would constitute a potential preventive tool useful for the nutritional management of T2D, this recommendation should be cautious since most of commercially available soluble cocoa products or chocolates contain low amount of flavanols and are rich in sugar and calories that may aggravate glycaemic control in T2D patients. PMID:29088075

The enhancement of oxidative DNA damage by anti-diabetic metformin, buformin, and phenformin, via nitrogen-centered radicals.

PubMed

Ohnishi, Shiho; Mizutani, Hideki; Kawanishi, Shosuke

2016-08-01

Metformin (N,N-dimethylbiguanide), buformin (1-butylbiguanide), and phenformin (1-phenethylbiguanide) are anti-diabetic biguanide drugs, expected to having anti-cancer effect. The mechanism of anti-cancer effect by these drugs is not completely understood. In this study, we demonstrated that these drugs dramatically enhanced oxidative DNA damage under oxidative condition. Metformin, buformin, and phenformin enhanced generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in isolated DNA reacted with hydrogen peroxide (H2O2) and Cu(II), although these drugs did not form 8-oxodG in the absence of H2O2 or Cu(II). An electron paramagnetic resonance (EPR) study, utilizing alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone and 3,3,5,5-tetramethyl-1-pyrroline-N-oxide as spin trapping agents, showed that nitrogen-centered radicals were generated from biguanides in the presence of Cu(II) and H2O2, and that these radicals were decreased by the addition of DNA. These results suggest that biguanides enhance Cu(II)/H2O2-mediated 8-oxodG generation via nitrogen-centered radical formation. The enhancing effect on oxidative DNA damage may play a role on anti-cancer activity.

Effect of salinity medium on antioxidant and antidiabetic activity marine endophytic fungus of asperegillus elegans ptf 9

NASA Astrophysics Data System (ADS)

Mulyani, Hani; Artanti, Nina; Fitria, Irni; Filailla, Euis; Kandace, Yoice Sri; Udin, Linar Zalinar

2017-11-01

Our previous studies on screening of antioxidant activities from various endophytic fungi isolated from marine bioata showed that A. elegans PTF9 isolated from sea weed is one of the fungus that has good antioxidant activity. In current study we reported the effect of medium salinity (0, 3 and 10% salt in PDB medium) on antioxidant and antidiabetes activity of mycelium and filtrate ethyl acetate extracts of A. elegans Ptf 9. The antioxidant assay was conducted using DPPH free radical scavenging activity method. The antidiabetes assay was conducted using a-glucosidase inhibitory activity method. The results showed that the best antioxidant activity was obtained from filtrate extract of fungus cultures with 0% salt (IC50=1.56 ppm), whereas the best antidiabetes activity was obtained from filtrate extract of fungus culture with 10% salt (IC50= 3.64 ppm). Addition of salt reduced the antioxidant activity, but not the antidiabetes activity. The results suggest that A. elegans PTF9 showed potential for further studies on isolation of antioxidant and antidiabetes lead compounds that could be use for further development of new drugs.

[Rosiglitazone (BRL-49653)].

PubMed

Kameda, N; Okuya, S; Oka, Y

2000-02-01

Rosiglitazone, a thiazolidinedion antidiabetic agent, improves insulin resistance in patients with type 2 diabetes mellitus. Rosiglitazone binds to PPAR-gamma with high affinity and the in vivo antidiabetic potency of rosiglitazone is correlated with its high biding affinity. In animal models of insulin resistence, rosiglitazone decreased plasma glucose, triglyceride and insulin levels and also prevented diabetic nephropathy and pancreatic islet cell degeneration. In clinical trials in patients with type 2 diabetes mellitus, rosiglitazone, 2 to 12 mg/day (as a single daily dose or 2 divided daily doses), improved glycemic control as demonstrated, by decreases in fasting plasma glucose and HbA1C levels. Rosiglitazone did not appear to increase the risk of hypoglycemia and there was no evidence of hepatotoxicity in pre-clinical trials.

Acute and chronic animal models for the evaluation of anti-diabetic agents

PubMed Central

2012-01-01

Diabetes mellitus is a potentially morbid condition with high prevalence worldwide thus being a major medical concern. Experimental induction of diabetes mellitus in animal models is essential for the advancement of our knowledge and understanding of the various aspects of its pathogenesis and ultimately finding new therapies and cure. Experimental diabetes mellitus is generally induced in laboratory animals by several methods that include: chemical, surgical and genetic (immunological) manipulations. Most of the experiments in diabetes are carried out in rodents, although some studies are still performed in larger animals. The present review highlights the various methods of inducing diabetes in experimental animals in order to test the newer drugs for their anti-diabetic potential. PMID:22257465

On the potential of acarbose to reduce cardiovascular disease

PubMed Central

2014-01-01

In the emerging landscape of cardiovascular (CV) outcome trials evaluating the effects of blood glucose lowering drugs in individuals with type 2 diabetes, it is becoming increasingly apparent that since the promising signals coming from the United Kingdom Prospective Diabetes Study (UKPDS) no unequivocal benefits have been established for any single therapy thus far. There is an unmet need for introducing an effective pharmacological agent which could target both correlates of glycaemic regulation and CV risk factors, to ameliorate the enormous burden of fatal and non-fatal CV events in diabetic patients. Acarbose, like other alpha-glucosidase inhibitors (AGIs), has been proven to be an effective antidiabetic treatment for decades, but the overall significant impact of this class of drugs on modulating CV risk has only recently been appreciated. Accumulating evidence has shown that apart from its multiple effects on primarily postprandial glucose dysmetabolism, a key component of mechanisms linked to increased incidence of CV events, acarbose therapy also associates with a favorable impact on an array of surrogate markers of CV disease. Data stemming from in vitro testing of human cell lines as well as from preliminary trials in diabetic populations, like the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial, have highlighted – though not undisputed – the potential beneficial effects of the drug on CV morbidity. Large scale trials, like the ongoing Acarbose Cardiovascular Evaluation (ACE) trial, aim at conclusively establishing such a positive effect in patients with coronary heart disease and impaired glucose tolerance. In view of its usually acceptable level of side effects that are, if they occur, mostly limited to transient gastrointestinal symptoms, acarbose could well be a strong future player in CV disease secondary prevention. Current discouraging results from many trials of antidiabetic medications to significantly lower CV event rates in diabetic patients, should only draw further attention on alternative glucose lowering agents, among which acarbose is indeed promising. PMID:24742256

On the potential of acarbose to reduce cardiovascular disease.

PubMed

Standl, Eberhard; Theodorakis, Michael J; Erbach, Michael; Schnell, Oliver; Tuomilehto, Jaakko

2014-04-16

In the emerging landscape of cardiovascular (CV) outcome trials evaluating the effects of blood glucose lowering drugs in individuals with type 2 diabetes, it is becoming increasingly apparent that since the promising signals coming from the United Kingdom Prospective Diabetes Study (UKPDS) no unequivocal benefits have been established for any single therapy thus far. There is an unmet need for introducing an effective pharmacological agent which could target both correlates of glycaemic regulation and CV risk factors, to ameliorate the enormous burden of fatal and non-fatal CV events in diabetic patients. Acarbose, like other alpha-glucosidase inhibitors (AGIs), has been proven to be an effective antidiabetic treatment for decades, but the overall significant impact of this class of drugs on modulating CV risk has only recently been appreciated. Accumulating evidence has shown that apart from its multiple effects on primarily postprandial glucose dysmetabolism, a key component of mechanisms linked to increased incidence of CV events, acarbose therapy also associates with a favorable impact on an array of surrogate markers of CV disease. Data stemming from in vitro testing of human cell lines as well as from preliminary trials in diabetic populations, like the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial, have highlighted - though not undisputed - the potential beneficial effects of the drug on CV morbidity. Large scale trials, like the ongoing Acarbose Cardiovascular Evaluation (ACE) trial, aim at conclusively establishing such a positive effect in patients with coronary heart disease and impaired glucose tolerance. In view of its usually acceptable level of side effects that are, if they occur, mostly limited to transient gastrointestinal symptoms, acarbose could well be a strong future player in CV disease secondary prevention. Current discouraging results from many trials of antidiabetic medications to significantly lower CV event rates in diabetic patients, should only draw further attention on alternative glucose lowering agents, among which acarbose is indeed promising.

Natural Prenylchalconaringenins and Prenylnaringenins as Antidiabetic Agents: α-Glucosidase and α-Amylase Inhibition and in Vivo Antihyperglycemic and Antihyperlipidemic Effects.

PubMed

Sun, Hua; Wang, Dong; Song, Xiaotong; Zhang, Yazhou; Ding, Weina; Peng, Xiaolin; Zhang, Xiaoting; Li, Yashan; Ma, Ying; Wang, Runling; Yu, Peng

2017-03-01

Inhibition of α-glucosidase and α-amylase decreases postprandial blood glucose levels and delays glucose absorption, making it a treatment strategy for type 2 diabetes. This study examined in vivo and in vitro antidiabetic activities of natural prenylchalconaringenins 1 and 2 and prenylnaringenins 3 and 4, found in hops and beer. 3'-Geranylchalconaringenin (2) competitively and irreversibly inhibited α-glucosidase (IC 50 = 1.08 μM) with activity 50-fold higher than that of acarbose (IC 50 = 51.30 μM) and showed moderate inhibitory activity against α-amylase (IC 50 = 20.46 μM). Docking analysis substantiated these findings. In addition, compound 2 suppressed the increase in postprandial blood glucose levels and serum levels of total cholesterol and triglycerides in streptozotocin-induced diabetic mice. Taken together, these results suggest that 2 has dual inhibitory activity against α-glucosidase and α-amylase and alleviates diabetic hyperglycemia and hyperlipidemia, making it a potential functional food ingredient and drug candidate for management of type 2 diabetes.

Orally Administered Baker's Yeast β-Glucan Promotes Glucose and Lipid Homeostasis in the Livers of Obesity and Diabetes Model Mice.

PubMed

Cao, Yan; Sun, Ying; Zou, Siwei; Li, Mengxia; Xu, Xiaojuan

2017-11-08

Baker's yeast glucan (BYG) has been reported to be an anti-diabetic agent. In the work described herein, further study on the effect of orally administered BYG on glucose and lipid homeostasis in the livers of ob/ob mice was performed. It was found that BYG decreased the blood glucose and the hepatic glucose and lipid disorders. Western blotting analysis revealed that BYG up-regulated p-AKT and p-AMPK, and down-regulated p-Acc in the liver. Furthermore, RNA-Seq analysis indicated that BYG down-regulated genes responsible for gluconeogenesis (G6pase and Got1), fatty acid biosynthesis (Acly, Acc, Fas, etc.), glycerolipid synthesis (Gpam and Lipin1/2), and cholesterol synthesis (Hmgcr, Fdps, etc.). Additionally, BYG decreased glucose transporters SGLT1 and GLUT2, fat emulsification, and adipogenic genes/proteins in the intestine to decrease glucose and lipid absorption. All these findings demonstrated that BYG is beneficial for regulating glucose and lipid homeostasis in diabetic mice, and thus has potential applications in anti-diabetic foods or drugs.

[Effectiveness of phytotherapy in supportive treatment of type 2 diabetes mellitus III. Momordica (Momordica charantia)].

PubMed

Rudá-Kučerová, Jana; Kotolová, Hana; Koupý, David

2015-09-01

Momordica charantia is a thermophilic voluble plant from the tropical and subtropical regions of Asia, Africa and the Caribbean. In central Europe, momordica requires greenhouse plantations. Mature fruits resemble a cucumber or a pumpkin and can be used as other similar vegetables. Crude fruits are very bitter and refreshing. For centuries the plant has been known in Chinese traditional medicine for its antidiabetic effects as well as for the treatment of cancer or infections caused by worms, viruses and malaria. Antidiabetic effects are attributed namely to cucurbitane type triterpenoids, charantin, p-insulin and 9cis-11trans-13trans-conjugated linolenic acid. These substances in momordica preparations show antidiabetic effectiveness in clinical studies by increasing insulin secretion and deceasing insulin resistance or glucose absorption from the gut. Beside this main effect the extract possesses certain neuroprotective and antioxidant effects (especially p9cis-11trans-13trans-conjugated linolenic acid) and contributes to normalize blood lipid and adipokine levels which results in the normalization of metabolic syndrome. Antidiabetic effectiveness of momordica was compared to active treatment with several oral antidiabetic drugs and proved comparable effects. However, the number of studies is limited and their methodological approach variable. Therefore, the evidence is so far inconclusive.

Antidiabetic activity of mefloquine via GLP-1 receptor modulation against STZ-NA-induced diabetes in albino wistar rats.

PubMed

Yadav, Rajnish Kumar; Rawat, Jitendra K; Gautam, Swetlana; Singh, Manjari; Kumar, Manish; Ansari, Mohd Nazam; Roy, Subhadeep; Saeedan, Abdulaziz S; Kaithwas, Gaurav

2018-05-01

Mefloquine was retrieved as a glucagon -like peptide-1 receptor agonist and, therefore, evaluated for its antidiabetic potential against non-insulin-dependent diabetes mellitus (NIDDM) in experimental animals. NIDDM was induced by single intraperitoneal injection of streptozotocin and nicotinamide (60 + 110 mg/kg) in albino wistar rats. The experimental animals were scrutinised for electrocardiographic (ECG) and heart rate variability (HRV) factors to study the autonomic dysfunction along with blood glucose, serum insulin, and liver glycogen levels for glycemic control. Simultaneously, antioxidant markers (TBARs, protein carbonyl, GSH, SOD, catalase) and inflammatory markers (COX, LOX, NO) were scrutinized as well. Oral administration of mefloquine normalised the heart rate with favourable regulation of time and frequency domain HRV parameters. Mefloquine restored the blood glucose, serum insulin, and liver glycogen levels favourably in diabetic rats. Treatment with mefloquine curtailed the antioxidant markers with favourable regulation of inflammatory signals. Mefloquine was also found to be less hepatotoxic in contrast to the standard metformin, providing an integrated advantage as an antidiabetic agent.

The antidiabetic action of camel milk in experimental type 2 diabetes mellitus: an overview on the changes in incretin hormones, insulin resistance, and inflammatory cytokines.

PubMed

Korish, A A

2014-06-01

Folk medicine stories accredited the aptitude of camel milk (CMK) as a hypoglycemic agent and recent studies have confirmed this in the diabetic patients and experimental animals. However, the mechanism(s) by which CMK influences glucose homeostasis is yet unclear. The current study investigated the changes in the glucose homeostatic parameters, the incretin hormones, and the inflammatory cytokines in the CMK-treated diabetic animals. A model of type 2 diabetes mellitus was induced in rats by intraperitoneal injection of streptozotocin 40 mg/kg/day for 4 repeated doses. Camel milk treatment was administered for 8 weeks. The changes in glucagon like peptide-1 (GLP-1), glucose dependent insulinotropic peptide (GIP), glucose tolerance, fasting and glucose-stimulated insulin secretion, insulin resistance (IR), TNF-α, TGF-β1, lipid profile, atherogenic index (AI), and body weight were investigated. The untreated diabetic animals showed hyperglycemia, increased HOMA-IR, hyperlipidemia, elevated AI, high serum incretins [GLP-1 and GIP], TNF-α, and TGF-β1 levels and weight loss as compared with the control group. Camel milk treatment to the diabetic animals resulted in significant lowered fasting glucose level, hypolipidemia, decreased HOMA-IR, recovery of insulin secretion, weight gain, and no mortality during the study. Additionally, CMK inhibits the diabetes-induced elevation in incretin hormones, TNF-α and TGF-β1 levels. The increase in glucose-stimulated insulin secretion, decreased HOMA-IR, modulation of the secretion and/or the action of incretins, and the anti-inflammatory effect are anticipated mechanisms to the antidiabetic effect of CMK and suggest it as a valuable adjuvant antidiabetic therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Redox properties of ginger extracts: Perspectives of use of Zingiber officinale Rosc. as antidiabetic agent

PubMed Central

Cupáková, Máriá; Ťažký, Anton; Mičová, Júlia; Kolek, Emil; Košt'álová, Daniela

2013-01-01

In traditional medicine, several medicinal plants or their extracts have been used to treat diabetes. Zingiber officinale Roscoe, known commonly as ginger, is consumed worldwide in cookeries as a spice and flavouring agent. It has been used as the spice and medicine for thousands of years. The present study was undertaken to investigate the potential protective effect of Zingiber officinale Rosc. in a model of oxidative damage to pancreatic β cells. The free radical scavenging activities and composition of the isolated n-hexane and ethanolic extracts were confronted with their protective, antioxidant and cytotoxic effects in INS-1E β cells. Unlike the n-hexane extract (exerting, paradoxically, stronger antiradical capacity), both low cytotoxicity and remarkable protective effects on β cell viability, followed by lowering oxidative stress markers were found for the ethanolic extract Zingiber officinale Rosc. The present study is the first pilot study to assess the protective potential of Zingiber officinale Rosc. in a model of cytotoxic conditions imposed by diabetes in β cells. PMID:24170976

Redox properties of ginger extracts: Perspectives of use of Zingiber officinale Rosc. as antidiabetic agent.

PubMed

Račková, Lucia; Cupáková, Máriá; Tažký, Anton; Mičová, Júlia; Kolek, Emil; Košt'álová, Daniela

2013-03-01

In traditional medicine, several medicinal plants or their extracts have been used to treat diabetes. Zingiber officinale Roscoe, known commonly as ginger, is consumed worldwide in cookeries as a spice and flavouring agent. It has been used as the spice and medicine for thousands of years. The present study was undertaken to investigate the potential protective effect of Zingiber officinale Rosc. in a model of oxidative damage to pancreatic β cells. The free radical scavenging activities and composition of the isolated n-hexane and ethanolic extracts were confronted with their protective, antioxidant and cytotoxic effects in INS-1E β cells. Unlike the n-hexane extract (exerting, paradoxically, stronger antiradical capacity), both low cytotoxicity and remarkable protective effects on β cell viability, followed by lowering oxidative stress markers were found for the ethanolic extract Zingiber officinale Rosc. The present study is the first pilot study to assess the protective potential of Zingiber officinale Rosc. in a model of cytotoxic conditions imposed by diabetes in β cells.

Pathophysiology and Medical Treatment of Carotid Artery Stenosis

PubMed Central

Prasad, Kailash

2015-01-01

Stroke is the third leading cause of mortality. Approximately 80 to 85% strokes are ischemic due to carotid artery stenosis (CAS). The prevalence of significant CAS is 7% in women and 9% in men. Severe asymptomatic CAS varies from 0 to 3.1%. Prevalence of symptomatic CAS is high in patients with peripheral arterial disease. CAS is due to atherosclerosis, the major risk factors for which include dyslipidemia, hypertension, diabetes, obesity, cigarette smoking, advanced glycation end products (AGEs) and its receptors (RAGE, soluble RAGE [sRAGE]), lack of exercise and C-reactive protein (CRP). This article discusses the basic mechanism of atherosclerosis and the mechanisms by which these risk factors induce atherosclerosis. The role of AGEs and its receptors in the development and progression of CAS has been discussed in detail. Lifestyle changes and medical treatment of CAS such as lifestyle changes, lipid-lowering agents, antihypertensive agents, antidiabetic drugs, anti-AGE therapy, measures to elevate soluble receptors of AGE (sRAGE, esRAGE). CRP-lowering agents have been discussed in detail. The drugs especially lipid-lowering agents, and antihypertensive and antidiabetic drugs suppress, regress, and slow the progression of CAS. The possible role of lowering the levels of AGEs and raising the levels of sRAGE in the treatment of CAS has been proposed. Lifestyle changes besides medical treatment have been stressed. Lifestyle changes and medical treatment not only would slow the progression of CAS but would also regress the CAS. PMID:26417183

Antiobesity effects and improvement of insulin sensitivity by 1-deoxynojirimycin in animal models.

PubMed

Kong, Won-Ho; Oh, Seung-Hoon; Ahn, You-Ran; Kim, Kwang-Won; Kim, Jin-Hoon; Seo, Soo-Won

2008-04-23

The alpha-glucosidase inhibitor 1-deoxynojirimycin (DNJ) is one of the simplest naturally occurring carbohydrate mimics, with promising biological activity in vivo. Although there is considerable interest in the pharmacological effects of DNJ, the antidiabetic effects of DNJ in type 2 diabetes mellitus have received little attention. In this work, DNJ was isolated from the silkworm (Bombyx mori), and its antidiabetic effects were evaluated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an established animal model of human type 2 diabetes mellitus, and in control Long-Evans Tokushima Otsuka (LETO) rats. DNJ treatment showed significant antidiabetic effects in OLETF rats, with significant improvements in fasting blood glucose levels and glucose tolerance and, especially, increased insulin sensitivity. Furthermore, there was significant loss of body weight in both groups. DNJ also showed significant antihyperglycemic effects in streptozotocin- and high-fat-diet-induced hyperglycemic rats. Its efficacy and dose profiles were better than those of acarbose, a typical alpha-glucosidase inhibitor in clinical use. Furthermore, a substantial fraction of DNJ was absorbed into the bloodstream within a few minutes of oral administration. DNJ was also detected in the urine. These findings suggest that its postprandial hypoglycemic effect in the gastrointestinal tract is a possible but insufficient mechanism of action underlying the antidiabetic effects of DNJ. Its antiobesity effect and improvement of insulin sensitivity are other possible antidiabetic effects of DNJ.

The complexities of obesity, diabetes, and the development and progression of pancreatic cancer

PubMed Central

Bao, Bin; Wang, Zhiwei; Li, Yiwei; Kong, Dejuan; Ali, Shadan; Banerjee, Sanjeev; Ahmad, Aamir; Sarkar, Fazlul H.

2011-01-01

Pancreatic cancer (PC) is one of the most lethal malignant diseases with the worst prognosis. It is ranked as the fourth leading cause of cancer-related deaths in the United States. Many risk factors have been associated with PC. Interestingly, large numbers of epidemiological studies suggest that obesity and diabetes, especially type-2 diabetes, are positively associated with increased risk of PC. Similarly, these chronic diseases (obesity, diabetes and cancer) are also a major public health concern. In the U.S. population, 50 percent are overweight, 30 percent are medically obese and 10 percent have diabetes mellitus (DM). Therefore, obesity and DM have been considered as potential risk factors for cancers; however, the focus of this article is restricted to PC. Although the mechanisms responsible for the development of these chronic diseases leading to the development of PC are not fully understood, the biological importance of the activation of insulin, insulin like growth factor-1 (IGF-1) and its receptor (IGF-1R) signaling pathways in insulin resistance mechanism and subsequent induction of compensatory hyperinsulinemia has been proposed. Therefore, targeting insulin/IGF-1 signaling with anti-diabetic drugs for lowering blood insulin levels and reversal of insulin-resistance could be useful strategy for the prevention and/or treatment of PC. A large number of studies have demonstrated that the administration of anti-diabetic drugs such as metformin and thiazolidinediones (TZD) class of PPAR-γ agonists decreases the risk of cancers, suggesting that these agents might be useful anti-tumor agents for the treatment of PC. In this review article, we will discuss the potential roles of metformin and TZD anti-diabetic drugs as anti-tumor agents in the context of PC, and will further discuss the complexities and the possible roles of microRNAs (miRNAs) in the pathogenesis of obesity, diabetes and PC. PMID:21129444

Herbal therapy: A review of emerging pharmacological tools in the management of diabetes mellitus in Africa

PubMed Central

Kibiti, Cromwell Mwiti; Afolayan, Anthony Jide

2015-01-01

Background: Diabetes mellitus is a chronic physiological glucose metabolic disorder. It has affected millions of people all over the world thereby having a significant impact on quality of life. The management of diabetes includes both nonpharmacological and conventional interventions. Drawbacks in conventional therapy have led to seeking alternative therapy in herbal medicine. Therefore, the need to review, elucidate and classify their mode of action in therapy for diabetes disease arises. Materials and Methods: Comprehensive literature reports were used to review all conventional agents and herbal therapy used in the management of diabetes. An online database search was conducted for medicinal plants of African origin that have been investigated for their antidiabetic therapeutic potentials. Results: The results showed that of the documented sixty five plants used, fourteen inhibit intestinal absorption of glucose, three exhibit insulin-mimetic properties, seventeen stimulate insulin secretion from pancreatic beta cells, twelve enhance peripheral glucose uptake, one promotes regeneration of beta-cell of islets of Langerhans, thirteen ameliorate oxidative stress and twenty induces hypoglycemic effect (mode of action is still obscure). Thirteen of these plants have a duplicate mode of actions while one of them has three modes of actions. These agents have a similar mechanism of action as the conventional drugs. Conclusion: In conclusion, antidiabetic activities of these plants are well established; however, the molecular modulation remains unknown. It is envisaged that the use of herbal therapy will promote good health and improve the status of diabetic patients. PMID:26664014

Optimising the medical management of hyperglycaemia in type 2 diabetes in the Middle East: pivotal role of metformin

PubMed Central

Al-Maatouq, M; Al-Arouj, M; Assaad, S H; Assaad, S N; Azar, S T; Hassoun, A A K; Jarrah, N; Zatari, S; Alberti, K G M M

2009-01-01

Aims: Increases in the prevalence of type 2 diabetes will likely be greater in the Middle East and other developing countries than in most other regions during the coming two decades, placing a heavy burden on regional healthcare resources. Methodology: Medline search, examination of data from major epidemiological studies in the Middle Eastern countries. Results: The aetiology and pathophysiology of diabetes appears comparable in Middle Eastern and other populations. Lifestyle intervention is key to the management of diabetes in all type 2 diabetes patients, who should be encouraged strongly to diet and exercise. The options for pharmacologic therapy in the management of diabetes have increased recently, particularly the number of potential antidiabetic combinations. Metformin appears to be used less frequently to initiate antidiabetic therapy in the Middle East than in other countries. Available clinical evidence, supported by current guidelines, strongly favours the initiation of antidiabetic therapy with metformin in Middle Eastern type 2 diabetes patients, where no contraindications exist. This is due to its equivalent or greater efficacy relative to other oral antidiabetic treatments, its proven tolerability and safety profiles, its weight neutrality, the lack of clinically significant hypoglycaemia, the demonstration of cardiovascular protection for metformin relative to diet in the UK Prospective Diabetes Study and in observational studies, and its low cost. Additional treatments should be added to metformin and lifestyle intervention as diabetes progresses, until patients are receiving an intensive insulin regimen with or without additional oral agents. Conclusions: The current evidence base strongly favours the initiation of antidiabetic therapy with metformin, where no contraindications exist. However, metformin may be under-prescribed in the Middle East. PMID:20089006

Peroxisome Proliferator-Activated Receptor γ (PPARγ) and Ligand Choreography: Newcomers Take the Stage.

PubMed

Garcia-Vallvé, Santiago; Guasch, Laura; Tomas-Hernández, Sarah; del Bas, Josep Maria; Ollendorff, Vincent; Arola, Lluís; Pujadas, Gerard; Mulero, Miquel

2015-07-23

Thiazolidinediones (TZDs), such as rosiglitazone and pioglitazone, are peroxisome proliferator-activated receptor γ (PPARγ) full agonists that have been widely used in the treatment of type 2 diabetes mellitus. Despite the demonstrated beneficial effect of reducing glucose levels in the plasma, TZDs also induce several adverse effects. Consequently, the search for new compounds with potent antidiabetic effects but fewer undesired effects is an active field of research. Interestingly, the novel proposed mechanisms for the antidiabetic activity of PPARγ agonists, consisting of PPARγ Ser273 phosphorylation inhibition, ligand and receptor mutual dynamics, and the presence of an alternate binding site, have recently changed the view regarding the optimal characteristics for the screening of novel PPARγ ligands. Furthermore, transcriptional genomics could bring essential information about the genome-wide effects of PPARγ ligands. Consequently, facing the new mechanistic scenario proposed for these compounds is essential for resolving the paradoxes among their agonistic function, antidiabetic activities, and side effects and should allow the rational development of better and safer PPARγ-mediated antidiabetic drugs.

Antidiabetic, antioxidant and anti inflammatory properties of water and n-butanol soluble extracts from Saharian Anvillea radiata in high-fat-diet fed mice.

PubMed

Kandouli, Chouaib; Cassien, Mathieu; Mercier, Anne; Delehedde, Caroline; Ricquebourg, Emilie; Stocker, Pierre; Mekaouche, Mourad; Leulmi, Zineb; Mechakra, Aicha; Thétiot-Laurent, Sophie; Culcasi, Marcel; Pietri, Sylvia

2017-07-31

According to Saharian traditional medicine, Anvillea radiata Coss. & Dur. (Asteraceae) has been valued for treating a variety of ailments such as gastro-intestinal, liver and pulmonary diseases, and has gained awareness for its beneficial effect on postprandial hyperglycemia. However, to best of our knowledge, no detailed study of the antidiabetic curative effects of this plant has been conducted yet. To determine the hypoglycemic and antidiabetic effect of dietary supplementation with Anvillea radiata extracts on high-fat-diet (HFD)-induced obesity and insulin resistance in C57BL/6J mice in relation with antioxidant, anti-inflammatory, pancreatic beta-cells and skeletal muscle protection, and digestive enzyme inhibiting properties. Six extracts (water soluble and organic) from aerial parts of the plant were analyzed phytochemically (total phenolic and flavonoid content) and screened for in vitro superoxide (by chemiluminescence) and hydroxyl radical (by electron paramagnetic resonance spin-trapping) scavenging, antioxidant (DPPH, TRAP and ORAC assays), xanthine oxidase, metal chelating, α-amylase and α-glucosidase inhibitory property, and protective effects on copper-induced lipoprotein oxidation. Then selected hydroalcoholic and aqueous extracts were assessed for toxicity in normal human lung fibroblasts and A549 cancer cells using FMCA and MTT assays. Two water-soluble extracts having the best overall properties were assessed for their (i) protective effect at 1-15µg/mL on metabolic activity of rat insulinoma-derived INS-1 cells exposed to hyperglycemic medium, and (ii) acute hypoglycemic effect on 16-weeks HFD-induced diabetic mice. Then diabetic mice were administered HFD supplemented by extracts (up to 150mg/kg/day) for 12 additional weeks using standard diet as control and the antidiabetic drug, metformin (150mg/kg), as positive control. Then the antidiabetic, anti-inflammatory and antioxidant activity of extracts were determined. Of the highly efficient polyphenolics-enriched hydroalcoholic and ethyl acetate extracts, the lyophilized aqueous (AQL) and butanol extracts were not toxic in cells (≤ 400µg/mL) or when given orally in normal mice (≤ 2000mg/kg), exerted a dose-dependent hypoglycemic action in diabetic mice, which was maximal at the dose of 150mg/kg. Upon administering this dose for 12 weeks, both extracts significantly ameliorated body weight control capacity, recovery of plasma glucose and insulin level, reduced oxidative stress in blood, myocardial and skeletal muscles, and improved hyperlipidemic and inflammatory status. Moreover, diabetes-related complications were optimally ameliorated by oral therapy based on halved doses (75mg/kg) of a mixture of AQL and metformin. Current investigation supports the traditional medicinal usage of Anvillea radiata and suggests that both readily accessible and low-cost bio-extracts have the potency to develop an antihyperglycemic, antihyperlipidemic and protective agent against beta-cells and muscle dysfunction at doses compatible with the common practices of indigenous people for the management of metabolic disorders. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Cost-effectiveness of exenatide twice daily vs insulin glargine as add-on therapy to oral antidiabetic agents in patients with type 2 diabetes in China.

PubMed

Gu, Shuyan; Wang, Xiaoyong; Qiao, Qing; Gao, Weiguo; Wang, Jian; Dong, Hengjin

2017-12-01

To estimate the long-term cost-effectiveness of exenatide twice daily vs insulin glargine once daily as add-on therapy to oral antidiabetic agents (OADs) for Chinese patients with type 2 diabetes (T2DM). The Cardiff Diabetes Model was used to simulate disease progression and estimate the long-term effects of exenatide twice daily vs insulin glargine once daily. Patient profiles and treatment effects required for the model were obtained from literature reviews (English and Chinese databases) and from a meta-analysis of 8 randomized controlled trials comparing exenatide twice daily with insulin glargine once daily add-on to OADs for T2DM in China. Medical expenditure data were collected from 639 patients with T2DM (aged ≥18 years) with and without complications incurred between January 1, 2014 and December 31, 2015 from claims databases in Shandong, China. Costs (2014 Chinese Yuan [¥]) and benefits were estimated, from the payers' perspective, over 40 years at a discount rate of 3%. A series of sensitivity analyses were performed. Patients on exenatide twice daily + OAD had a lower predicted incidence of most cardiovascular and hypoglycaemic events and lower total costs compared with those on insulin glargine once daily + OAD. A greater number of quality-adjusted life years (QALYs; 1.94) at a cost saving of ¥117 706 gained was associated with exenatide twice daily vs insulin glargine once daily. (i.e. cost saving of ¥60 764/QALY) per patient. In Chinese patients with T2DM inadequately controlled by OADs, exenatide twice daily is a cost-effective add-on therapy alternative to insulin glargine once daily, and may address the problem of an excess of medical needs resulting from weight gain and hypoglycaemia in T2DM treatment. © 2017 John Wiley & Sons Ltd.

Evaluation of Antidiabetic and Antihyperlipidemic Effects of Hydroalcoholic Extract of Leaves of Ocimum tenuiflorum (Lamiaceae) and Prediction of Biological Activity of its Phytoconstituents

PubMed Central

Parasuraman, Subramani; Balamurugan, Subramani; Christapher, Parayil Varghese; Petchi, Rajendran Ramesh; Yeng, Wong Yeng; Sujithra, Jeyabalan; Vijaya, Chockalingam

2015-01-01

Objective: The aim was to evaluate the anti-diabetic and anti-hyperlipidemic effects of hydroalcoholic extract of leaves of Ocimum tenuiflorum (Lamiaceae) and prediction of biological activities of its phytoconstituents using in vivo anti-diabetic model and in silico analysis respectively. Materials and Methods: The leaves of O. tenuiflorum were extracted with 60% ethanol, and the extract was used for further pharmacological screening. The acute toxicity of the extract was evaluated as per the guidelines set by the Organization for Economic Co-operation and Development, revised draft guidelines 423. The oral anti-diabetic activity of the hydroalcoholic extract of O. tenuiflorum (125, 250 and 500 mg/kg) was studied against streptozotocin (STZ) (50 mg/kg; i.p.) + nicotinamide (120 mg/kg; i.p.) induced diabetes mellitus. The animals were treated with the investigational plant extract and standard drug (glibenclamide) for 21 consecutive days and the effect of hydroalcoholic extract of O. tenuiflorum on blood glucose levels was measured at regular intervals. At the end of the study, blood samples were collected from all the animals for biochemical estimation, then the animals were sacrificed and the liver and kidney were collected for organ weight analysis. Prediction for pharmacological and toxicological properties of phytoconstituents of O. tenuiflorum was carried out using online web tools such as online pass prediction and lazar toxicity prediction. Results: The hydroalcoholic extract of O. tenuiflorum showed significant anti-diabetic and anti-hyperlipidemic activity at 250 and 500 mg/kg, and this effect was comparable with that of glibenclamide. Predicted biological activities of phytoconstituents of O. tenuiflorum showed presence of various pharmacological actions, which includes anti-diabetic and anti-hyperlipidemic activities. Prediction of toxicological properties of phytoconstituents of O. tenuiflorum did not show any major toxic effects. Conclusion: The hydroalcoholic extract of O. tenuiflorum showed significant anti-diabetic and anti-hyperlipidemic activity against STZ + nicotinamide induced diabetes mellitus in rats. Further studies are required to confirm the anti-diabetic and anti-hyperlipidemic activities of individual phytoconstituents of O. tenuiflorum. PMID:25829789

The novel gluconeogenesis inhibitor FR225654 that originates from Phoma sp. no. 00144. I. Taxonomy, fermentation, isolation and physico-chemical properties.

PubMed

Ohtsu, Yoshihiro; Sasamura, Hiromi; Tanaka, Miho; Tsurumi, Yasuhisa; Yoshimura, Seiji; Takase, Shigehiro; Shibata, Toshihiro; Hino, Motohiro; Nakajima, Hidenori

2005-07-01

FR225654, a novel gluconeogenesis inhibitor, was isolated from the culture broth of Phoma sp. No. 00144 and purified by adsorptive resin and reverse-phase column chromatography. This compound is a potent inhibitor of gluconeogenesis and is a promising candidate of anti-diabetic agent.

Hintoniamine, a new calmodulin inhibitor from the endophytic fungal species 39140-2

USDA-ARS?s Scientific Manuscript database

A new fungal endophytic species (39140-2) was isolated from the medicinal plant Hintonia latiflora (Sessé et Mociño ex DC.) Bullock, a Rubiaceae widely used in Mexico as antidiabetic agent. Sequencing of the 28S fraction of the rDNA of this fungal strain and comparing with similar sequences for all ...

Semaglutide for type 2 diabetes mellitus: a systematic review and meta-analysis.

PubMed

Andreadis, Panagiotis; Karagiannis, Thomas; Malandris, Konstantinos; Avgerinos, Ioannis; Liakos, Aris; Manolopoulos, Apostolos; Bekiari, Eleni; Matthews, David R; Tsapas, Apostolos

2018-05-13

To assess the efficacy and safety of semaglutide, a recently approved glucagon-like peptide 1 receptor agonist (GLP-1 RA) for type 2 diabetes. We searched major electronic databases and grey literature sources for randomised controlled trials comparing semaglutide with placebo or other antidiabetic agents. Primary outcome was change from baseline in HbA 1c . Secondary endpoints included change from baseline in body weight, blood pressure, heart rate, and incidence of hypoglycaemia, gastrointestinal adverse effects, pancreatitis and diabetic retinopathy. Six placebo-controlled and seven active-controlled studies with subcutaneous semaglutide were included. We identified only one trial with oral semaglutide. Compared with placebo, subcutaneous semaglutide 0.5 and 1 mg reduced HbA 1c by 1.01% (95% CI 0.56 to 1.47) and 1.38% (1.05 to 1.70) respectively. Both doses demonstrated superior glycaemic efficacy compared to other antidiabetic agents, including sitagliptin, exenatide, liraglutide, dulaglutide and insulin glargine. Semaglutide also had a beneficial effect on body weight (mean difference versus placebo -4.11 kg, 95% CI -4.85 to -3.37 for semaglutide 1 mg) and systolic blood pressure. We did not observe increased hypoglycaemia rates with semaglutide; nevertheless, we noted an increased incidence of nausea, vomiting and diarrhoea. Cases of pancreatitis were infrequent and odds ratio for diabetic retinopathy compared with placebo was 1.32 (95% CI 0.98 to 1.77). Semaglutide is a potent once-weekly GLP-1 RA, reducing significantly HbA 1c , body weight and systolic blood pressure. However, it is associated with increased incidence of gastrointestinal adverse events. Results for pancreatitis and retinopathy require further assessment in post-approval pharmacovigilance studies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Antidiabetic therapies and male reproductive function: where do we stand?

PubMed

Tavares, R S; Escada-Rebelo, S; Silva, A F; Sousa, M I; Ramalho-Santos, J; Amaral, S

2018-01-01

Diabetes mellitus has been increasing at alarming rates in recent years, thus jeopardizing human health worldwide. Several antidiabetic drugs have been introduced in the market to manage glycemic levels, and proven effective in avoiding, minimizing or preventing the appearance or development of diabetes mellitus-related complications. However, and despite the established association between such pathology and male reproductive dysfunction, the influence of these therapeutic interventions on such topics have been scarcely explored. Importantly, this pathology may contribute toward the global decline in male fertility, giving the increasing preponderance of diabetes mellitus in young men at their reproductive age. Therefore, it is mandatory that the reproductive health of diabetic individuals is maintained during the antidiabetic treatment. With this in mind, we have gathered the available information and made a critical analysis regarding the effects of several antidiabetic drugs on male reproductive function. Unlike insulin, which has a clear and fundamental role on male reproductive function, the other antidiabetic therapies' effects at this level seem incoherent. In fact, studies are highly controversial possibly due to the different experimental study approaches, which, in our opinion, suggests caution when it comes to prescribing such drugs to young diabetic patients. Overall, much is still to be determined and further studies are needed to clarify the safety of these antidiabetic strategies on male reproductive system. Aspects such as the effects of insulin levels variations, consequent of insulin therapy, as well as what will be the impact of the side effect hypoglycemia, common to several therapeutic strategies discussed, on the male reproductive system are still to be addressed. © 2018 Society for Reproduction and Fertility.

Diabetes mellitus: An overview on its pharmacological aspects and reported medicinal plants having antidiabetic activity

PubMed Central

Patel, DK; Kumar, R; Laloo, D; Hemalatha, S

2012-01-01

Diabetes mellitus is not a single disease but is a group of metabolic disorders affecting a huge number of population in the world. It is mainly characterized by chronic hyperglycemia, resulting from defects in insulin secretion or insulin action. It is predicated that the number of diabetes person in the world could reach upto 366 million by the year 2030. Even though the cases of diabetes are increasing day by day, except insulin and oral hypoglycemic drugs no other way of treatment has been successfully developed so far. Thus, the objective of the present review is to provide an insight over the pathophysiological and etiological aspects of diabetes mellitus along with the remedies available for this metabolic disorder. The review also contains brief idea about diabetes mellitus and the experimental screening model with their relevant mechanism and significance mainly used nowadays. Alloxan and streptozotocin are mainly used for evaluating the antidiabetic activity of a particular drug. This review contain list of medicinal plants which have been tested for their antidiabetic activity in the alloxan induced diabetic rat model. From the available data in the literature, it was found that plant having antidiabetic activity is mainly due to the presence of the secondary metabolite. Thus, the information provided in this review will help the researchers for the development of an alternative methods rather than insulin and oral hypoglycemic agents for the treatment of diabetes mellitus, which will minimize the complication associated with the diabetes and related disorder. PMID:23569941

Identification of Novel Human Dipeptidyl Peptidase-IV Inhibitors of Natural Origin (Part II): In Silico Prediction in Antidiabetic Extracts

PubMed Central

Guasch, Laura; Sala, Esther; Ojeda, María José; Valls, Cristina; Bladé, Cinta; Mulero, Miquel; Blay, Mayte; Ardévol, Anna; Garcia-Vallvé, Santiago; Pujadas, Gerard

2012-01-01

Background Natural extracts play an important role in traditional medicines for the treatment of diabetes mellitus and are also an essential resource for new drug discovery. Dipeptidyl peptidase IV (DPP-IV) inhibitors are potential candidates for the treatment of type 2 diabetes mellitus, and the effectiveness of certain antidiabetic extracts of natural origin could be, at least partially, explained by the inhibition of DPP-IV. Methodology/Principal Findings Using an initial set of 29,779 natural products that are annotated with their natural source and an experimentally validated virtual screening procedure previously developed in our lab (Guasch et al.; 2012) [1], we have predicted 12 potential DPP-IV inhibitors from 12 different plant extracts that are known to have antidiabetic activity. Seven of these molecules are identical or similar to molecules with described antidiabetic activity (although their role as DPP-IV inhibitors has not been suggested as an explanation for their bioactivity). Therefore, it is plausible that these 12 molecules could be responsible, at least in part, for the antidiabetic activity of these extracts through their inhibitory effect on DPP-IV. In addition, we also identified as potential DPP-IV inhibitors 6 molecules from 6 different plants with no described antidiabetic activity but that share the same genus as plants with known antidiabetic properties. Moreover, none of the 18 molecules that we predicted as DPP-IV inhibitors exhibits chemical similarity with a group of 2,342 known DPP-IV inhibitors. Conclusions/Significance Our study identified 18 potential DPP-IV inhibitors in 18 different plant extracts (12 of these plants have known antidiabetic properties, whereas, for the remaining 6, antidiabetic activity has been reported for other plant species from the same genus). Moreover, none of the 18 molecules exhibits chemical similarity with a large group of known DPP-IV inhibitors. PMID:23028712

Filarial Abundant Larval Transcript Protein ALT-2: An Immunomodulatory Therapeutic Agent for Type 1 Diabetes.

PubMed

Reddy, Sridhar M; Reddy, Pooja M; Amdare, Nitin; Khatri, Vishal; Tarnekar, Aaditya; Goswami, Kalyan; Reddy, Maryada Venkata Rami

2017-03-01

Type 1 diabetes (T1D) that accounts for about 5-10 % of all diabetes cases results from the autoimmune destruction of the insulin-producing beta cells in the pancreas. It is characterized by severe inflammatory reaction mediated by pronounced T helper type-1 response. Parasitic infections having the ability to skew the host immune responses towards type-2 type as a part of their defense mechanism are able to induce protection against autoimmune diseases like T1D. Hence, the present study is undertaken to explore a recombinant abundant larval transcript protein of the human lymphatic filarial parasite Brugia malayi ( rBm ALT-2), a known anti-inflammatory molecule for its therapeutic effect on streptozotocin (STZ)-induced T1D in mice. The diabetic mice on treatment with r Bm ALT-2 showed a significant ( p  < 0.0005) decrease in their fasting blood glucose levels. By the end of the second week after the initiation of treatment with the r Bm ALT-2, 28 % of the diabetic mice became normal and none of them were diabetic by the end of 5th week. The anti-diabetic effect of r Bm ALT-2 significantly correlated with the concomitant redressal of the pancreatic histopathological damage caused by STZ assault (rho = 0.87; p  < 0.0005). The sera of r Bm ALT-2 treated diabetic mice had increased levels of IgG1 antibodies associated with decreased IgG2a antibodies against the principal autoantigen insulin. The splenocyte proliferative response and the cytokine release in the treated mice showed marked bias against inflammation skewing the immune response to Th-2 type. From this study, it can be envisaged that that filarial proteins like r Bm ALT-2 with effective immunomodulatory activity and anti-diabetic effect are promising alternative therapeutic agents for T1D.

Comparison of the Chemical Profiles and Antioxidant and Antidiabetic Activities of Extracts from Two Ganoderma Species (Agaricomycetes).

PubMed

Tang, Xiaoqing; Cai, Weixi; Xu, Baojun

2016-01-01

The objective of this study was to compare the mycochemical profiles, antioxidant activities, and antidiabetic effects of 2 species of genus Ganoderma, the red lingzhi (G. lucidum) and purple lingzhi (G. sinense) mushrooms. In Chinese medicinal practice, hot water and ethanol are used as solvents to extract samples. In this study, a total of 4 extracts (ethanol and hot water extracts from G. lucidum and G. sinense) were prepared for further assays. Hot water extracts presented much higher values for total phenolic content and ferric-reducing antioxidant power than the ethanol extracts. Ethanol (70%) extract of G. lucidum had the strongest α-glycosidase inhibitory capacity, but the lingzhi polysaccharides showed no inhibitory effect. It also had the largest amount of total ganoderic acids. The results indicated that ethanol extracts from both G. lucidum and G. sinense showed better antidiabetic effects than the hot water extracts. Ganoderic acids, rather than polysaccharides, may contribute the antidiabetic effects of both the Ganoderma species.

Antidiabetic effect of total flavonoids from Sanguis draxonis in type 2 diabetic rats.

PubMed

Chen, Fufeng; Xiong, Hui; Wang, Jianxia; Ding, Xin; Shu, Guangwen; Mei, Zhinan

2013-10-07

Sanguis draxonis (SD) is a kind of red resin obtained from the wood of Dracaena cochinchinensis (Lour.) S. C. Chen (Dracaena cochinchinensis). It is a Chinese traditional herb that is prescribed for the handling of diabetic disorders, which is also supported by an array of scientific studies published in recent years. Although chemical constituents of this plant material have also been previously evaluated (Tang et al., 1995; Wei et al., 1998), it still remains poorly understood which constituent is the major contributor to its antidiabetic activities. Moreover, very little is known about the molecular mechanisms underlying antidiabetic activities of SD. Flavonoids exist at a high level in SD. The aim of this study is to evaluate the antidiabetic effects of total flavonoids from SD (SDF) in type 2 Diabetes mellitus (T2DM) rats. T2DM rats were induced by 4 weeks high-fat diet and a singular injection of streptozotocin (STZ) (35mg/kg). Then T2DM rats were treated with SDF for 21 days, using normal saline as the negative control. For comparison, a standard antidiabetic drug, metformin (200mg/kg), was used as a positive control. Three weeks later, relative biochemical indexes were determined and histopathological examinations were performed to assess the antidiabetic activities of SDF. SDF not only exhibited a significant hypoglycemic activity, but also alleviated dyslipidemia, tissue steatosis, and oxidative stress associated with T2DM. Moreover, considerable pancreatic islet protecting effects could be observed after SDF treatment. Further investigations revealed a potential anti-inflammation activity of SDF by determining serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). This study demonstrates both hypoglycemic and hypolipidemic effects of SDF in T2DM rats, suggesting that flavonoids are the major active ingredients accounting for the antidiabetic activity of SD. Alleviating chronic inflammation responses and protecting pancreatic islets are possible mechanisms involved in the antidiabetic activity of SDF. © 2013 Elsevier Ireland Ltd. All rights reserved.

Virtual identification of novel PPARα/γ dual agonists by scaffold hopping of saroglitazar.

PubMed

Jia, Wen-Qing; Jing, Zhi; Liu, Xin; Feng, Xiao-Yan; Liu, Ya-Ya; Wang, Shu-Qing; Xu, Wei-Ren; Liu, Jian-Wen; Cheng, Xian-Chao

2017-10-28

The thiazolidinedione class PPARγ agonists as antidiabetic agents are restricted in clinical use because of the side effects such as edema, weight gain, and heart failure. The single and selective agonism of PPARγ is the main cause of side effects. The multi-target cooperative PPARα/γ dual agonist development is a hot topic in the antidiabetic medicinal chemistry field. Saroglitazar is the first approved PPARα/γ dual agonist, available in India for the treatment of diabetic dyslipidemia. It got rid of these side effects. With the aim of finding more protent PPARα/γ dual agonists, the scaffold hopping was used to replace α-o phenylpropionic acid skeleton of saroglitazar with L-tyrosine skeleton. Then, the structural modification was carried out designing 72 compounds. Considering the importance of chirality, opposite configuration of 72 compounds was also studied. 12 compounds with better -cdocker energy were screened by molecular docking. Subsequently, the pharmacokinetic properties and toxicity evaluated by ADMET prediction, 11 of them showed better properties. Comp#L-17-1 and comp#L-3-1 were regarded as representatives to study the binding stability by molecular dynamics (MD) simulations. The MD simulation results of comp#L-17-1-PPARs (α, γ) and comp#L-3-1-PPARs (α, γ) provided structure reference for the research and development of novel PPARα/γ dual agonists.

Induced desensitization of the insulinotropic effects of antidiabetic drugs, BTS 67 582 and tolbutamide

PubMed Central

McClenaghan, Neville H; Ball, Andrew J; Flatt, Peter R

2000-01-01

Acute and chronic mechanisms of action of novel insulinotropic antidiabetic drug, BTS 67 582 (1,1-dimethyl-2-(2-morpholinophenyl)guanidine fumarate), were examined in the stable cultured BRIN-BD11 cell line. BTS 67 582 (100–400 μM) stimulated a concentration-dependent increase (P<0.01) in insulin release at both non-stimulatory (1.1 mM) and stimulatory (8.4 mM) glucose. Long-term exposure (3–18 h) to 100 μM BTS 67 582 in culture time-dependently decreased subsequent responsiveness to acute challenge with 200 μM BTS 67 582 or 200 μM tolbutamide at 12–18 h (P<0.001). Similarly 3–18 h culture with the sulphonylurea, tolbutamide (100 μM), also effectively suppressed subsequent insulinotropic responses to both BTS 67 582 and tolbutamide. Culture with 100 μM BTS 67 582 or 100 μM tolbutamide did not affect basal insulin secretion, cellular insulin content, or cell viability and exerted no influence on the secretory responsiveness to 200 μM of the imidazoline, efaroxan. While 18 h BTS 67 582 culture did not affect the insulin-releasing actions (P<0.001) of 16.7 mM glucose, 10 mM arginine, 30 mM KCl, 25 μM forskolin or 10 nM phorbol-12-myristate 13-acetate (PMA), significant inhibition (P<0.001) of the insulinotropic effects of 10 mM 2-ketoisocaproic acid (KIC) and 10 mM alanine were observed. These data suggest that BTS 67 582 shares a common signalling pathway to sulphonylurea but not imidazoline drugs. Desensitization of drug action may provide an important approach to dissect sites of action of novel and established insulinotropic antidiabetic agents. PMID:10807689

Updates on Managing Type 2 Diabetes Mellitus with Natural Products: Towards Antidiabetic Drug Development.

PubMed

Alam, Fahmida; Islam, Md Asiful; Kamal, M A; Gan, Siew Hua

2016-08-13

Over the years, natural products have shown success as antidiabetics in vitro, in vivo and in clinical trials. Because natural product-derived drugs are more affordable and effective with fewer side-effects compared to conventional therapies, pharmaceutical research is increasingly leaning towards the discovery of new antidiabetic drugs from natural products targeting pathways or components associated with type 2 diabetes mellitus (T2DM) pathophysiology. However, the drug discovery process is very lengthy and costly with significant challenges. Therefore, various techniques are currently being developed for the preclinical research phase of drug discovery with the aim of drug development with less time and efforts from natural products. In this review, we have provided an update on natural products including fruits, vegetables, spices, nuts, beverages and mushrooms with potential antidiabetic activities from in vivo, in vitro and clinical studies. Synergistic interactions between natural products and antidiabetic drugs; and potential antidiabetic active compounds from natural products are also documented to pave the way for combination treatment and new drug discovery, respectively. Additionally, a brief idea of the drug discovery process along with the challenges that arise during drug development from natural products and the methods to conquer those challenges are discussed to create a more convenient future drug discovery process.

Anti-diabetic effects of rice hull smoke extract in alloxan-induced diabetic mice

USDA-ARS?s Scientific Manuscript database

We investigated the protective effect of a liquid rice hull smoke extract (RHSE) against diabetes in alloxan-induced diabetic mice. Anti-diabetic effects of RHSE were evaluated in both the rat insulinoma-1 cell line (INS-1) and diabetic ICR mice induced by inraperitoneal (ip) injection of alloxan. ...

Antidiabetic Properties of Germinated Brown Rice: A Systematic Review

PubMed Central

Bhanger, Muhammad Iqbal; Ismail, Norsharina; Ismail, Maznah

2012-01-01

Diet is an important variable in the course of type 2 diabetes, which has generated interest in dietary options like germinated brown rice (GBR) for effective management of the disease among rice-consuming populations. In vitro data and animal experiments show that GBR has potentials as a functional diet for managing this disease, and short-term clinical studies indicate encouraging results. Mechanisms for antidiabetic effects of GBR due to bioactive compounds like γ-aminobutyric acid (GABA), γ-oryzanol, dietary fibre, phenolics, vitamins, acylated steryl β-glucoside, and minerals include antihyperglycemia, low insulin index, antioxidative effect, antithrombosis, antihypertensive effect, hypocholesterolemia, and neuroprotective effects. The evidence so far suggests that there may be enormous benefits for diabetics in rice-consuming populations if white rice is replaced with GBR. However, long-term clinical studies are still needed to verify these findings on antidiabetic effects of GBR. Thus, we present a review on the antidiabetic properties of GBR from relevant preclinical and clinical studies, in order to provide detailed information on this subject for researchers to review the potential of GBR in combating this disease. PMID:23304216

Pattern of pharmaceutical retailing of anti-diabetic products in Ibadan, Nigeria.

PubMed

Famuyiwa, O O

1991-01-01

Twenty-four pharmacists in the city of Ibadan were surveyed through a self-administered structured questionnaire as to the extent of their involvement in the pharmaceutical retailing of antidiabetic products and their cost. Oral hypoglycemic agents especially, chlorpropamide (Diabenese) and glibenclamide (Daonil) were the most readily available drugs being obtainable from 21 (87.5%) pharmacies. Insulin was stocked regularly by only 14 (58.3%) of the pharmacists and insulin syringes and needles could be obtained from only 10 (41.6%) of the pharmacies. Among materials for urine testing, clinistix strip was the most readily available and fully one-third of the pharmacies did not stock any such material. The prices of all the products were disturbingly high and between 1983 and 1986 when retail prices were re-assessed, the cost of some materials had escalated by as much as 400%. Scarcity of antidiabetic products and their high cost pose serious challenges for those involved in the care of diabetic patients in Nigeria. Some suggestions have been made as to what steps both the government and the pharmaceutical industry can take in ensuring the availability of these life sustaining products for the increasingly large Nigerian diabetic population.

The Role of Metformin in Metabolic Disturbances during Pregnancy: Polycystic Ovary Syndrome and Gestational Diabetes Mellitus

PubMed Central

Rojas, Joselyn; Chávez-Castillo, Mervin; Bermúdez, Valmore

2014-01-01

Maintenance of gestation implicates complex function of multiple endocrine mechanisms, and disruptions of the global metabolic environment prompt profound consequences on fetomaternal well-being during pregnancy and postpartum. Polycystic Ovary Syndrome (PCOS) and gestational diabetes mellitus (GDM) are very frequent conditions which increase risk for pregnancy complications, including early pregnancy loss, pregnancy-induced hypertensive disorders, and preterm labor, among many others. Insulin resistance (IR) plays a pivotal role in the pathogenesis of both PCOS and GDM, representing an important therapeutic target, with metformin being the most widely prescribed insulin-sensitizing antidiabetic drug. Although traditional views neglect use of oral antidiabetic agents during pregnancy, increasing evidence of safety during gestation has led to metformin now being recognized as a valuable tool in prevention of IR-related pregnancy complications and management of GDM. Metformin has been demonstrated to reduce rates of early pregnancy loss and onset of GDM in women with PCOS, and it appears to offer better metabolic control than insulin and other oral antidiabetic drugs during pregnancy. This review aims to summarize key aspects of current evidence concerning molecular and epidemiological knowledge on metformin use during pregnancy in the setting of PCOS and GDM. PMID:25763406

[Glucokinase and glucokinase regulatory proteins as molecular targets for novel antidiabetic drugs].

PubMed

Rubtsov, P M; Igudin, E L; Tiulpakov, A N

2015-01-01

The impairment of glucose homeostasis leads to hyperglycemia and type-2 diabetes mellitus. Glucokinase (GK), an enzyme that catalyzes the conversion of glucose to glucose-6-phosphate in pancreatic ß-cells, liver hepatocytes, specific hypothalamic neurons, and intestine enterocytes, is a key regulator of glucose homeostasis. In hepatocytes, GK controls the glucose uptake and glycogen synthesis and inhibits the glucose synthesis via the gluconeogenesis pathway. Glucokinase regulatory protein (GKRP) synthesized in hepatocytes acts as an endogenous GK inhibitor. During fasting, GKRP binds GK, inactivates it, and transports it into the cell nucleus, thus isolating it from the hepatocyte carbohydrate metabolism. In the beginning of the 2000s, the research was mainly focused on the development and trials of the small molecule GK activators as potential antidiabetic glucose-lowering drugs. However, the use of such substances increased the risk of hypoglycemia, and clinical studies of most synthetic GK activators are currently discontinued. Allosteric inhibitors of the GK-GKRP interaction are coming as alternative agents increasing the GK activity that can substitute GKA. In this review, we discuss the recent advances and the current state of art in the development of potential antidiabetic drugs targeted to GK as a key regulator of glucose homeostasis.

Synthesis, pharmacological evaluation and molecular docking studies of pyrimidinedione based DPP-4 inhibitors as antidiabetic agents

NASA Astrophysics Data System (ADS)

Jha, Vibhu; Bhadoriya, Kamlendra Singh

2018-04-01

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of newly developed antidiabetic drugs that bock DPP-4. DPP-4 is responsible for degradation of incretins harmones such as GLP-1 (Glucagon like Peptide) and GIP (Gastric inhibitory polypeptide) that maintain blood-glucose level. Pyrimidinedione based compounds were designed and synthesized for DPP-4 inhibitory activity. These heterocycles were designed by taking Alogliptin as a reference DPP-4 inhibitors and synthesized as N-methylated and N-benzylated pyrimidinediones. These compounds were subjected to DPP-4 assay, five out of nine synthesized compounds have shown in vitro DPP-4 inhibitory activity in significant range. Further, molecular docking studies of these compounds were performed on DPP-4 subunit and compared with natural DPP-4 inhibitors like Flavone, Resveratrol, Quercetin, Diprotin A. Docking studies have led to the conclusion that there are some identical amino acid interactions as Tyr 666 and Tyr 662, seen in both synthesized compounds and natural DPP-4 inhibitors. This study completely gives a good scope for further derivatisation and optimization of synthesized compounds to get clinical candidate as DPP-4 inhibitor for antidiabetic activity.

Assessment of DNA damage and lipid peroxidation in diabetic mice: effects of propolis and epigallocatechin gallate (EGCG).

PubMed

Oršolić, Nada; Sirovina, Damir; Gajski, Goran; Garaj-Vrhovac, Vera; Jazvinšćak Jembrek, Maja; Kosalec, Ivan

2013-09-18

There is growing recognition that polyphenolic compounds present in many plants and natural products may have beneficial effects on human health. Propolis - a substance produced by honeybees - and catechins in tea, in particular (-)-epigallocatechin gallate (EGCG), are strong antioxidants that appear to have anti-obesity and anti-diabetic effects. The present study was designed to elucidate the anti-diabetic effect of the water-soluble derivative of propolis (WSDP), which contains phenolic acids as the main compounds, and EGCG in alloxan-induced (75mg/kg, iv) diabetes in mice. Intraperitoneal administration of EGCG or propolis at doses of 50mg/kg body weight (bw) to diabetic mice for a period of 7 days resulted in a significant increase in body weight and in haematological/immunological blood parameters, as well as in 100% survival of the mice. A significant decrease in lipid peroxidation in liver, kidney and brain tissue was also observed in diabetic mice treated with these two agents. Additionally, EGCG and propolis clearly reduced DNA damage in peripheral lymphocytes of diabetic mice. Our studies demonstrate the anti-oxidative and anti-inflammatory potential of WSDP and EGCG, which could exert beneficial effects against diabetes and the associated consequences of free-radical formation in kidney, liver, spleen and brain tissue. The results suggest that dietary supplementation with WSDP or EGCG could potentially contribute to nutritional strategies for the prevention and treatment of diabetes mellitus. Copyright © 2013 Elsevier B.V. All rights reserved.

CoMFA and CoMSIA studies on C-aryl glucoside SGLT2 inhibitors as potential anti-diabetic agents.

PubMed

Vyas, V K; Bhatt, H G; Patel, P K; Jalu, J; Chintha, C; Gupta, N; Ghate, M

2013-01-01

SGLT2 has become a target of therapeutic interest in diabetes research. CoMFA and CoMSIA studies were performed on C-aryl glucoside SGLT2 inhibitors (180 analogues) as potential anti-diabetic agents. Three different alignment strategies were used for the compounds. The best CoMFA and CoMSIA models were obtained by means of Distill rigid body alignment of training and test sets, and found statistically significant with cross-validated coefficients (q²) of 0.602 and 0.618, respectively, and conventional coefficients (r²) of 0.905 and 0.902, respectively. Both models were validated by a test set of 36 compounds giving satisfactory predicted correlation coefficients (r² pred) of 0.622 and 0.584 for CoMFA and CoMSIA models, respectively. A comparison was made with earlier 3D QSAR study on SGLT2 inhibitors, which shows that our 3D QSAR models are better than earlier models to predict good inhibitory activity. CoMFA and CoMSIA models generated in this work can provide useful information to design new compounds and helped in prediction of activity prior to synthesis.

Identification of PPARgamma Partial Agonists of Natural Origin (II): In Silico Prediction in Natural Extracts with Known Antidiabetic Activity

PubMed Central

Guasch, Laura; Sala, Esther; Mulero, Miquel; Valls, Cristina; Salvadó, Maria Josepa; Pujadas, Gerard; Garcia-Vallvé, Santiago

2013-01-01

Background Natural extracts have played an important role in the prevention and treatment of diseases and are important sources for drug discovery. However, to be effectively used in these processes, natural extracts must be characterized through the identification of their active compounds and their modes of action. Methodology/Principal Findings From an initial set of 29,779 natural products that are annotated with their natural source and using a previously developed virtual screening procedure (carefully validated experimentally), we have predicted as potential peroxisome proliferators-activated receptor gamma (PPARγ) partial agonists 12 molecules from 11 extracts known to have antidiabetic activity. Six of these molecules are similar to molecules with described antidiabetic activity but whose mechanism of action is unknown. Therefore, it is plausible that these 12 molecules could be the bioactive molecules responsible, at least in part, for the antidiabetic activity of the extracts containing them. In addition, we have also identified as potential PPARγ partial agonists 10 molecules from 16 plants with undescribed antidiabetic activity but that are related (i.e., they are from the same genus) to plants with known antidiabetic properties. None of the 22 molecules that we predict as PPARγ partial agonists show chemical similarity with a group of 211 known PPARγ partial agonists obtained from the literature. Conclusions/Significance Our results provide a new hypothesis about the active molecules of natural extracts with antidiabetic properties and their mode of action. We also suggest plants with undescribed antidiabetic activity that may contain PPARγ partial agonists. These plants represent a new source of potential antidiabetic extracts. Consequently, our work opens the door to the discovery of new antidiabetic extracts and molecules that can be of use, for instance, in the design of new antidiabetic drugs or functional foods focused towards the prevention/treatment of type 2 Diabetes Mellitus. PMID:23405231

New amides from seeds of Silybum marianum with potential antioxidant and antidiabetic activities.

PubMed

Qin, Ning-Bo; Jia, Cui-Cui; Xu, Jun; Li, Da-Hong; Xu, Fan-Xing; Bai, Jiao; Li, Zhan-Lin; Hua, Hui-Ming

2017-06-01

Two new amide compounds, mariamides A and B (1-2), were obtained together with fourteen known compounds from the seeds of milk thistle (Silybum marianum). Their structures were established on the basis of extensive 1D and 2D NMR analyses, as well as HR-ESI-MS data. Most of the compounds showed significant antioxidant activities than positive control in ABTS and FRAP assays. However, only amide compounds 1-4 showed moderate DPPH radical scavenging activity and compounds 7 and 16 showed the most potent activity against DPPH. Most of the compounds showed moderate to stronger α-glucosidase inhibitory activities. Nevertheless, only flavonoids showed strong PTP1B inhibitory activities. These results indicate a use of milk thistle seed extracts as promising antioxidant and antidiabetic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

SGLT2-inhibitors: a novel class for the treatment of type 2 diabetes introduction of SGLT2-inhibitors in clinical practice.

PubMed

Cuypers, J; Mathieu, C; Benhalima, K

2013-01-01

Treatment of type 2 diabetes (T2DM) continues to present challenges, with significant proportion of patients failing to achieve and maintain glycemic targets. Despite the availability of many oral antidiabetic agents, therapeutic efficacy is offset by side effects such as weight gain and hypoglycemia. Therefore, the search for novel therapeutic agents with an improved benefit-risk profile continues. Recent research has focused on the kidney as a potential therapeutic target, especially because maximal renal glucose reabsorption is increased in T2DM. Under normal physiological conditions, nearly all filtered glucose is reabsorbed in the proximal tubule of the nephron, principally via the sodium-glucose cotransporter 2 (SGLT2). SGLT2-inhibitors are a new class of oral antidiabetics, which reduce hyperglycemia by increasing urinary glucose excretion independently of insulin secretion or action. Clinical results are promising with significant lowering of HbA1c without increased risk of hypoglycemia, reduction of body weight and reduction of systolic blood pressure. Dapagliflozin is the first highly selective SGLT2-inhibitor approved by the European Medecine Agency. Canagliflozin and empagliflozin are undergoing phase III trials. Actual safety issues are an increased risk for genital- and urinary tract infections and a possible increased risk for bladder and breast cancer. This led to refusal of dapagliflozin by the Food and Drug Administration (FDA). A large randomized control trial is therefore warranted by the FDA. This review provides an overview of the current evidence available so far on the therapeutic potential of the SGLT2-inhibitors for the treatment of T2DM.

Resource utilization with insulin pump therapy for type 2 diabetes mellitus.

PubMed

Lynch, Peter M; Riedel, Aylin Altan; Samant, Navendu; Fan, Ying; Peoples, Tim; Levinson, Jennifer; Lee, Scott W

2010-01-01

To evaluate the effects of switching from multiple daily injection (MDI) therapy to insulin pump therapy, also called continuous subcutaneous insulin infusion (CSII), on antidiabetic drug and healthcare resource utilization. This study was a retrospective analysis of administrative claims data from a large geographically diverse health plan in the United States from January 1, 2005, through April 30, 2008. Changes in antidiabetic drug use, antidiabetic drug switching and augmentation, and healthcare utilization during the baseline period and after CSII initiation were assessed using paired t test. There were 3649 possible subjects, of whom 943 met the criteria for analysis. The mean number of antidiabetic drugs used decreased by 46% after CSII initiation, and the mean reduction in antidiabetic drug utilization was 0.67; both were statistically significant. More than one-third of subjects who were taking antidiabetic drugs before CSII initiation discontinued oral therapy after CSII initiation. The number of subjects using multiple antidiabetic drugs significantly decreased after CSII initiation by 58%, and rates of switching or augmenting significantly decreased from 42% at baseline to 25% after CSII initiation.The rates of emergency department visits and inpatient admissions significantly decreased, and the rate of ambulatory visits significantly increased. CSII was associated with significant decreases in antidiabetic drug and healthcare resource utilization, contributing to stability of care. The evidence from this study indicates that CSII should be considered as an option for patients with type 2 diabetes mellitus who are using MDI and are experiencing a high degree of antidiabetic drug and healthcare resource utilization.

Psidium cattleianum fruits: A review on its composition and bioactivity.

PubMed

Dos Santos Pereira, Elisa; Vinholes, Juliana; C Franzon, Rodrigo; Dalmazo, Gabriel; Vizzotto, Márcia; Nora, Leonardo

2018-08-30

Psidium cattleianum Sabine, commonly known as araçá, is a Brazilian native fruit, which is very juicy, with sweet to sub acid pulp and a spicy touch. The fruit can be eaten fresh or processed into juice, jellies and ice creams. Araçás are source of vitamin C, minerals, fatty acids, polysaccharides, volatile compounds, carotenoids and phenolic compounds, which can provide nutrients and phytochemical agents with different biological functions. Different pharmacological studies demonstrate that P. cattleianum exerts antioxidant, antidiabetic, anticarcinogenic, antimicrobial, anti-inflammatory and antiaging effects. Thus, this article aims to review the chemical composition and biological effects reported for araçá fruit in the last years. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identification of Antidiabetic Compounds from Polyphenolic-rich Fractions of Bulbine abyssinica A. Rich Leaves

PubMed Central

Odeyemi, Samuel Wale; Afolayan, Anthony Jiede

2018-01-01

Background: Bulbine abyssinica has been reported to possess a variety of pharmacological activities traditionally. Previous work suggested its antidiabetic properties, but information on the antidiabetic compounds is still lacking. Objective: The present research exertion was aimed to isolate and identify biologically active polyphenols from B. abyssinica leaves and to evaluate their efficacy on carbohydrate digesting enzymes. Materials and Methods: Fractionation of the polyphenolic contents from the methanolic extract of B. abyssinica leaves was executed by the silica gel column chromatography to yield different fractions. The antioxidant activities of these fractions were carried out against 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS), 2,2-diphenyl-1-picrylhydrazyl radicals, and ferric ion-reducing antioxidant power (FRAP). In vitro antidiabetic experimentation was performed by evaluating the α-amylase and α-glucosidase inhibitory capacity. The isolated polyphenols were then identified using liquid chromatography and mass spectroscopy (LC/MS). Results: Out of the eight polyphenolic fractions (BAL 1–8), BAL-4 has the highest inhibitory activity against ABTS radicals whereas BAL-6 showed potent ferric ion-reducing capacity. BAL-5 was the most effective fraction with antidiabetic activity with IC50of 140.0 and 68.58 ± 3.2 μg/ml for α-amylase and α-glucosidase inhibitory activities, respectively. All the fractions competitively inhibited α-amylase, BAL-5 and BAL-6 also inhibited α-glucosidase competitively, while BAL-4 and BAL-1 exhibited noncompetitive and near competitive inhibitions against α-glucosidase, respectively. The LC/MS analysis revealed the presence of carvone in all the fractions. Conclusions: The present study demonstrates the antioxidant and antidiabetic activities of the isolated polyphenols from B. abyssinica. SUMMARY Polyphenols were successfully isolated and identified from Bulbine abyssinica leavesThe isolated polyphenols are biologically active with high antioxidant as well as inhibitor of carbohydrate-digesting enzymesB. abyssinica can be a good source of amylase and glucosidase inhibitorsB. abyssinica can be used as complementary or alternative therapeutic agents especially for the treatment of diabetesCarvone, quercetin, and psoralen could be the compounds responsible for the α-amylase and α-glucosidase inhibitory activities. Abbreviations Used: ABTS: 2,2'-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), DPPH: 2,2-diphenyl-1-picrylhydrazyl, FRAP: Ferric ion-reducing antioxidant power, LC/MS: Liquid chromatography and mass spectroscopy, AGEs: Advanced glycation end products, TLC: Thin-layer chromatography, MeOH: Methanol, PNP-G: ρ-Nitrophenyl-α-D-Glucoside, R2: Coefficient of determination, mgQE: Milligram quercetin equivalent, mgTAE: Milligram tannic acid equivalent, mgCE: Milligram catechin equivalent, g: Gram PMID:29568191

Oral antidiabetic therapy in a large Italian sample: drug supply and compliance for different therapeutic regimens.

PubMed

Vittorino Gaddi, A; Benedetto, D; Capello, F; Di Pietro, C; Cinconze, E; Rossi, E; De Sando, V; Cevenini, M; D'Alò, G

2014-01-01

To define the main features of patients treated with oral antidiabetics, evaluating monotherapy (MT), loose-dose combination therapy (LDCT) and fixed-dose combination therapy (FDCT); to describe medication adherence to the different therapies; and to evaluate the differences in compliance with the prescribed therapy regimen among prevalent and incident patient cohorts. This study was a retrospective cohort analysis based on the ARNO database, a national record that tracks reimbursable prescription claims submitted from selected pharmacies to the Italian national health system. In total, 169,375 subjects, from an overall population of 4,040,624 were included in this study. The patients represented 12 different local health units. Each patient had at least one oral antidiabetic prescription claim (A10B ATC code). Patients were divided into four groups according to their treatment regimen during the recruitment period (1 January 2008-31 December 2008): MT, FDCT, LDCT and switching therapy. A timespan of 5 years was considered, from 4 years before to 1 year after the index date (i.e. date of the prescription selected in the recruitment period). A medication possession ratio (MPR) with a cut-off value of 80% was used to measure medication adherence. Descriptive statistics and multiple logistic regression were used to define the objectives, while P < 0.05 was considered to indicate significance. The median age of patients (n = 169,375, prevalence 4.2%) was 70 years [interquartile range (IQR) 17], and 49.1% were females. Considering the entire sample, the median MPRs for the treatment regimens were: MT, 0.73 (IQR 0.53; 43.9% compliant); FDCT, 1 (IQR 0.29, 68,5% compliant); and LDCT, 0.89 (IQR 0.33, 60.3% compliant). FDCT and LDCT were significantly correlated with MPR. Compliance was 48.9% in the prevalent patient cohort (i.e. patients prescribed oral antidiabetic therapy in both prerecruitment and recruitment periods); median MPRs for the treatment regimens were: MT, 0.73 (IQR 0.52); FDCT, 1 (IQR 0.28); and LDCT, 0.90 (IQR 0.32). Compliance was 43.0% in the incident patient cohort (i.e. patients who were first prescribed oral antidiabetic therapy in the recruitment period); median MPRs for the treatment regimens were: MT, 0.70 (IQR, 0.58); FDCT, 1 (IQR 0.34); and LDCT, 0.64 (IQR 0.39). Compliance was better for FDCT than the other therapeutic regimens in the study population. The same trend was observed in both the prevalent and incident patient cohorts. As type 2 diabetes is a chronic lifelong pathology, and multiple agents are often required to achieve glycaemic control, the preference for FDCT in the population, when clinically applicable, could be an effective strategy for functional administration of clinical outcome and sources. Evaluation of specific population fractions (age, sex, compliance, etc.) and specific agents or drug combinations could also be relevant in order to reach the healthcare objectives. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats

PubMed Central

Qinna, Nidal A; Badwan, Adnan A

2015-01-01

Streptozotocin (STZ) is currently the most used diabetogenic agent in testing insulin and new antidiabetic drugs in animals. Due to the toxic and disruptive nature of STZ on organs, apart from pancreas, involved in preserving the body’s normal glucose homeostasis, this study aims to reassess the action of STZ in inducing different glucose response states in diabetic rats while testing insulin. Diabetic Sprague-Dawley rats induced with STZ were classified according to their initial blood glucose levels into stages. The effect of randomizing rats in such a manner was investigated for the severity of interrupting normal liver, pancreas, and kidney functions. Pharmacokinetic and pharmacodynamic actions of subcutaneously injected insulin in diabetic and nondiabetic rats were compared. Interruption of glucose homeostasis by STZ was challenged by single and repeated administrations of injected insulin and oral glucose to diabetic rats. In diabetic rats with high glucose (451–750 mg/dL), noticeable changes were seen in the liver and kidney functions compared to rats with lower basal glucose levels. Increased serum levels of recombinant human insulin were clearly indicated by a significant increase in the calculated maximum serum concentration and area under the concentration–time curve. Reversion of serum glucose levels to normal levels pre- and postinsulin and oral glucose administrations to STZ diabetic rats were found to be variable. In conclusion, diabetic animals were more responsive to insulin than nondiabetic animals. STZ was capable of inducing different levels of normal glucose homeostasis disruption in rats. Both pharmacokinetic and pharmacodynamic actions of insulin were altered when different initial blood glucose levels of STZ diabetic rats were selected for testing. Such findings emphasize the importance of selecting predefined and unified glucose levels when using STZ as a diabetogenic agent in experimental protocols evaluating new antidiabetic agents and insulin delivery systems. PMID:26005328

Glycemic control and antidiabetic drugs in type 2 diabetes mellitus patients with renal complications

PubMed Central

Huri, Hasniza Zaman; Lim, Lay Peng; Lim, Soo Kun

2015-01-01

Background Good glycemic control can delay the progression of kidney diseases in type 2 diabetes mellitus (T2DM) patients with renal complications. To date, the association between antidiabetic agents and glycemic control in this specific patient population is not well established. Purpose This study aimed to identify antidiabetic regimens as well as other factors that associated with glycemic control in T2DM patients with different stages of chronic kidney disease (CKD). Patients and methods This retrospective, cross-sectional study involved 242 T2DM inpatients and outpatients with renal complications from January 2009 to March 2014 and was conducted in a tertiary teaching hospital in Malaysia. Glycated hemoglobin (A1C) was used as main parameter to assess patients’ glycemic status. Patients were classified to have good (A1C <7%) or poor glycemic control (A1C ≥7%) based on the recommendations of the American Diabetes Association. Results Majority of the patients presented with CKD stage 4 (43.4%). Approximately 55.4% of patients were categorized to have poor glycemic control. Insulin (57.9%) was the most commonly prescribed antidiabetic medication, followed by sulfonylureas (43%). Of all antidiabetic regimens, sulfonylureas monotherapy (P<0.001), insulin therapy (P=0.005), and combination of biguanides with insulin (P=0.038) were found to be significantly associated with glycemic control. Other factors including duration of T2DM (P=0.004), comorbidities such as anemia (P=0.024) and retinopathy (P=0.033), concurrent medications such as erythropoietin therapy (P=0.047), α-blockers (P=0.033), and antigouts (P=0.003) were also correlated with A1C. Conclusion Identification of factors that are associated with glycemic control is important to help in optimization of glucose control in T2DM patients with renal complication. PMID:26300627

In vitro and in vivo antidiabetic potential of extracts and a furostanol saponin from Balanites aegyptiaca.

PubMed

Ezzat, Shahira Mohammed; Abdel Motaal, Amira; El Awdan, Sally Abdel Wanees

2017-12-01

Balanites aegyptiaca Del. (Zygophyllaceae) fruits are well-known antidiabetic drug in Egyptian folk medicine. Nevertheless, its mechanism of action is still unclear. Searching for the possible mechanisms of action of the plant and identification of its bioactive compounds. A bio-guided protocol based on the evaluation of α-glucosidase (AG) and aldose reductase (AR) inhibitory activities was adopted to isolate the biologically active compounds from the methanol extract (MeEx). An in vivo antidiabetic study was conducted for the active extract, fraction and compound using streptozotocin-induced diabetic male albino Wistar rats at two dose levels (100 and 200 mg/kg.b/wt) for 2 weeks. Three compounds were isolated and identified: a sterol, (1) stigmasterol-3-O-β-d-glucopyranoside; a pregnane glucoside, (2) pregn-5-ene-3β,16β,20(R)-trio1-3-O-β-d-glucopyranoside; a furostanol saponin, (3) 26-(O-β-d-glucopyranosyl)-22-O-methylfurost-5-ene-3β,26-diol-3-O-β-d-glucopyranosyl-(1 → 4)-[α-l-rhamnopyranosyl-(1 → 2)]-β-d-glucopyranoside. Only compound 3 possessed significant AG and AR inhibitory activities (IC 50  = 3.12 ± 0.17 and 1.04 ± 0.02 μg/mL, respectively), while compounds 1 and 2 were inactive. The in vivo antidiabetic study revealed that MeEx and furostanol saponin 3 possessed significant activities at a dose of 200 mg/kg through reducing the fasting plasma glucose level by 46.14% and 51.39%, respectively, as well as reducing the total cholesterol by 24.44% and 31.90%, respectively. Compound 3 also caused increment in insulin and C-peptide levels by 63.56% and 65%, respectively. We presented a scientific base for using Balanites aegyptiaca, and shed the light on one of its saponins, as an antidiabetic agent in fasting and postprandial hyperglycaemia along with the improvement of diabetic complications.

Antidiabetic effects of Justicia spicigera Schltdl (Acanthaceae).

PubMed

Ortiz-Andrade, Rolffy; Cabañas-Wuan, Angel; Arana-Argáez, Víctor E; Alonso-Castro, Angel Josabad; Zapata-Bustos, Rocio; Salazar-Olivo, Luis A; Domínguez, Fabiola; Chávez, Marco; Carranza-Álvarez, Candy; García-Carrancá, Alejandro

2012-09-28

Justicia spicigera is a plant species used for the Teenak (Huesteca Potosina) and Mayan (Yucatan peninsula) indigenous for the empirical treatment of diabetes, infections and as stimulant. To evaluate the cytotoxicity, antioxidant and antidiabetic properties of J. spicigera. The effects of ethanolic extracts of J. spicigera (JSE) on the glucose uptake in insulin-sensitive and insulin-resistant murine 3T3-F442A and human subcutaneous adipocytes was evaluated. The antioxidant activities of the extract of JSE was determined by ABTS and DPPH methods. Additionally, it was evaluated the antidiabetic properties of JSE on T2DM model. JSE stimulated 2-NBDG uptake by insulin-sensitive and insulin-resistant human and murine adipocytes in a concentration-dependent manner with higher potency than rosiglitazone 1mM. JSE showed antioxidant effects in vitro and induced glucose lowering effects in normoglycemic and STZ-induced diabetic rats. The antidiabetic effects of administration of J. spicigera are related to the stimulation of glucose uptake in both insulin-sensitive and insulin-resistant murine and human adipocytes and this evidence justify its empirical use in Traditional Medicine. In addition, J. spicigera exerts glucose lowering effects in normoglycemic and STZ-induced diabetic rats. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Black Seed (Nigella Sativa) and its Constituent Thymoquinone as an Antidote or a Protective Agent Against Natural or Chemical Toxicities

PubMed Central

Tavakkoli, Alireza; Ahmadi, Ali; Razavi, Bibi Marjan; Hosseinzadeh, Hossein

2017-01-01

Nigella sativa (N. sativa), which belongs to the botanical family of Ranunculaceae, is a widely used medicinal plant all over the world. N. sativa seeds and oil have been used in the treatment of different diseases. Various studies on N. sativa have been carried out and a broad spectrum of its pharmacological actions have been established which include antioxidant, antidiabetic, anticancer, antitussive, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, and bronchodilator. This is also indicated that the majority of the therapeutic effects of N. sativa are due to the presence of thymoquinone (TQ) that is the main bioactive constituent of the essential oil. According to several lines of evidence, the protective effects of this plant and its main constituent in different tissues including brain, heart, liver, kidney, and lung have been proved against some toxic agents either natural or chemical toxins in animal studies. In this review article, several in-vitro and animal studies in scientific databases which investigate the antidotal and protective effects of N. sativa and its main constituents against natural and chemical induced toxicities are introduced. Because human reports are rare, further studies are required to determine the efficacy of this plant as an antidote or protective agent in human intoxication. PMID:29844772

No effect of the novel antidiabetic agent nateglinide on the pharmacokinetics and anticoagulant properties of warfarin in healthy volunteers.

PubMed

Anderson, Denise M; Shelley, Sarah; Crick, Nina; Buraglio, Mauro

2002-12-01

The novel hypoglycemic agent nateglinide is pharmacologically distinct from oral hypoglycemic agents such as sulfonylureas and repaglinide. The present study investigated the effects in healthy volunteers of multiple doses of nateglinide on the pharmacokinetics and pharmacodynamics of warfarin. The study comprised a randomized two-group, two-way crossover, open-label design in 12 healthy male subjects. One group of 6 subjects initially received a single oral dose of warfarin 30 mg and then, after a 7- to 14-day washout, received both warfarin and nateglinide (120 mgnateglinide, 10 min before meals for 4 days and a single dose of 30 mg warfarin on the second day). The alternate group of 6 subjects received treatments in the opposite order. Pharmacokinetic profiles were derived from plasma warfarin and nateglinide concentrations. Prothrombin measurements were evaluated in both periods as a measure of warfarin activity. When administered alone or in combination, there were no statistically significant differences in mean warfarin (R- and S-enantiomers) or nateglinide pharmacokinetic parameters. The concurrent administration of nateglinide and warfarin did not affect the maximal change in prothrombin time that follows warfarin administration. In this study, there was no evidence of an effect of coadministration of nateglinide on the pharmacodynamic action of warfarin or any pharmacokinetic interaction between warfarin and nateglinide.

Red ginseng powder fermented with probiotics exerts antidiabetic effects in the streptozotocin-induced mouse diabetes model.

PubMed

Jang, Sun-Hee; Park, Jisang; Kim, Sae-Hae; Choi, Kyung-Min; Ko, Eun-Sil; Cha, Jeong-Dan; Lee, Young-Ran; Jang, Hyonseok; Jang, Yong-Suk

2017-12-01

Red ginseng (heat-processed Panax ginseng) is a well-known alternative medicine with pharmacological antidiabetic activity. It exerts pharmacological effects through the transformation of saponin into metabolites by the intestinal microbiota. Given that intestinal conditions and intestinal microflora vary among individuals, the pharmacological effects of orally administered red ginseng likely may vary among individuals. To overcome this variation and produce homogeneously effective red ginseng, we evaluated the antidiabetic effects of probiotic-fermented red ginseng in a mouse model. The antidiabetic efficacy of orally administered probiotic-fermented red ginseng was assessed in ICR mice after induction of diabetes using streptozotocin (170 mg/kg body weight). Samples were given orally for 8 weeks, and indicators involved in diabetic disorders such as body weight change, water intake, blood glucose, glucose tolerance and various biochemical parameters were determined. Oral administration of probiotic-fermented red ginseng significantly decreased the level of blood glucose of about 62.5% in the fasting state and induced a significant increase in glucose tolerance of about 10.2% compared to the control diabetic mice. Additionally, various indicators of diabetes and biochemical data (e.g., blood glycosylated haemoglobin level, serum concentrations of insulin, and α-amylase activity) showed a significant improvement in the diabetic conditions of the mice treated with probiotic-fermented red ginseng in comparison with those of control diabetic mice. Our results demonstrate the antidiabetic effects of probiotic-fermented red ginseng in the streptozotocin-induced mouse diabetes model and suggest that probiotic-fermented red ginseng may be a uniformly effective red ginseng product.

A Patient-level Analysis of Efficacy and Hypoglycaemia Outcomes Across Treat-to-target Trials with Insulin Glargine Added to Oral Antidiabetes Agents in People with Type 2 Diabetes

PubMed Central

DeVries, J Hans; Meneghini, Luigi; Barnett, Anthony H; Reid, Timothy; Dain, Marie-Paule; Vlajnic, Aleksandra; Traylor, Louise; Bergenstal, Richard M

2014-01-01

Abstract Background: A better understanding of hypoglycaemia risk when insulin is used in combination with one or more oral antidiabetes agents may assist in the treatment decision-making process for the clinician and address concerns regarding hypoglycaemia when initiating or intensifying insulin therapy. The objective of this study was to analyse efficacy and hypoglycaemia outcomes in people with type 2 diabetes receiving insulin glargine (IG) with metformin (MET), sulphonylurea (SU) or MET+SU. Methods: Patient-level data were pooled from 15 randomised, treat-to-target trials (fasting plasma glucose [FPG] targets <5.6 mmol/l) with a duration >24 weeks. Efficacy outcomes included glycated haemoglobin (HbA1c), FPG and HbA1c target achievement. Overall hypoglycaemia events were assessed by a confirmed PG value of <3.9, <3.1 and <2.8 mmol/l or assistance required; daytime, nocturnal (00:01-05:59 AM); and severe (assistance required or with confirmed PG <2.0 mmol/l). Results: Overall, 2,837 IG patients were analysed, with either MET (634), SU (906) or MET+SU (1,297) as background oral antidiabetes agents. Endpoint HbA1c in IG+MET and IG+MET+SU-treated patients was significantly lower than in IG+SU-treated patients (adjusted difference -0.32 %; p=0.0001 and -0.33 %; p=0.0002, respectively). Fewer patients achieved endpoint HbA1c <7.0 % with IG+SU (32 %) versus IG+MET (57 %) or IG+MET+SU (49 %). IG+SU and IG+MET+SU led to significant increases in overall, daytime and nocturnal hypoglycaemia versus IG+MET; severe hypoglycaemia was rare. Weight gain was lowest in IG+MET patients (adjusted difference -1.51 kg versus IG+SU; p<0.0001; -0.78 kg versus IG+MET+SU; p=0.0037) despite higher insulin doses (0.51 U/kg versus 0.43 and 0.42 U/kg, respectively). Conclusions: Better glycaemic goal achievement and reduced risk of hypoglycaemia and weight gain were observed with IG+MET versus IG+SU and IG+MET+SU, albeit with an increased insulin dose requirement. PMID:29872460

Update on developments with SGLT2 inhibitors in the management of type 2 diabetes.

PubMed

Nauck, Michael A

2014-01-01

The importance of the kidney's role in glucose homeostasis has gained wider understanding in recent years. Consequently, the development of a new pharmacological class of anti-diabetes agents targeting the kidney has provided new treatment options for the management of type 2 diabetes mellitus (T2DM). Sodium glucose co-transporter type 2 (SGLT2) inhibitors, such as dapagliflozin, canagliflozin, and empagliflozin, decrease renal glucose reabsorption, which results in enhanced urinary glucose excretion and subsequent reductions in plasma glucose and glycosylated hemoglobin concentrations. Modest reductions in body weight and blood pressure have also been observed following treatment with SGLT2 inhibitors. SGLT2 inhibitors appear to be generally well tolerated, and have been used safely when given as monotherapy or in combination with other oral anti-diabetes agents and insulin. The risk of hypoglycemia is low with SGLT2 inhibitors. Typical adverse events appear to be related to the presence of glucose in the urine, namely genital mycotic infection and lower urinary tract infection, and are more often observed in women than in men. Data from long-term safety studies with SGLT2 inhibitors and from head-to-head SGLT2 inhibitor comparator studies are needed to fully determine their benefit-risk profile, and to identify any differences between individual agents. However, given current safety and efficacy data, SGLT2 inhibitors may present an attractive option for T2DM patients who are failing with metformin monotherapy, especially if weight is part of the underlying treatment consideration.

Nanotechnology based approaches for anti-diabetic drugs delivery.

PubMed

Kesharwani, Prashant; Gorain, Bapi; Low, Siew Yeng; Tan, Siew Ann; Ling, Emily Chai Siaw; Lim, Yin Khai; Chin, Chuan Ming; Lee, Pei Yee; Lee, Chun Mey; Ooi, Chun Haw; Choudhury, Hira; Pandey, Manisha

2018-02-01

Nanotechnology science has been diverged its application in several fields with the advantages to operate with nanometric range of objects. Emerging field of nanotechnology has been also being approached and applied in medical biology for improved efficacy and safety. Increased success in therapeutic field has focused several approaches in the treatment of the common metabolic disorder, diabetes. The development of nanocarriers for improved delivery of different oral hypoglycemic agents compared to conventional therapies includes nanoparticles (NPs), liposomes, dendrimer, niosomes and micelles, which produces great control over the increased blood glucose level and thus becoming an eye catching and most promising technology now-a-days. Besides, embellishment of nanocarriers with several ligands makes it more targeted delivery with the protection of entrapped hypoglycaemic agents against degradation, thereby optimizing prolonged blood glucose lowering effect. Thus, nanocarriers of hypoglycemic agents provide the aim towards improved diabetes management with minimized risk of acute and chronic complications. In this review, we provide an overview on distinctive features of each nano-based drug delivery system for diabetic treatment and current NPs applications in diabetes management. Copyright © 2017 Elsevier B.V. All rights reserved.

Insulinotrophic and insulin-like effects of a high molecular weight aqueous extract of Pterocarpus marsupium Roxb. hardwood.

PubMed

Mohankumar, Suresh K; O'Shea, Tim; McFarlane, James R

2012-05-07

Pterocarpus marsupium Roxb. (PM) is an Ayurvedic traditional medicine well known for its antidiabetic potential. To fractionate the antidiabetic constituent(s) of the aqueous of extract of PM hardwood (PME). Bio-assay methods including, insulin secretion from mouse pancreas and glucose uptake by mouse skeletal muscle, were used to determine and fractionate the antidiabetic activity of PME. Results obtained from the in vitro experiments were then verified by examining the effect of PME on glucose clearance in normoglycemic, non-diabetic sheep in vivo. Exposure of mouse pancreatic and muscle tissues to PME stimulated the insulin secretion and glucose uptake, respectively, in a concentration-dependent manner. PME-mediated muscle glucose uptake was not potentiated in the presence of insulin indicating that PME acts via pathways which are utilized by insulin. Bio-assay-guided fractionation of PME yielded a high molecular weight fraction which had potent antidiabetic properties in vitro, and in in vivo. Our findings, we believe for the first time, provide novel insights for the antidiabetic constituents of PM and demonstrate that a high molecular weight constituent(s) of PM has potent insulinotrophic and insulin-like properties. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Characterization, antibacterial, antioxidant, antidiabetic, anti-inflammatory and antityrosinase activity of green synthesized silver nanoparticles using Calophyllum tomentosum leaves extract

NASA Astrophysics Data System (ADS)

Govindappa, M.; Hemashekhar, B.; Arthikala, Manoj-Kumar; Ravishankar Rai, V.; Ramachandra, Y. L.

2018-06-01

The current research study is to develop an easy and eco-friendly method for the synthesis of AgNPs using aqueous leaf extract of Calophyllum tomentosum (CtAgNPs) and evaluated the extract to know the effects of anti-bacterial, antioxidant, anti-diabetic, anti-inflammatory and anti-tyrosinase activity. Using UV-vis spectrophotometer, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX) characterized the Calophyllum tomentosum mediated silver nanoparticles. The leaf extract of C. tomentosum yielded flavonoids, saponins, tannins, alkaloids, glycosides, phenols, terpenoids and coumarins. AgNPs formation was confirmed by UV-vis spectra at 438 nm. Crystalline structure with a face centered cubic (fcc) of AgNPs was observed in XRD. FTIR had shown that the phytochemicals were responsible for the reduction and capping material of silver nanoparticles. The size and shape of the AgNPs were determined using SEM. From EDX study analysed the strong absorption property of AgNPs. The CtAgNPs have showed significant antibacterial activity on multi drug resistance bacteria. The CtAgNPs had shown strong antioxidant (DPPH, H2O2 scavenging, nitric oxide scavenging power, reducing power) activities. The CtAgNPs had strongly inhibited the α-glucosidase and DPPIV compared to α-amylase. The CtAgNPs exhibited strong anti-inflammatory activity (albumin denaturation, membrane stabilization, heat haemolytic, protein inhibitory, lipoxygenase, xanthine oxidase) and tyrosinase inhibitory activity. To our best knowledge, this is the first attempt on the synthesis of silver nanoparticles using Calophyllum tomentosum leaves extract. Hence, to validate our results the in vivo studies at molecular level are needed to develop an antioxidant, anti-diabetic and anti-inflammatory agent.

Gedunin and Azadiradione: Human Pancreatic Alpha-Amylase Inhibiting Limonoids from Neem (Azadirachta indica) as Anti-Diabetic Agents.

PubMed

Ponnusamy, Sudha; Haldar, Saikat; Mulani, Fayaj; Zinjarde, Smita; Thulasiram, Hirekodathakallu; RaviKumar, Ameeta

2015-01-01

Human pancreatic α-amylase (HPA) inhibitors offer an effective strategy to lower postprandial hyperglycemia via control of starch breakdown. Limonoids from Azadirachta indica known for their therapeutic potential were screened for pancreatic α-amylase inhibition, a known anti-diabetic target. Studies were carried out to reveal their mode of action so as to justify their hypoglycemic potential. Of the nine limonoids isolated/semi-synthesized from A.indica and screened for α-amylase inhibition, azadiradione and exhibited potential inhibition with an IC50 value of 74.17 and 68.38 μM, respectively against HPA under in vitro conditions. Further screening on AR42J α-amylase secretory cell line for cytotoxicity and bioactivity revealed that azadiradione and gedunin exhibited cytotoxicity with IC50 of 11.1 and 13.4μM. Maximal secreted α-amylase inhibition of 41.8% and 53.4% was seen at 3.5 and 3.3μM, respectively. Michaelis-Menten kinetics suggested a mixed mode of inhibition with maltopentaose (Ki 42.2, 18.6 μM) and starch (Ki' 75.8, 37.4 μM) as substrate with a stiochiometry of 1:1 for both azadiradione and gedunin, respectively. The molecular docking simulation indicated plausible π-alkyl and alkyl-alkyl interactions between the aromatic amino acids and inhibitors. Fluorescence and CD confirmed the involvement of tryptophan and tyrosine in ligand binding to HPA. Thermodynamic parameters suggested that binding is enthalpically and entropically driven with ΔG° of -21.25 kJ mol-1 and -21.16 kJ mol-1 for azadiradione and gedunin, respectively. Thus, the limonoids azadiradione and gedunin could bind and inactivate HPA (anti-diabetic target) and may prove to be lead drug candidates to reduce/control post-prandial hyperglycemia.

Marine pharmacology in 2001–2002: Marine compounds with anthelmintic, antibacterial, anticoagulant, antidiabetic, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems and other miscellaneous mechanisms of action

PubMed Central

Mayer, Alejandro M.S.; Hamann, Mark T.

2016-01-01

During 2001–2002, research on the pharmacology of marine chemicals continued to be global in nature involving investigators from Argentina, Australia, Brazil, Canada, China, Denmark, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Pakistan, the Philippines, Russia, Singapore, Slovenia, South Africa, South Korea, Spain, Sweden, Switzerland, Thailand, United Kingdom, and the United States. This current article, a sequel to the authors’ 1998, 1999 and 2000 marine pharmacology reviews, classifies 106 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria, on the basis of peer-reviewed preclinical pharmacology. Anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 56 marine chemicals. An additional 19 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as to possess anti-inflammatory and antidiabetic effects. Finally, 31 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2001–2002 pharmacological research with marine chemicals continued to contribute potentially novel chemical leads for the ongoing global search for therapeutic agents for the treatment of multiple disease categories. PMID:15919242

Effect of Yeonryeonggobon-dan (YRGBD), an herbal complex, on glycemic control in patients with Type 2 diabetes mellitus: a case series.

PubMed

Kim, Jiman; Byun, A Ri; Kwon, Seungwon

2014-12-01

Diabetes mellitus has significant effects on the human body. Recently, herbal medicines have received attention as complementary anti-diabetic agents on the basis of the results of several experimental studies. We present a series of 38 cases that demonstrate the positive effect of Yeonryeonggobon-dan (YRGBD), an herbal complex, in lowering blood sugar levels in patients with uncontrolled type 2 diabetes mellitus. We reviewed the medical records of 38 patients treated with YRGBD. The types and doses of other hypoglycemic agents administered to the patients remained unchanged during treatment with YRGBD. After YRGBD therapy, the glycated haemoglobin level decreased from 76.16±19.90mmol/mol (9.11±1.82%) to 51.21±8.82mmol/mol (6.84±0.81%). There was a statistically significant difference between the glycated haemoglobin levels measured before and after treatment (paired t test, p<0.001). In the present study, we show the clinical effects of YRGBD on blood sugar control in patients with type 2 diabetes mellitus. Further clinical studies investigating the effects of YRGBD are needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antidiabetic Effects of Tea.

PubMed

Fu, Qiu-Yue; Li, Qing-Sheng; Lin, Xiao-Ming; Qiao, Ru-Ying; Yang, Rui; Li, Xu-Min; Dong, Zhan-Bo; Xiang, Li-Ping; Zheng, Xin-Qiang; Lu, Jian-Liang; Yuan, Cong-Bo; Ye, Jian-Hui; Liang, Yue-Rong

2017-05-20

Diabetes mellitus (DM) is a chronic endocrine disease resulted from insulin secretory defect or insulin resistance and it is a leading cause of death around the world. The care of DM patients consumes a huge budget due to the high frequency of consultations and long hospitalizations, making DM a serious threat to both human health and global economies. Tea contains abundant polyphenols and caffeine which showed antidiabetic activity, so the development of antidiabetic medications from tea and its extracts is increasingly receiving attention. However, the results claiming an association between tea consumption and reduced DM risk are inconsistent. The advances in the epidemiologic evidence and the underlying antidiabetic mechanisms of tea are reviewed in this paper. The inconsistent results and the possible causes behind them are also discussed.

Synthesis, spectroscopic, structural and thermal characterizations of vanadyl(IV) adenine complex prospective as antidiabetic drug agent

NASA Astrophysics Data System (ADS)

El-Megharbel, Samy M.; Hamza, Reham Z.; Refat, Moamen S.

2015-01-01

The vanadyl(IV) adenine complex; [VO(Adn)2]ṡSO4; was synthesized and characterized. The molar conductivity of this complex was measured in DMSO solution that showed an electrolyte nature. Spectroscopic investigation of the green solid complex studied here indicate that the adenine acts as a bidentate ligand, coordinated to vanadyl(IV) ions through the nitrogen atoms N7 and nitrogen atom of amino group. Thus, from the results presented the vanadyl(IV) complex has square pyramid geometry. Further characterizations using thermal analyses and scanning electron techniques was useful. The aim of this paper was to introduce a new drug model for the diabetic complications by synthesized a novel mononuclear vanadyl(IV) adenine complex to mimic insulin action and reducing blood sugar level. The antidiabetic ability of this complex was investigated in STZ-induced diabetic mice. The results suggested that VO(IV)/adenine complex has antidiabetic activity, it improved the lipid profile, it improved liver and kidney functions, also it ameliorated insulin hormone and blood glucose levels. The vanadyl(IV) complex possesses an antioxidant activity and this was clear through studying SOD, CAT, MDA, GSH and methionine synthase. The current results support the therapeutic potentiality of vanadyl(IV)/adenine complex for the management and treatment of diabetes.

The Hypoglycemic, Hypolipidemic, and Anti-Diabetic Nephritic Activities of Zeaxanthin in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats.

PubMed

Kou, Ling; Du, Mingzhao; Zhang, Chaopu; Dai, Zhiyin; Li, Xuan; Zhang, Baohai

2017-07-01

Zeaxanthin (ZA), an important compound found in Lycium barbarum, shows various pharmacodynamic effects. In our present study, a high-fat, high-sucrose diet and streptozotocin (STZ)-induced diabetic rat model was used to investigate the antidiabetic activities of ZA. After a 4-week administration of 200 and 400 mg/kg of ZA and 100 mg/kg of metformin hydrochloride, various blood biochemical indexes were detected. ZA strongly normalized the reduced bodyweight and enhanced fasting blood glucose in diabetic rats. The positive data obtained from the oral glucose tolerance test further confirmed its antidiabetic effects. ZA displayed significant hypolipidemic activities indicated by its modulation of serum levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. The antidiabetic nephropathy of ZA was confirmed by its regulation of pathological kidney structures, urine levels of n-acetyl-β-d-glucosaminidase and albuminuria, and serum levels of urea nitrogen. ZA inhibited the serum levels of inflammatory factors including interleukin-2 (IL-2), IL-6, tumor necrosis factor-α, and nuclear factor kappa B, further confirming its renal protection. Moreover, the serum imbalances in superoxide dismutase, glutathione peroxidase, methane dicarboxylic aldehyde, and catalase were normalized by ZA, suggesting its antioxidant properties. Altogether, ZA produced hypoglycemic, hypolipidemic, and antidiabetic nephritic effects in a diet-STZ-induced diabetic rat model.

Antidiabetic effects of Momordica charantia (bitter melon) and its medicinal potency

PubMed Central

Joseph, Baby; Jini, D

2013-01-01

Diabetes mellitus is among the most common disorder in developed and developing countries, and the disease is increasing rapidly in most parts of the world. It has been estimated that up to one-third of patients with diabetes mellitus use some form of complementary and alternative medicine. One plant that has received the most attention for its anti-diabetic properties is bitter melon, Momordica charantia (M. charantia), commonly referred to as bitter gourd, karela and balsam pear. Its fruit is also used for the treatment of diabetes and related conditions amongst the indigenous populations of Asia, South America, India and East Africa. Abundant pre-clinical studies have documented in the anti-diabetic and hypoglycaemic effects of M. charantia through various postulated mechanisms. However, clinical trial data with human subjects are limited and flawed by poor study design and low statistical power. The present review is an attempt to highlight the antidiabetic activity as well as phytochemical and pharmacological reports on M. charantia and calls for better-designed clinical trials to further elucidate its possible therapeutic effects on diabetes.

Anti-diabetic effects of the ethanol extract of a functional formula diet in mice fed with a fructose/fat-rich combination diet.

PubMed

Cheng, Qian; Zhang, Xiaofeng; Wang, Ou; Liu, Jia; Cai, Shengbao; Wang, Ruojun; Zhou, Feng; Ji, Baoping

2015-01-01

Rhizoma dioscorea, Lycium barbarum, Prunella vulgaris and hawthorn are well known in both traditional food and folk medicine. Each of these plants reportedly possesses beneficial effects in the treatment of diabetes. In this study an anti-diabetic health-promoting diet was formulated by mixing the herbs in a ratio of 6:4:2:3, and the anti-diabetic effect and underlying mechanism were elucidated in vivo. Compared with the model control group, the formula, especially its ethanol extract (EF), could improve glucose intolerance and normalize the lipid profile. The mechanisms responsible for the amelioration of glucose and lipid metabolism in mice were an increase in peripheral and hepatic insulin sensitivity, a decrease in serum free fatty acid level, enhanced hepatic glucokinase activity and glycogen content and improved serum antioxidant activity. Hepatic histopathological examination also showed that EF administration markedly decreased fatty deposits in the liver of mice. The results of the present study demonstrated that the prepared functional formula diet is a potent alternative as an anti-diabetic health-promoting diet. © 2014 Society of Chemical Industry.

New directions in type 2 diabetes mellitus: an update of current oral antidiabetic therapy.

PubMed Central

Brown, D. L.; Brillon, D.

1999-01-01

This article reviewed the relevant literature including published clinical trials and reviews on currently available oral hypoglycemic agents. Results showed that the benefits of glycemic control have been established through multiple clinical trials. Long-term control of blood glucose levels in type 1 and type 2 diabetic patients will decrease the incidence and prolong the time until progression of diabetic retinopathy, nephropathy, and neuropathy. Our increased understanding of the pathophysiology behind type 2 diabetes has led to the development of many new agents that are aimed at treating the underlying insulin resistance and relative insulinopenia. The sulfonylureas as a group have been used for many years and act by stimulating insulin secretion. They are useful alone or as combination therapy with insulin or another oral hypoglycemic agent. The biguanides act by decreasing hepatic glucose production and by increasing peripheral insulin sensitivity. The alpha-glucosidase inhibitors act nonsystemically by blocking the metabolism of digested polysaccharides and therefore lowering the amount of carbohydrate absorbed in a meal. Benzoic acid derivatives act in a manner similar to that of sulfonylureas by enhancing pancreatic insulin production. They offer a shorter duration of action, lowering the risk of hypoglycemia. The thiazolidinediones increase peripheral insulin sensitivity and are effective as both monotherapy and combination therapy. Oral hypoglycemic agents, when properly administered, are very effective in controlling type 2 diabetes and preventing long-term complications. PMID:10643211

Analysis of glycation induced protein cross-linking inhibitory effects of some antidiabetic plants and spices.

PubMed

Perera, Handunge Kumudu Irani; Handuwalage, Charith Sandaruwan

2015-06-09

Protein cross-linking which occurs towards the latter part of protein glycation is implicated in the development of chronic diabetic complications. Glycation induced protein cross-linking inhibitory effects of nine antidiabetic plants and three spices were evaluated in this study using a novel, simple, electrophoresis based method. Methanol extracts of thirteen plants including nine antidiabetic plants and three spices were used. Lysozyme and fructose were incubated at 37 °C in the presence or absence of different concentrations of plant extracts up to 31 days. Standard glycation inhibitor aminoguanidine and other appropriate controls were included. A recently established sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE) method was used to detect the products of protein cross-linking in the incubation mixtures. High molecular weight protein products representing the dimer, trimer and tetramer of lysozyme were detected in the presence of fructose. Among the nine antidiabetic plants, seven showed glycation induced protein cross-linking inhibitory effects namely Ficus racemosa (FR) stem bark, Gymnema sylvestre (GS) leaves, Musa paradisiaca (MP) yam, Phyllanthus debilis (PD) whole plant, Phyllanthus emblica (PE) fruit, Pterocarpus marsupium (PM) latex and Tinospora cordifolia (TC) leaves. Inhibition observed with Coccinia grandis (CG) leaves and Strychnos potatorum (SP) seeds were much low. Leaves of Gymnema lactiferum (GL), the plant without known antidiabetic effects showed the lowest inhibition. All three spices namely Coriandrum sativum (CS) seeds, Cinnamomum zeylanicum (CZ) bark and Syzygium aromaticum (SA) flower buds showed cross-link inhibitory effects with higher effects in CS and SA. PD, PE, PM, CS and SA showed almost complete inhibition on the formation of cross-linking with 25 μg/ml extracts. Methanol extracts of PD, PE, PM, CS and SA have shown promising inhibitory effects on glycation induced protein cross-linking.

Antidiabetic effects of extracts from Psidium guajava.

PubMed

Oh, Won Keun; Lee, Chul Ho; Lee, Myung Sun; Bae, Eun Young; Sohn, Cheon Bae; Oh, Hyuncheol; Kim, Bo Yeon; Ahn, Jong Seog

2005-01-15

During a screening of medicinal plants for inhibition of protein tyrosine phosphatase1B (PTP1B), an extract from Psidium guajava (Myrtaceae) leaves exhibited significant inhibitory effect on PTP1B. Thus, its antidiabetic effect on Lepr(db)/Lepr(db) mice was evaluated. Significant blood glucose lowering effects of the extract were observed after intraperitoneal injection of the extract at a dose of 10mg/kg in both 1- and 3-month-old Lepr(db)/Lepr(db) mice. In addition, histological analysis of the liver from the butanol-soluble fraction treated Lepr(db)/Lepr(db) mice revealed a significant decrease in the number of lipid droplets compared to the control mice. Taken together, it was suggested that the extract from Psidium guajava leaves possesses antidiabetic effect in type 2 diabetic mice model and these effect is, at least in part, mediated via the inhibition of PTP1B.

A Common Susceptibility Gene for Type 2 Diabetes Is Associated with Drug Response to a DPP-4 Inhibitor: Pharmacogenomic Cohort in Okinawa Japan.

PubMed

Osada, Uru Nezu; Sunagawa, Hiroshi; Terauchi, Yasuo; Ueda, Shinichiro

2016-01-01

We investigated the association between common type 2 susceptibility variants of CDK5 regulatory subunit associated protein 1-like 1(CDKAL1) and therapeutic responses to anti-diabetic agents among patients with type 2 diabetes. Two SNPs (rs7754840: C>G, rs7756992: A>G) were genotyped via the Taqman PCR method. A total of 798 type 2 diabetic patients were included. HbA1c reduction after use of DPP-4 inhibitors for 3 months was significantly greater in patients with a risk allele for type 2 diabetes (GG -0.4%, CG -0.5%, CC -0.8%, p = 0.02 for rs7754840 and AA -0.4%, AG -0.5%, GG -0.8%, p = 0.01 for rs7756992). Linear regression analysis showed that per allele reductions of hemoglobin A1c (HbA1c) after 3 months were -0.10% for rs7754840 (p = 0.02) and -0.13% for rs7756992 (p = 0.0008) after adjusting for clinically influential covariates such as age, sex, BMI, duration of diabetes, baseline HbA1c and concomitant anti-diabetic agents. The results suggested that common variants of CDKAL1 are associated with therapeutic response to DPP-4 inhibitors.

Medicinal agents in the metabolic syndrome.

PubMed

Baños, G; Pérez-Torres, I; El Hafidi, M

2008-10-01

The metabolic syndrome (MS) has become a worldwide health problem. It is difficult for patients to follow a diet/exercise regime that would improve their symptoms, therefore the investigation of agents that may deal with its more serious aspects is an important medical field for research. The cardiovascular consequences associated with the syndrome and some of the therapeutic approaches are discussed. The different agents can be divided into several groups: Inorganic/ organic: Zinc complexes with garlic components as insulino-mimetics; Selenium as antioxidant; Copper, Zinc and Manganese as microcomponents of antioxidant enzymes. Organic: Natural or Synthetic: Glycine is effective in lowering blood pressure, TBARS, intra-abdominal fat tissue and triglycerides in sucrose-fed rats. Pharmaceutical products: Fibrates, Lipid-lowering drugs. Antidiabetics. Anti-gout agents. On the other hand there are natural products such as those of animal origin: Sex hormones (also synthetic) used in the problems of menopause and hypoandrogenism frequently found in the MS, antioxidant Omega-3-oils (fish oils) or Vegetal: for example Digitalis pupurea, century-old cardiovascular medication as well as Magnolia officinalis; Spirulina maxima with beneficial effects as antioxidant and lipid-lowering agent, among others. Prickly Pear Cacti. (Opuntia Ficus- Indica Cochlospermum vitifolium (Willd.) Spreng) whose many properties against diabetes and hypercholesterolemia have been empirically known for many years. Perezone (from Perezia plants, a.k.a. Peonia) described as an antiplatelet aggregating agent. The mixed elements in the Mediterranean diet: Fish, salads (peppers, tomatoes), olive oil, garlic, red wine which combines fish oils, garlic and avocado as well as antioxidants from the rest of its components.

Anti-Diabetic, Anti-Oxidant and Anti-Hyperlipidemic Activities of Flavonoids from Corn Silk on STZ-Induced Diabetic Mice.

PubMed

Zhang, Yan; Wu, Liying; Ma, Zhongsu; Cheng, Jia; Liu, Jingbo

2015-12-23

Corn silk is a well-known ingredient frequently used in traditional Chinese herbal medicines. This study was designed to evaluate the anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of crude flavonoids extracted from corn silk (CSFs) on streptozotocin (STZ)-induced diabetic mice. The results revealed that treatment with 300 mg/kg or 500 mg/kg of CSFs significantly reduced the body weight loss, water consumption, and especially the blood glucose (BG) concentration of diabetic mice, which indicated their potential anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the anti-oxidant effects. Besides, several serum lipid values including total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C) were reduced and the high density lipoprotein cholesterol level (HDL-C) was increased. The anti-diabetic, anti-oxidant and anti-hyperlipidemic effect of the CSFs suggest a potential therapeutic treatment for diabetic conditions.

Insulin use increases risk of asthma but metformin use reduces the risk in patients with diabetes in a Taiwanese population cohort.

PubMed

Chen, Chiung-Zuei; Hsu, Chih-Hui; Li, Chung-Yi; Hsiue, Tzuen-Ren

2017-12-01

Recent reports have suggested that insulin promotes airway smooth muscle contraction and enhances airway hyperresponsiveness, which are cardinal features of asthma. In contrast, metformin can reduce both airway inflammatory and remodeling properties. However, these results are all from in vitro and animal studies. This study investigated whether diabetes and various antidiabetic agents associate with the risk of asthma. We used a retrospective population-based cohort study using Taiwan's National Health Insurance claim database from 2000 to 2010 and a Cox proportional hazards regression model to compare the incidence of asthma between patients with diabetes (n = 19,428) and a matched non-diabetic group (n = 38,856). We also used a case-control study nested from the above cohort including 1,982 incident cases of asthma and 1,982 age- and sex-matched controls. A time density sampling technique was used to assess the effects of various antidiabetic agents on the risk of asthma. The incidence of asthma was significantly higher in the diabetic cohort than that in the non-diabetic cohort after adjustment for age, sex, and obesity, with a hazard ratio of 1.30 (95% confidence interval [CI]: 1.24-1.38). Insulin was found to increase the risk of asthma among diabetic patients (odds ratio [OR] 2.23; 95% CI: 1.52-3.58). In contrast, the use of metformin correlated with a decreased risk of asthma (OR 0.75; 95% CI: 0.60-0.95). Individuals with diabetes are at an increased risk of asthma. Insulin may further increase the risk of asthma, but the risk could possibly be reduced by using metformin.

Optimizing insulin secretagogue therapy in patients with type 2 diabetes: a randomized double-blind study with repaglinide.

PubMed

Schmitz, Ole; Lund, Sten; Andersen, Per Heden; Jønler, Morten; Pørksen, Nils

2002-02-01

Repaglinide, a novel antidiabetic agent that has a rapid onset and short duration of action, was developed for mealtime dosing. The purpose of this pharmacodynamic study was to validate a prandial regimen of repaglinide by comparing meal-related dosing with a regimen in which the same total daily dose was divided into only two doses at morning and evening meals. The study was a double-blind, randomized, parallel-group trial in 19 antidiabetic agent-naive subjects with type 2 diabetes (mean age 58 years, known duration of diabetes 3.5 years, HbA(1c) 7.3%, and BMI 32 kg/m(2)). Patients were randomly assigned to receive repaglinide either before each of the three main meals or before breakfast and before the evening meal. Patients in both groups received the same total daily dose of repaglinide. Twenty-four hour profiles of blood glucose, plasma insulin, and plasma C-peptide concentrations were measured at baseline and after 4 weeks of treatment. Repaglinide increased postprandial insulin levels and markedly reduced postprandial glucose levels relative to baseline in both groups. Significant reductions were also recorded in fasting blood glucose and HbA(1c) levels. The repaglinide regimen, in which a dose was taken before each main meal, was more effective in improving glycemic control (including postprandial glucose and HbA(1c) levels) than the same total dose of repaglinide divided into morning and evening mealtime doses. These data support the strategy of mealtime dosing with repaglinide. The improvements in glycemic control observed in these patients are encouraging. In addition to classic parameters of glycemic control, improvements in postprandial glucose excursions may prove to be important because postprandial hyperglycemia has been suggested to be an independent risk factor for cardiovascular disease in diabetes.

Antifungal activity of Momordica charantia seed extracts toward the pathogenic fungus Fusarium solani L.

PubMed

Wang, Shuzhen; Zheng, Yongliang; Xiang, Fu; Li, Shiming; Yang, Guliang

2016-10-01

Momordica charantia L., a vegetable crop with high nutritional value, has been used as an antimutagenic, antihelminthic, anticancer, antifertility, and antidiabetic agent in traditional folk medicine. In this study, the antifungal activity of M. charantia seed extract toward Fusarium solani L. was evaluated. Results showed that M. charantia seed extract effectively inhibited the mycelial growth of F. solani, with a 50% inhibitory rate (IC 50 ) value of 108.934 μg/mL. Further analysis with optical microscopy and fluorescence microscopy revealed that the seed extract led to deformation of cells with irregular budding, loss of integrity of cell wall, as well as disruption of the fungal cell membrane. In addition, genomic DNA was also severely affected, as small DNA fragments shorter than 50 bp appeared on agarose gel. These findings implied that M. charantia seed extract containing α-momorcharin, a typical ribosome-inactivating protein, could be an effective agent in the control of fungal pathogens, and such natural products would represent a sustainable alternative to the use of synthetic fungicides. Copyright © 2016. Published by Elsevier B.V.

Microencapsulation Approach for Orally Extended Delivery of Glipizide: In vitro and in vivo Evaluation

PubMed Central

Abdelbary, A.; El-gendy, N. A.; Hosny, A.

2012-01-01

Glipizide is an effective antidiabetic agent, however, it suffers from relatively short biological half-life. To solve this encumbrance, it is a prospective candidate for fabricating glipizide extended release microcapsules. Microencapsulation of glipizde with a coat of alginate alone or in combination with chitosan or carbomer 934P was prepared employing ionotropic gelation process. The prepared microcapsules were evaluated in vitro by microscopical examination, determination of the particle size, yield and microencapsulation efficiency. The filled capsules were assessed for content uniformity and drug release characteristics. Stability study of the optimised formulas was carried out at three different temperatures over 12 weeks. In vivo bioavailability study and hypoglycemic activity of C9 microcapsules were done on albino rabbits. All formulas achieved high yield, microencapsulation efficiency and extended t1/2. C9 and C19 microcapsules attained the most optimised results in all tests and complied with the dissolution requirements for extended release dosage forms. These two formulas were selected for stability studies. C9 exhibited longer shelf-life and hence was chosen for in vivo studies. C9 microcapsules showed an improvement in the drug bioavailability and significant hypoglycemic activity compared to immediate release tablets (Minidiab® 5 mg). The optimised microcapsule formulation developed was found to produce extended antidiabetic activity. PMID:23626387

Identification of a novel selective PPARγ ligand with a unique binding mode and improved therapeutic profile in vitro

PubMed Central

Yi, Wei; Shi, Jingjing; Zhao, Guanguan; Zhou, X. Edward; Suino-Powell, Kelly; Melcher, Karsten; Xu, H. Eric

2017-01-01

Thiazolidinediones (TZD) function as potent anti-diabetic drugs through their direct action on the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), but their therapeutic benefits are compromised by severe side effects. To address this concern, here we developed a potent “hit” compound, VSP-51, which is a novel selective PPARγ-modulating ligand with improved therapeutic profiles in vitro compared to the multi-billion dollar TZD drug rosiglitazone (Rosi). Unlike Rosi, VSP-51 is a partial agonist of PPARγ with improved insulin sensitivity due to its ability to bind PPARγ with high affinity without stimulating adipocyte differentiation and the expression of adipogenesis-related genes. We have determined the crystal structure of the PPARγ ligand-binding domain (LBD) in complex with VSP-51, which revealed a unique mode of binding for VSP-51 and provides the molecular basis for the discrimination between VSP-51 from TZDs and other ligands such as telmisartan, SR1663 and SR1664. Taken together, our findings demonstrate that: a) VSP-51 can serve as a promising candidate for anti-diabetic drug discovery; and b) provide a rational basis for the development of future pharmacological agents targeting PPARγ with advantages over current TZD drugs. PMID:28128331

Add-on treatment with teneligliptin ameliorates glucose fluctuations and improves glycemic control index in Japanese patients with type 2 diabetes on insulin therapy.

PubMed

Tanaka, Seiichi; Suzuki, Kunihiro; Aoki, Chie; Niitani, Mai; Kato, Kanako; Tomotsune, Takanori; Aso, Yoshimasa

2014-12-01

This study investigated whether teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, ameliorated glucose fluctuations in hospitalized Japanese patients with type 2 diabetes receiving insulin therapy, with or without other antidiabetes drugs, and using continuous glucose monitoring (CGM). Twenty-six patients with type 2 diabetes were admitted for glycemic control. After admission, patients continued to be treated with optimal dietary therapy plus insulin therapy, with or without other antidiabetes drugs, until they achieved stable glycemic control. CGM measurements were made for 7 consecutive days. On Days 1-3, patients received insulin with or without other antidiabetes drugs, and on Days 4-7, teneligliptin 20 mg once daily at breakfast was added to ongoing therapy. Doses of insulin were fixed during the study. Levels of serum glycated albumin (GA), 1,5-anhydro-d-glucitol (1,5-AG), and high-sensitivity C-reactive protein (hsCRP) were measured. Add-on treatment with teneligliptin led to significant improvements in 24-h mean glucose levels, the proportion of time in normoglycemia, mean amplitude of glycemic excursions, and total area under the curve within 2 h after each meal. The proportion of time in hypoglycemia and hsCRP levels did not increase significantly compared with before teneligliptin. Values of 1,5-AG and GA were significantly improved by treatment with teneligliptin. Addition of teneligliptin to insulin therapy led to a significant improvement in diurnal glycemic control and significant reductions in glucose fluctuations in 24-h periods without increasing hypoglycemia in Japanese patients with type 2 diabetes on insulin therapy, with or without other antidiabetes agents.

Antidiabetic and antihiperlipidemic effect of Andrographis paniculata (Burm. f.) Nees and andrographolide in high-fructose-fat-fed rats

PubMed Central

Nugroho, Agung Endro; Andrie, Mohamad; Warditiani, Ni Kadek; Siswanto, Eka; Pramono, Suwidjiyo; Lukitaningsih, Endang

2012-01-01

Objectives: Andrographis paniculata (Burm. f.) Nees originates from India and grows widely in many areas in Southeast Asian countries. Andrographis paniculata (Burm. f.) Nees has shown an antidiabetic effect in type 1 DM rats. The present study investigates the purified extract of the plant and its active compound andrographolide for antidiabetic and antihyperlipidemic effects in high-fructose-fat-fed rats, a model of type 2 DM rats. Materials and Methods: Hyperglycemia in rats was induced by high-fructose-fat diet containing 36% fructose, 15% lard, and 5% egg yolks in 0.36 g/200 gb.wt. 55 days. The rats were treated with the extract or test compound on the 50th day. Antidiabetic activity was measured by estimating mainly the pre– and postprandial blood glucose levels and other parameters such as cholesterol, LDL, triglyceride, and body weight. Results: The purified extract and andrographolide significantly (P<0.05) decreased the levels of blood glucose, triglyceride, and LDL compared to controls. However, no changes were observed in serum cholesterol and rat body weight. Metformin also showed similar effects on these parameters. Conclusions: Andrographis paniculata (Burm. f.) Nees or its active compound andrographolide showed hypoglycemic and hypolipidemic effects in high-fat-fructose-fed rat. PMID:22701250

Update on developments with SGLT2 inhibitors in the management of type 2 diabetes

PubMed Central

Nauck, Michael A

2014-01-01

The importance of the kidney’s role in glucose homeostasis has gained wider understanding in recent years. Consequently, the development of a new pharmacological class of anti-diabetes agents targeting the kidney has provided new treatment options for the management of type 2 diabetes mellitus (T2DM). Sodium glucose co-transporter type 2 (SGLT2) inhibitors, such as dapagliflozin, canagliflozin, and empagliflozin, decrease renal glucose reabsorption, which results in enhanced urinary glucose excretion and subsequent reductions in plasma glucose and glycosylated hemoglobin concentrations. Modest reductions in body weight and blood pressure have also been observed following treatment with SGLT2 inhibitors. SGLT2 inhibitors appear to be generally well tolerated, and have been used safely when given as monotherapy or in combination with other oral anti-diabetes agents and insulin. The risk of hypoglycemia is low with SGLT2 inhibitors. Typical adverse events appear to be related to the presence of glucose in the urine, namely genital mycotic infection and lower urinary tract infection, and are more often observed in women than in men. Data from long-term safety studies with SGLT2 inhibitors and from head-to-head SGLT2 inhibitor comparator studies are needed to fully determine their benefit–risk profile, and to identify any differences between individual agents. However, given current safety and efficacy data, SGLT2 inhibitors may present an attractive option for T2DM patients who are failing with metformin monotherapy, especially if weight is part of the underlying treatment consideration. PMID:25246775

Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice.

PubMed

Tian, Cai-Ming; Jiang, Xin; Ouyang, Xiao-Xi; Zhang, Ya-Ou; Xie, Wei-Dong

2016-07-01

The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin (BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase (pAMPK) expression and decreased tumor necrosis factor alpha (TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of pAMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

A study on ethosomes as mode for transdermal delivery of an antidiabetic drug.

PubMed

Bodade, Siddhodhan S; Shaikh, Karimunnisa Sameer; Kamble, Meghana S; Chaudhari, Praveen D

2013-01-01

A transdermal delivery system is warranted for repaglinide (RPG) which possesses half-life of 1 h and oral bioavailability of 56%. Ethosomes are useful tools for transdermal drug delivery. To prepare and evaluate ethosomes as mode for transdermal delivery of RPG. Ethosomes loaded with RPG were prepared from dipalmitoyl phosphatidylcholine and ethanol by the cold method. They were characterized using Fourier transform infrared spectroscopy and differential scanning calorimetry. They were evaluated for vesicle size, entrapment efficiency and ex-vivo skin permeation. Ethosomal composition was optimized using the 3(2) factorial design. Gel containing optimzsed ethosomes was studied for antidiabetic activity in rats. RPG ethosomes possessing the size of 0.171-1.727 µm and entrapment efficiency of 75-92% were obtained. They demonstrated a significantly higher permeation (64-97% of the administered dose) across excised rat skin when compared to free drug and its hydro alcoholic solution. In-vivo, RPG ethosomal system caused sustained antidiabetic effect. The lipid and ethanol concentration affected the physicochemical attributes and performance of ethosomes. The flexible ethosomes permeated the stratum corneum and improvized the availability of RPG for antidiabetic action. They prolonged the antidiabetic effect of RPG over a significantly longer period of time in comparison with the equivalent oral dose. Ethosomal system can successfully deliver RPG transdermally; sustain its effect and thus reduce its dosing frequency. Ethosomes are useful for enhancing the efficacy of RPG in the treatment of diabetes.

Repaglinide: a review of its therapeutic use in type 2 diabetes mellitus.

PubMed

Culy, C R; Jarvis, B

2001-01-01

Repaglinide, a carbamoylmethyl benzoic acid derivative, is the first of a new class of oral antidiabetic agents designed to normalise postprandial glucose excursions in patients with type 2 diabetes mellitus. Like the sulphonylureas, repaglinide reduces blood glucose by stimulating insulin release from pancreatic beta-cells, but differs from these and other antidiabetic agents in its structure, binding profile, duration of action and mode of excretion. In clinical trials of up to 1-year's duration, repaglinide maintained or improved glycaemic control in patients with type 2 diabetes mellitus. In comparative, 1-year, double-blind, randomised trials (n = 256 to 544), patients receiving repaglinide (0.5 to 4mg before 3 daily meals) achieved similar glycaemic control to that in patients receiving glibenclamide (glyburide) < or = 15 mg/day and greater control than patients receiving glipizide < or = 15 mg/day. Changes from baseline in glycosylated haemoglobin and fasting blood glucose levels were similar between patients receiving repaglinide and glibenclamide in all studies; however, repaglinide was slightly better than glibenclamide in reducing postprandial blood glucose in I short term study (n = 192). Patients can vary their meal timetable with repaglinide: the glucose-lowering efficacy of repaglinide was similar for patients consuming 2, 3 or 4 meals a day. Repaglinide showed additive effects when used in combination with other oral antidiabetic agents including metformin, troglitazone, rosiglitazone and pioglitazone, and intermediate-acting insulin (NPH) given at bedtime. In 1-year trials, the most common adverse events reported in repaglinide recipients (n = 1,228) were hypoglycaemia (16%), upper respiratory tract infection (10%), rhinitis (7%), bronchitis (6%) and headache (9%). The overall incidence of hypoglycaemia was similar to that recorded in patients receiving glibenclamide, glipizide or gliclazide (n = 597) [18%]; however, the incidence of serious hypoglycaemia appears to be slightly higher in sulphonylurea recipients. Unlike glibenclamide, the risk of hypoglycaemia in patients receiving repaglinide was not increased when a meal was missed in 1 trial. In conclusion, repaglinide is a useful addition to the other currently available treatments for type 2 diabetes mellitus. Preprandial repaglinide has displayed antihyperglycaemic efficacy at least equal to that of various sulphonylureas and is associated with a reduced risk of serious hypoglycaemia. It is well tolerated in a wide range of patients, including the elderly, even if a meal is missed. Furthermore, glycaemic control is improved when repaglinide is used in combination with metformin. Thus, repaglinide should be considered for use in any patient with type 2 diabetes mellitus whose blood glucose cannot be controlled by diet or exercise alone, or as an adjunct in patients whose glucose levels are inadequately controlled on metformin alone.

Antidiabetic and antioxidant activities of Nypa fruticans Wurmb. vinegar sample from Malaysia.

PubMed

Yusoff, Nor Adlin; Yam, Mun Fei; Beh, Hooi Kheng; Abdul Razak, Khairul Niza; Widyawati, Tri; Mahmud, Roziahanim; Ahmad, Mariam; Asmawi, Mohd Zaini

2015-08-01

To study the antidiabetic and antioxidant activities of nipa palm vinegar (NPV) used in traditional Malay medicine for treating diabetes. NPV was extracted using liquid-liquid extraction method and the obtained samples were subjected to antidiabetic studies using normal and streptozotocin-induced diabetic rat models whereas antidoxidant activities were investigated via in vitro antioxidant tests namely 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid free radicals scavenging activities and the reducing power assay. Single administration of NPV and its extracts were not effective in both normal and diabetic rats. In intraperitoneal glucose tolerance test, NPV and its aqueous extract showed significant blood glucose lowering effect. In the sub-acute study, compared with the diabetic control, aqueous extract of NPV showed the most notable blood glucose lowering effect (56.6%) and a significant improvement in serum insulin levels (79.8%, P < 0.05). To assess NPV's antioxidant activity, three in vitro antioxidant tests were employed: 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid free radical-scavenging assays, and the reducing power assay. Ethyl acetate extract had the greatest antioxidant potential and content of phenolic and flavonoid compounds. A linear positive correlation between the antioxidant parameters was observed. Chemical profiling analysis of aqueous extract of NPV revealed the presence of acetic acid (35.25%), the main active constituent which significantly contributed to the observed antidiabetic activity. Aqueous extract of NPV possesses antihyperglycaemic activities comparable to the metformin, while the ethyl acetate extract precipitated significant antioxidant effects attributable to its high phenolic content. These findings suggest that antioxidant compounds of NPV do not contribute much towards the overall observed antidiabetic effect. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Phospholipid complex enriched micelles: A novel drug delivery approach for promoting the antidiabetic effect of repaglinide.

PubMed

Kassem, Ahmed Alaa; Abd El-Alim, Sameh Hosam; Basha, Mona; Salama, Abeer

2017-03-01

To enhance the oral antidiabetic effect of repaglinide (RG), a newly emerging approach, based on the combination of phospholipid complexation and micelle techniques, was employed. Repaglinide-phospholipid complex (RG-PLC) was prepared by the solvent-evaporation method then characterized using Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XPRD). The results revealed obvious disappearance of the characteristic peaks of the prepared RG-PLCs confirming the formation of drug-phospholipid complex. RG-PLC enriched micelles (RG-PLC-Ms) were prepared by the solvent-evaporation technique employing poloxamer 188 as surfactant. The prepared RG-PLC-Ms showed high drug encapsulation efficiencies (93.81-99.38%), with nanometric particle diameters (500.61-665.32nm) of monodisperse distribution and high stability (Zeta potential < -29.8mV). The in vitro release of RG from RG-PLC-Ms was pH-dependant according to the release media. A higher release pattern was reported in pH=1.2 compared to a more retarded release in pH=6.8 owing to two different kinetics of drug release. Oral antidiabetic effect of two optimized RG-PLC-M formulations was evaluated in an alloxan-induced diabetic rat model for 7-day treatment protocol. The two investigated formulations depicted normal blood glucose, serum malondialdehyde and insulin levels as well as an improved lipid profile, at the end of daily oral treatment, in contrast to RG marketed tablets implying enhanced antidiabetic effect of the drug. Hence, phospholipid-complex enriched micelles approach holds a promising potential for promoting the antidiabetic effect of RG. Copyright © 2016 Elsevier B.V. All rights reserved.

Chrysin Induces Antidiabetic, Antidyslipidemic and Anti-Inflammatory Effects in Athymic Nude Diabetic Mice.

PubMed

Ramírez-Espinosa, Juan José; Saldaña-Ríos, Johann; García-Jiménez, Sara; Villalobos-Molina, Rafael; Ávila-Villarreal, Gabriela; Rodríguez-Ocampo, Angélica Nallelhy; Bernal-Fernández, Germán; Estrada-Soto, Samuel

2017-12-28

Extensive knowledge of diabetes and its complications is helpful to find new drugs for proper treatment to stop degenerative changes derived from this disease. In this context, chrysin (5,7-dihydroxyflavone) is a natural product that occurs in a variety of flowers and fruits with anti-inflammatory and antidiabetic effects, among others. Thus, a diabetic model in athymic nude mice was developed and used to establish the ability of chrysin to decrease the secretion of pro-inflammatory cytokines. Also, it was determined the acute (50 mg/kg) and sub-acute (50 mg/kg/day/10 days) antidiabetic and antihyperlipidemic activities after the period of time treatment. Results indicate that chrysin has significant acute antihyperglycemic and antidiabetic effects in nude diabetic mice ( p < 0.05). Moreover, triglyceride blood levels were reduced and IL-1β and TNF-α were diminished after 10 days' treatment compared with control group ( p < 0.05). In conclusion, it was found that chrysin could produce similar effects as metformin, a drug used for the treatment of diabetes, since both test samples decreased glucose and triglycerides levels, they impaired the generation of pro-inflammatory cytokines involved in the development of diabetes and its consequences, such as atherosclerosis and other cardiovascular diseases.

Heterocyclic Compounds: Effective α-Amylase and α-Glucosidase Inhibitors.

PubMed

Saeedi, Mina; Hadjiakhondi, Abbas; Nabavi, Seyed Mohammad; Manayi, Azadeh

2017-01-01

Diabetes Mellitus (DM) is a metabolic disease characterized by high blood sugar levels. Recently, it has emerged as an important and global health problem with long-term complications and high economic burden. α-Amylase (α-Amy) and α-glucosidase (α-Gls) are two enzymes which are involved in the hydrolysis of starch into sugars and disaccharides leading to the increase of blood glucose level. Hence, inhibition of α-amylase and α-glucosidase plays key role in the treatment of type 2 diabetes. Heterocyclic compounds -both synthetic and naturally occurring derivatives- possess efficient biological properties. At this juncture, they have demonstrated potent inhibitory activity against α-Amy and α-Gls and were found to be versatile tools for the development of novel anti-diabetic agents.

In vitro evaluation of anti-diabetic activity and cytotoxicity of chemically analysed Ocimum basilicum extracts.

PubMed

Kadan, Sleman; Saad, Bashar; Sasson, Yoel; Zaid, Hilal

2016-04-01

The aim of this study was to evaluate the role of glucose transporter-4 (GLUT4) in the anti-diabetic effects of methanol, hexane and dichloromethane extracts of the aerial parts of Ocimum basilicum (OB) and to analyze their phytochemical composition. Phytochemical analysis of the three extracts by GC/MS using the silylation derivatization technique revealed 53 compounds, 17 of them were found for the first time in OB. Cytotoxic and anti-diabetic properties of the extracts were evaluated using L6-GLUT4myc muscle cells stably expressing myc epitope at the exofacial loop (GLUT4). No cytotoxic effects were observed in treated cells up to 0.25 mg/ml extract as measured with MTT and LDH-leakage assays. GLUT4 translocation to the plasma membrane was elevated by 3.5 and 7 folds (-/+ insulin) after treatment with OB extracts for 20 h. Our findings suggest that the observed anti-diabetic properties of OB extracts are possibly mediated in part through one or more of the 17 new identified compound. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Sodium Glucose Co-transporter Type 2 (SGLT2) Inhibitors in CKD].

PubMed

Insalaco, Monica; Zanoli, Luca; Rastelli, Stefania; Lentini, Paolo; Rapisarda, Francesco; Fatuzzo, Pasquale; Castellino, Pietro; Granata, Antonio

2015-01-01

Among the new drugs used for the treatment of Diabetes Mellitus type 2, sodium-glucose cotransporter 2 (SGLT2) inhibitors represent a promising therapeutic option. Since their ability to lower glucose is proportional to GFR, their effect is reduced in patients with chronic kidney disease (CKD). The antidiabetic mechanism of these drugs is insulin-independent and, therefore, complimentary to that of others antihyperglicaemic agents. Moreover, SGLT2 inhibitors are able to reduce glomerular hyperfiltration, systemic and intraglomerular pressure and uric acid levels, with consequent beneficial effects on the progression of kidney disease in non diabetic patients as well. Only few studies have been performed to evaluate the effects of SGLT2 inhibitors in patients with CKD. Therefore, safety and efficacy of SGLT2 inhibitors should be better clarified in the setting of CKD. In this paper, we will review the use of SGLT2 inhibitors in diabetic patients, including those with CKD.

Inhibition of pancreatic lipase and amylase by extracts of different spices and plants.

PubMed

Sellami, Mohamed; Louati, Hanen; Kamoun, Jannet; Kchaou, Ali; Damak, Mohamed; Gargouri, Youssef

2017-05-01

The aim of this study is to search new anti-obesity and anti-diabetic agents from plant and spices crude extracts as alternative to synthetic drugs. The inhibitory effect of 72 extracts was evaluated, in vitro, on lipase and amylase activities. Aqueous extracts of cinnamon and black tea exhibited an appreciable inhibitory effect on pancreatic amylase with IC 50 values of 18 and 87 μg, respectively. Aqueous extracts of cinnamon and mint showed strong inhibitory effects against pancreatic lipase with IC 50 of 45 and 62 μg, respectively. The presence of bile salts and colipase or an excess of interface failed to restore the lipase activity. Therefore, the inhibition of pancreatic lipase, by extracts of spices and plants, belongs to an irreversible inhibition. Crude extract of cinnamon showed the strongest anti-lipase and anti-amylase activities which offer a prospective therapeutic approach for the management of diabetes and obesity.

Novel coumarin modified GLP-1 derivatives with enhanced plasma stability and prolonged in vivo glucose-lowering ability.

PubMed

Han, Jing; Sun, Lidan; Huang, Xun; Li, Zheng; Zhang, Chenyu; Qian, Hai; Huang, Wenlong

2014-12-01

The short biological half-life limits the therapeutic use of glucagon-like peptide-1 (GLP-1) and chemical modification to improve the interaction of peptides with serum albumin represents an effective strategy to develop long-acting peptide analogues. Coumarin, a natural product, is known to bind tightly to plasma proteins and possesses many biological activities. Therefore, we designed and synthesized a series of coumarin-modified GLP-1 derivatives, hypothesizing that conjugation with coumarin would retain the therapeutic effects and prolong the biological half-life of the conjugates. Four cysteine-modified GLP-1 analogues (1-4) were prepared using Gly8 -GLP-1(7-36)-NH2 peptide as a starting point. These analogues were conjugated with two coumarin maleimides to yield eight compounds (conjugates 6-13) for testing. Activation of human GLP-1 receptors, stability to enzymic inactivation in plasma and binding to human albumin were assessed in vitro. In vivo, effects on oral glucose tolerance tests (OGTT) in rats and on blood glucose levels in db/db mice were studied. Most conjugates showed well preserved receptor activation efficacy, enhanced albumin-binding properties and improved in vitro plasma stability and conjugate 7 was selected to undergo further assessment. In rats, conjugate 7 had a longer circulating t1/2 than exendin-4 or liraglutide. A prolonged antidiabetic effect of conjugate 7 was observed after OGTT in rats and a prolonged hypoglycaemic effect in db/db mice. Cysteine-specific coumarin conjugation with GLP-1 offers a useful approach to the development of long-acting incretin-based antidiabetic agents. Conjugate 7 is a promising long-lasting GLP-1 derivative deserving further investigation. © 2014 The British Pharmacological Society.

Novel coumarin modified GLP-1 derivatives with enhanced plasma stability and prolonged in vivo glucose-lowering ability

PubMed Central

Han, Jing; Sun, Lidan; Huang, Xun; Li, Zheng; Zhang, Chenyu; Qian, Hai; Huang, Wenlong

2014-01-01

Background and Purpose The short biological half-life limits the therapeutic use of glucagon-like peptide-1 (GLP-1) and chemical modification to improve the interaction of peptides with serum albumin represents an effective strategy to develop long-acting peptide analogues. Coumarin, a natural product, is known to bind tightly to plasma proteins and possesses many biological activities. Therefore, we designed and synthesized a series of coumarin-modified GLP-1 derivatives, hypothesizing that conjugation with coumarin would retain the therapeutic effects and prolong the biological half-life of the conjugates. Experimental Approach Four cysteine-modified GLP-1 analogues (1–4) were prepared using Gly8-GLP-1(7–36)-NH2 peptide as a starting point. These analogues were conjugated with two coumarin maleimides to yield eight compounds (conjugates 6–13) for testing. Activation of human GLP-1 receptors, stability to enzymic inactivation in plasma and binding to human albumin were assessed in vitro. In vivo, effects on oral glucose tolerance tests (OGTT) in rats and on blood glucose levels in db/db mice were studied. Key Results Most conjugates showed well preserved receptor activation efficacy, enhanced albumin-binding properties and improved in vitro plasma stability and conjugate 7 was selected to undergo further assessment. In rats, conjugate 7 had a longer circulating t1/2 than exendin-4 or liraglutide. A prolonged antidiabetic effect of conjugate 7 was observed after OGTT in rats and a prolonged hypoglycaemic effect in db/db mice. Conclusions and Implications Cysteine-specific coumarin conjugation with GLP-1 offers a useful approach to the development of long-acting incretin-based antidiabetic agents. Conjugate 7 is a promising long-lasting GLP-1 derivative deserving further investigation. PMID:25039358

Disordered haematopoiesis and athero-thrombosis

PubMed Central

Murphy, Andrew J.; Tall, Alan R.

2016-01-01

Abstract Atherosclerosis, the major underlying cause of cardiovascular disease, is characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries. Increased production and activation of monocytes, neutrophils, and platelets, driven by hypercholesterolaemia and defective high-density lipoproteins-mediated cholesterol efflux, tissue necrosis and cytokine production after myocardial infarction, or metabolic abnormalities associated with diabetes, contribute to atherogenesis and athero-thrombosis. This suggests that in addition to traditional approaches of low-density lipoproteins lowering and anti-platelet drugs, therapies directed at abnormal haematopoiesis, including anti-inflammatory agents, drugs that suppress myelopoiesis, and excessive platelet production, rHDL infusions and anti-obesity and anti-diabetic agents, may help to prevent athero-thrombosis. PMID:26869607

Novel therapies for the management of type 2 diabetes mellitus: part 1. pramlintide and bromocriptine-QR.

PubMed

Grunberger, George

2013-06-01

Several classes of antidiabetic agents have been introduced into the market place over the past dozen years. As our understanding of the underlying pathophysiology of type 2 diabetes has advanced, attempts have been made to address these defects specifically. This brief review focuses on our experience with two such pharmacological approaches: (i) a synthetic amylin analog addressing amylin deficiency; and (ii) a dopaminergic agonist, focused on enhancing the lowered dopaminergic tone in patients with type 2 diabetes. Importantly, the use of these agents is not associated with hypoglycemia or weight gain. © 2013 Wiley Publishing Asia Pty Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

Sulforaphane inhibits growth of human breast cancer cells and augments the therapeutic index of the chemotherapeutic drug, gemcitabine.

PubMed

Hussain, Arif; Mohsin, Javeria; Prabhu, Sathyen Alwin; Begum, Salema; Nusri, Qurrat El-Ain; Harish, Geetganga; Javed, Elham; Khan, Munawwar Ali; Sharma, Chhavi

2013-01-01

Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking or reversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer related death. One such promising chemopreventive agent which has attracted considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. The present study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent, gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the results by nuclear morphological examination. Further we analyzed the modulation of expression of Bcl-2 and COX-2 on treatment of these cells with SFN by RT-PCR. SFN showed cytotoxic effects on MCF-7 cells in a dose- and time-dependent manner via an apoptotic mode of cell death. In addition, a combinational treatment of SFN and gemcitabine on MCF-7 cells resulted in growth inhibition in a synergistic manner with a combination index (CI) <1. Notably, SFN was found to significantly downregulate the expression of Bcl-2, an anti-apoptotic gene, and COX-2, a gene involved in inflammation, in a time-dependent manner. These results indicate that SFN induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 and COX-2 respectively. The combination of SFN and gemcitabine may potentiate the efficacy of gemcitabine and minimize the toxicity to normal cells. Taken together, SFN may be a potent anti-cancer agent for breast cancer treatment.

SGLT2 inhibitors.

PubMed

Dardi, I; Kouvatsos, T; Jabbour, S A

2016-02-01

Diabetes mellitus is a serious health issue and an economic burden, rising in epidemic proportions over the last few decades worldwide. Although several treatment options are available, only half of the global diabetic population achieves the recommended or individualized glycemic targets. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with a novel insulin-independent action. SGLT2 is a transporter found in the proximal renal tubules, responsible for the reabsorption of most of the glucose filtered by the kidney. Inhibition of SGLT2 lowers the blood glucose level by promoting the urinary excretion of excess glucose. Due to their insulin-independent action, SGLT2 inhibitors can be used with any degree of beta-cell dysfunction or insulin resistance, related to a very low risk of hypoglycemia. In addition to improving glycemic control, SGLT2 inhibitors have been associated with a reduction in weight and blood pressure when used as monotherapy or in combination with other antidiabetic agents in patients with type 2 diabetes mellitus (T2DM). Treatment with SGLT2 inhibitors is usually well tolerated; however, they have been associated with an increased incidence of urinary tract and genital infections, although these infections are usually mild and easy to treat. SGLT2 inhibitors are a promising new option in the armamentarium of drugs for patients with T2DM. Copyright © 2015 Elsevier Inc. All rights reserved.

Consensus Statement on Dose Modifications of Antidiabetic Agents in Patients with Hepatic Impairment

PubMed Central

Gangopadhyay, Kalyan Kumar; Singh, Parminder

2017-01-01

Liver disease is an important cause of mortality in type 2 diabetes mellitus (T2DM). It is estimated that diabetes is the most common cause of liver disease in the United States. Virtually, entire spectrum of liver disease is seen in T2DM including abnormal liver enzymes, nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, and acute liver failure. The treatment of diabetes mellitus (DM) in cirrhotic patients has particular challenges as follows: (1) about half the patients have malnutrition; (2) patients already have advanced liver disease when clinical DM is diagnosed; (3) most of the oral antidiabetic agents (ADAs) are metabolized in the liver; (4) patients often have episodes of hypoglycemia. The aim of this consensus group convened during the National Insulin Summit 2015, Puducherry, was to focus on the challenges with glycemic management, with particular emphasis to safety of ADAs across stages of liver dysfunction. Published literature, product labels, and major clinical guidelines were reviewed and summarized. The drug classes included are biguanides (metformin), the second- or third-generation sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and currently available insulins. Consensus recommendations have been drafted for glycemic targets and dose modifications of all ADAs. These can aid clinicians in managing patients with diabetes and liver disease. PMID:28459036

An invertebrate hyperglycemic model for the identification of anti-diabetic drugs.

PubMed

Matsumoto, Yasuhiko; Sumiya, Eriko; Sugita, Takuya; Sekimizu, Kazuhisa

2011-03-30

The number of individuals diagnosed with type 2 diabetes mellitus, which is caused by insulin resistance and/or abnormal insulin secretion, is increasing worldwide, creating a strong demand for the development of more effective anti-diabetic drugs. However, animal-based screening for anti-diabetic compounds requires sacrifice of a large number of diabetic animals, which presents issues in terms of animal welfare. Here, we established a method for evaluating the anti-diabetic effects of compounds using an invertebrate animal, the silkworm, Bombyx mori. Sugar levels in silkworm hemolymph increased immediately after feeding silkworms a high glucose-containing diet, resulting in impaired growth. Human insulin and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, decreased the hemolymph sugar levels of the hyperglycemic silkworms and restored growth. Treatment of the isolated fat body with human insulin in an in vitro culture system increased total sugar in the fat body and stimulated Akt phosphorylation. These responses were inhibited by wortmannin, an inhibitor of phosphoinositide 3 kinase. Moreover, AICAR stimulated AMPK phosphorylation in the silkworm fat body. Administration of aminoguanidine, a Maillard reaction inhibitor, repressed the accumulation of Maillard reaction products (advanced glycation end-products; AGEs) in the hyperglycemic silkworms and restored growth, suggesting that the growth defect of hyperglycemic silkworms is caused by AGE accumulation in the hemolymph. Furthermore, we identified galactose as a hypoglycemic compound in jiou, an herbal medicine for diabetes, by monitoring its hypoglycemic activity in hyperglycemic silkworms. These results suggest that the hyperglycemic silkworm model is useful for identifying anti-diabetic drugs that show therapeutic effects in mammals.

Diverse mechanisms of antidiabetic effects of the different procyanidin oligomer types of two different cinnamon species on db/db mice.

PubMed

Chen, Liang; Sun, Peng; Wang, Ting; Chen, Kaixian; Jia, Qi; Wang, Heyao; Li, Yiming

2012-09-12

The procyanidin oligomers are thought to be responsible for the antidiabetic activity of cinnamon. To investigate the hypoglycemic effects of different procyanidin oligomer types, the procyanidin oligomer-rich extracts were prepared from two different cinnamon species. Using high-performance liquid chromatography with purified procyanidin oligomers as reference compounds, we found that the Cinnamomum cassia extract (CC-E) and Cinnamomum tamala extract (CT-E) were rich in B- and A-type procyanidin oligomers, respectively. In the experiment, 8-week-old diabetic (db/db) mice were gavaged with CC-E and CT-E (both 200 mg/kg per day) for 4 weeks. Both CC-E and CT-E exhibited antidiabetic effects. Moreover, histopathological studies of the pancreas, liver, and adipose tissue showed that CC-E promoted lipid accumulation in the adipose tissue and liver, whereas CT-E mainly improved the insulin concentration in the blood and pancreas.

[Use of new antidiabetics in the elderly population].

PubMed

Besse, Sarah; Besse, Arun; Jornayvaz, François R

2016-06-01

Over the last few years, we have noticed the arrival on the market of new antidiabetic treatments. These represent an potential advantage because of the increase in the prevalence of type 2 diabetes, particularly in the elderly population. Nevertheless, elderly patients have a number of frailties that should be considered in the treatment of this condition. There is a lack of literature in this population as elderly are frequently excluded from randomized controlled trials. Therefore, guidelines were developed based on the consensus of experts in geriatrics and diabetology for this specific population. We have to consider the potential benefits and adverse effects of the new antidiabetics in older patients.

Honey as a Potential Natural Antioxidant Medicine: An Insight into Its Molecular Mechanisms of Action

PubMed Central

Ahmed, Sarfraz; Sulaiman, Siti Amrah; Baig, Atif Amin; Ibrahim, Muhammad; Liaqat, Sana; Fatima, Saira; Jabeen, Sadia; Shamim, Nighat

2018-01-01

Honey clasps several medicinal and health effects as a natural food supplement. It has been established as a potential therapeutic antioxidant agent for various biodiverse ailments. Data report that it exhibits strong wound healing, antibacterial, anti-inflammatory, antifungal, antiviral, and antidiabetic effects. It also retains immunomodulatory, estrogenic regulatory, antimutagenic, anticancer, and numerous other vigor effects. Data also show that honey, as a conventional therapy, might be a novel antioxidant to abate many of the diseases directly or indirectly associated with oxidative stress. In this review, these wholesome effects have been thoroughly reviewed to underscore the mode of action of honey exploring various possible mechanisms. Evidence-based research intends that honey acts through a modulatory road of multiple signaling pathways and molecular targets. This road contemplates through various pathways such as induction of caspases in apoptosis; stimulation of TNF-α, IL-1β, IFN-γ, IFNGR1, and p53; inhibition of cell proliferation and cell cycle arrest; inhibition of lipoprotein oxidation, IL-1, IL-10, COX-2, and LOXs; and modulation of other diverse targets. The review highlights the research done as well as the apertures to be investigated. The literature suggests that honey administered alone or as adjuvant therapy might be a potential natural antioxidant medicinal agent warranting further experimental and clinical research. PMID:29492183

Comparative Analysis of Chemical Profile, Antioxidant, In-vitro and In-vivo Antidiabetic Activities of Juniperus foetidissima Willd. and Juniperus sabina L.

PubMed Central

Orhan, Nilüfer; Deliorman Orhan, Didem; Gökbulut, Alper; Aslan, Mustafa; Ergun, Fatma

2017-01-01

Fruit and leaves of junipers are commonly used internally as tea and pounded fruits are eaten to lower blood glucose levels in Anatolia. Thus, we aimed to evaluate antidiabetic and antioxidant potential and the chemical profile of Juniperus foetidissima Willd. and J. sabina L. in this study. In-vitro antidiabetic activities of leaf and fruit extracts were examined by their inhibitory activity on α-glucosidase and α-amylase enzymes. Then, in-vivo antidiabetic activities of leaf and fruit extracts of Juniperus species were investigated on streptozotocin-induced diabetic rats. Additionally, antioxidant activities (phosphomolybdenum, ferric-reducing antioxidant power and ABTS radical scavenging activity assays), phytochemical screening tests and high performance liquid chromatography analysis (HPLC) were done. In-vitro enzyme inhibitory effects of the extracts were supported by the results of in-vivo antidiabetic activity studies. Phytochemical screening tests indicated presence of flavonoids, tannins, terpenoids and carbohydrates in the extracts. Amentoflavone was identified as the major compound in the extracts and content of amentoflavone was determined. As a result, Juniperus extracts and its active constituents might be beneficial for diabetes and its complications. PMID:29844777

Averrhoa bilimbi Linn.: A review of its ethnomedicinal uses, phytochemistry, and pharmacology

PubMed Central

Alhassan, Alhassan Muhammad; Ahmed, Qamar Uddin

2016-01-01

Averrhoa bilimbi Linn. is principally cultivated for medicinal purposes in many tropical and subtropical countries of the world. Literature survey about this plant shows that A. bilimbi is mainly used as a folk medicine in the treatment of diabetes mellitus, hypertension, and as an antimicrobial agent. The prime objective of this review is to accumulate and organize literature based on traditional claims and correlate those with current findings on the use of A. bilimbi in the management of different ailments. Through interpreting already published scientific manuscripts (1995 through 2015) retrieved from the different scientific search engines, namely Medline, PubMed, EMBASE, and Science Direct databases, published articles and reports covering traditional and scientific literature related to A. bilimbi's potential role against various ailments have been thoroughly evaluated, interpreted, and discussed. Several pharmacological studies have demonstrated the ability of this plant to act as antidiabetic, antihypertensive, thrombolytic, antimicrobial, antioxidant, hepatoprotective, and hypolipidemic agent. A. bilimbi holds great value in the complementary and alternative medicine as evidenced by the substantial amount of research on it. Therefore, we aimed to compile an up-to-date and comprehensive review of A. bilimbi that covers its traditional and folk medicine uses, phytochemistry, and pharmacology. Hence, this paper presents an up-to-date and comprehensive review of the ethnomedicinal uses, different chemical constituents, and pharmacological activities of A. bilimbi. So far, the biologically active agents have not been isolated from this plant and this can be a good scientific study for the future antidiabetic, antihypertensive, and antimicrobial implications. Hence, this review targets at emphasizing the diverse traditional claims and pharmacological activities of A. bilimbi with respect to carrying out more scientific studies to isolate active principles through advanced technology. PMID:28216948

Averrhoa bilimbi Linn.: A review of its ethnomedicinal uses, phytochemistry, and pharmacology.

PubMed

Alhassan, Alhassan Muhammad; Ahmed, Qamar Uddin

2016-01-01

Averrhoa bilimbi Linn. is principally cultivated for medicinal purposes in many tropical and subtropical countries of the world. Literature survey about this plant shows that A. bilimbi is mainly used as a folk medicine in the treatment of diabetes mellitus, hypertension, and as an antimicrobial agent. The prime objective of this review is to accumulate and organize literature based on traditional claims and correlate those with current findings on the use of A. bilimbi in the management of different ailments. Through interpreting already published scientific manuscripts (1995 through 2015) retrieved from the different scientific search engines, namely Medline, PubMed, EMBASE, and Science Direct databases, published articles and reports covering traditional and scientific literature related to A. bilimbi 's potential role against various ailments have been thoroughly evaluated, interpreted, and discussed. Several pharmacological studies have demonstrated the ability of this plant to act as antidiabetic, antihypertensive, thrombolytic, antimicrobial, antioxidant, hepatoprotective, and hypolipidemic agent. A. bilimbi holds great value in the complementary and alternative medicine as evidenced by the substantial amount of research on it. Therefore, we aimed to compile an up-to-date and comprehensive review of A. bilimbi that covers its traditional and folk medicine uses, phytochemistry, and pharmacology. Hence, this paper presents an up-to-date and comprehensive review of the ethnomedicinal uses, different chemical constituents, and pharmacological activities of A. bilimbi . So far, the biologically active agents have not been isolated from this plant and this can be a good scientific study for the future antidiabetic, antihypertensive, and antimicrobial implications. Hence, this review targets at emphasizing the diverse traditional claims and pharmacological activities of A. bilimbi with respect to carrying out more scientific studies to isolate active principles through advanced technology.

Population PKPD modelling of the long-term hypoglycaemic effect of gliclazide given as a once-a-day modified release (MR) formulation

PubMed Central

Frey, N; Laveille, C; Paraire, M; Francillard, M; Holford, N H G; Jochemsen, Roeline

2003-01-01

Aims To study the relationship between the pharmacokinetics (PK) of gliclazide and its long-term pharmacodynamic (PD) effect in a large population of Type 2 diabetic patients and to identify factors predicting intersubject variability. Methods A PKPD database of 634 Type 2 diabetic patients with a total of 5258 fasting plasma glucose (FPG) samples was built up from the data collected during the clinical development of a modified release formulation of gliclazide (gliclazide MR). The PKPD analysis used a nonlinear mixed effect modelling approach. A mixture model was used to identify patients with a FPG response to treatment. In patients identified as responders, the decrease in FPG was related to gliclazide exposure (AUC) by an Emax relationship. An effect compartment was used to describe the link between PK and PD. A linear disease-progression model was used to assess the glycaemic deterioration observable over several months of treatment. Simulations were performed to evaluate the predictive performance of the PKPD model and to illustrate the time course of the antidiabetic effect of gliclazide MR. Results Disease state was found to be the main explanatory factor for intersubject variability in response to gliclazide. The percentage of responders to gliclazide, used as monotherapy, increased inversely to the number of classes of antidiabetic agents received prior to entry in the studies. In responders, the initial dose (30 mg) of the gliclazide MR dosing regimen induced half of the maximum hypoglycaemic effect. The equilibration half-life between the PK and PD steady states was 3 weeks (intersubject variability of 84%). The rate of disease progression was 0.84 mmol l−1 year−1 (intersubject variability 143%). The PKPD model adequately predicted the FPG profiles of 234 patients who received the current formulation of gliclazide. Simulation of a 1-year parallel dose ranging clinical trial illustrated the influence of dose, time and type of previous antidiabetic treatment on the percentage of patients with clinically significant improvement of blood glucose control. Conclusions This population PKPD analysis has characterized the relationship between the exposure to gliclazide and its long-term hypoglycaemic effect, and has established that the intersubject variability in response is mostly related to disease state. These results underline the clinical interest of quickly increasing the dose of gliclazide MR according to the response to treatment in order to achieve effective blood glucose control. PMID:12580986

Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats.

PubMed

Akhtar, Muhammad Tayyab; Bin Mohd Sarib, Mohamad Syakir; Ismail, Intan Safinar; Abas, Faridah; Ismail, Amin; Lajis, Nordin Hj; Shaari, Khozirah

2016-08-09

Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese-diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

Antinociceptive, anti-inflammatory and antidiabetic effects of Bryophyllum pinnatum (Crassulaceae) leaf aqueous extract.

PubMed

Ojewole, John A O

2005-05-13

In order to scientifically appraise some of the ethnomedical uses of Bryophyllum pinnatum leaves, the present study was undertaken to investigate the antinociceptive, anti-inflammatory and antidiabetic properties of the plant's leaf aqueous extract in experimental animal models. The antinociceptive effect of the herb's leaf extract was evaluated by the 'hot-plate' and 'acetic acid' test models of pain in mice. The anti-inflammatory and antidiabetic effects of the plant's extract were investigated in rats, using fresh egg albumin-induced pedal (paw) oedema, and streptozotocin (STZ)-induced diabetes mellitus. Diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used respectively as reference drugs for comparison. Bryophyllum pinnatum leaf aqueous extract (BPE, 25-800 mg/kg i.p.) produced significant (P<0.05-0.001) antinociceptive effects against thermally- and chemically-induced nociceptive pain stimuli in mice. The plant extract (BPE, 25-800 mg/kg p.o. or i.p.) also significantly (P<0.05-0.001) inhibited fresh egg albumin-induced acute inflammation and caused significant (P<0.05-0.001) hypoglycaemia in rats. The results of this experimental animal study suggest that Bryophyllum pinnatum leaf aqueous extract possesses antinociceptive, anti-inflammatory and hypoglycaemic properties. The different flavonoids, polyphenols, triterpenoids and other chemical constituents of the herb are speculated to account for the observed antinociceptive, anti-inflammatory and antidiabetic properties of the plant.

Zinc complexes developed as metallopharmaceutics for treating diabetes mellitus based on the bio-medicinal inorganic chemistry.

PubMed

Yoshikawa, Yutaka; Yasui, Hiroyuki

2012-01-01

Biological trace metals such as iron, zinc, copper, and manganese are essential to life and health of humans, and the success of platinum drugs in the cancer chemotherapy has rapidly grown interest in developing inorganic pharmaceutical agents in medicinal chemistry, that is, medicinal inorganic chemistry, using essential elements and other biological trace metals. Transition metal complexes with unique chemical structures may be useful alternatives to the drugs available to address some of the incurable diseases. In this review, we emphasize that metal complexes are an expanding of interest in the research field of treatment of diabetes mellitus. Especially, orally active anti-diabetic and anti-metabolic syndrome zinc complexes have been developed and progressed since the discovery in 2001, where several highly potent anti-diabetic zinc complexes with different coordination structures have quite recently been disclosed, using experimental diabetic animals. In all of the complexes discussed, zinc is found to be biologically active and function by interacting with some target proteins related with diabetes mellitus. The design and screening of zinc complexes with higher activity is not efficient without consideration of the translational research. For the development of a clinically useful metallopharmaceutics, the research of zinc complexes on the long-term toxicity including side effects, clear-cut evidence of target molecule for the in vivo pharmacological action, and good pharmacokinetic property are essential in the current and future studies.

Isoquercetin ameliorates hyperglycemia and regulates key enzymes of glucose metabolism via insulin signaling pathway in streptozotocin-induced diabetic rats.

PubMed

Jayachandran, Muthukumaran; Zhang, Tongze; Ganesan, Kumar; Xu, Baojun; Chung, Stephen Sum Man

2018-06-15

Among the foremost common flavonoids within the human diet, quercetin glycosides possess neuroprotective, cardioprotective, anti-oxidative, chemopreventive, and anti-allergic properties. Isoquercetin is one such promising candidate with anti-diabetic potential. However, complete studies of its molecular action on insulin signaling pathway and carbohydrate metabolizing enzymes remain unclear. Hence, we have designed this study to accumulate the experimental evidence in support of anti-diabetic effects of isoquercetin. Male albino Wistar rats were divided into seven groups. Rats (Groups 3-7) were administered a single intraperitoneal injection of streptozotocin (STZ; 40 mg/kg b.w) to induce diabetes mellitus. As an extension, STZ rats received isoquercetin at three different doses (20, 40 and 80 mg/kg b.w), and Group 7 rats received glibenclamide (standard drug) (600 μg/kg b.w). The results showed that STZ exaggerated blood sugar, decreased insulin, altered metabolizing enzymes, and impaired the mRNA expression of insulin signaling genes and carbohydrate metabolizing enzyme genes. Supplementation with isoquercetin significantly normalized blood sugar levels, insulin and regulated the mRNA expression of insulin signaling genes and carbohydrate metabolizing enzyme genes. The results achieved with isoquercetin are similar to that of standard drug glibenclamide. The findings suggest isoquercetin could be a possible therapeutic agent for treating diabetes mellitus in the near future. Copyright © 2018 Elsevier B.V. All rights reserved.

Cinnamaldehyde--a potential antidiabetic agent.

PubMed

Subash Babu, P; Prabuseenivasan, S; Ignacimuthu, S

2007-01-01

Cinnamonum zeylanicum (cinnamon) is widely used in traditional system of medicine to treat diabetes in India. The present study was carried out to isolate and identify the putative antidiabetic compounds based on bioassay-guided fractionation; the compound identified decreased the plasma glucose levels. The active compound was purified by repeat column and structure of cinnamaldehyde was determined on the basis of chemical and physiochemical evidence. The LD(50) value of cinnamaldehyde was determined as 1850+/-37 mg/kg bw. Cinnamaldehyde was administered at different doses (5, 10 and 20 mg/kg bw) for 45 days to streptozotocin (STZ) (60 mg/kg bw)-induced male diabetic wistar rats. It was found that plasma glucose concentration was significantly (p<0.05) decreased in a dose-dependent manner (63.29%) compared to the control. In addition, oral administration of cinnamaldehyde (20 mg/kg bw) significantly decreased glycosylated hemoglobin (HbA(1C)), serum total cholesterol, triglyceride levels and at the same time markedly increased plasma insulin, hepatic glycogen and high-density lipoprotein-cholesterol levels. Also cinnamaldehyde restored the altered plasma enzyme (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase and acid phosphatase) levels to near normal. Administration of glibenclamide, a reference drug (0.6 mg/kg bw) also produced a significant (p<0.05) reduction in blood glucose concentration in STZ-induced diabetic rats. The results of this experimental study indicate that cinnamaldehyde possesses hypoglycemic and hypolipidemic effects in STZ-induced diabetic rats.

Comparative effectiveness of vildagliptin in combination with other oral anti-diabetes agents in usual-care conditions: the EDGE-Latin America study.

PubMed

Mendivil, Carlos O; Márquez-Rodríguez, Eduardo; Angel, Iván D; Paz, Gustavo; Rodríguez, Cruz; Almada, Jorge; Szyskowsky, Ofelia

2014-09-01

To assess the proportion of patients on vildagliptin add-on dual therapy who respond to treatment over a 12 month follow-up, relative to comparator oral anti-diabetes dual therapy, in a usual care setting. Participants were patients with type 2 diabetes (T2DM) aged 18 years and older from 311 centers in Argentina, Colombia, Ecuador, Mexico and Venezuela. Patients were taking monotherapy with an oral anti-diabetes drug (OAD), and were prescribed a new add-on OAD based on the judgment of their personal physician. According to this choice, patients were assigned to one of the two cohorts: vildagliptin or comparator OADs. The primary endpoint was the proportion of patients achieving an A1c drop >0.3% without edema, hypoglycemia, weight gain or discontinuation due to gastrointestinal (GI) events. The secondary endpoint was the proportion of patients with baseline A1c ≥7% who reached the goal of an A1c <7% without hypoglycemia or weight gain. The per-protocol population (a subset of the intention-to-treat population that excluded patients with pre-specified protocol deviations) comprised 3773 patients, 3002 in the vildagliptin cohort and 771 in the comparator cohort. The proportion of patients reaching the primary endpoint was higher in the vildagliptin cohort (60.3%) than the comparator cohort (50.7%), OR 1.48 (95% CI: 1.25-1.73). The same was observed for the secondary endpoint (44.8 versus 33.1%) OR 1.64 (95% CI: 1.37-1.98). The incidence of adverse events was low and similar between treatment cohorts. In a usual care setting, patients treated with a vildagliptin combination succeeded in lowering A1c to <7%, without weight gain, hypoglycemia or peripheral edema more often than patients treated with comparator combinations, without increased risk of adverse events. Key limitations are the observational nature of the study and its relatively limited 12 month timeframe.

Comparative study of antidiabetic activity of Cajanus cajan and Tamarindus indica in alloxan-induced diabetic mice with a reference to in vitro antioxidant activity

PubMed Central

Nahar, Laizuman; Nasrin, Fatema; Zahan, Ronok; Haque, Anamul; Haque, Ekramul; Mosaddik, Ashik

2014-01-01

Background: Oxidative stress not only develops complications in diabetic (type 1 and type 2) but also contributes to beta cell destruction in type 2 diabetes in insulin resistance hyperglycemia. Glucose control plays an important role in the pro-oxidant/antioxidant balance. Some antidiabetic agents may by themselves have antioxidant properties independently of their role on glucose control. Objective: The present investigation draws a comparison of the protective antioxidant activity, total phenol content and the antihyperglycemic activity of the methanolic extract of Cajanus cajan root (MCC) and Tamarindus indica seeds (MTI). Materials and Methods: Antidiabetic potentials of the plant extracts were evaluated in alloxan-induced diabetic Swiss albino mice. The plant extracts at the doses of 200 and 400 mg/kg body weight was orally administered for glucose tolerance test during 1-hour study and hypoglycemic effect during 5-day study period in comparison with reference drug Metformin HCl (50 mg/kg). In vitro antioxidant potential of MCC and MTI was investigated by using 1, 1- diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity at 517 nm. Total phenolic content, total antioxidant capacity and reducing power activity was also assayed. Results: There was a significant decrease in fasting serum glucose level (P < 0.001), reduction in blood glucose level (P < 0.001) in 5-days study, observed in the alloxan-induced diabetic mice. The reduction efficacy of blood glucose level of both the extracts is proportional to their dose but MCC is more potent than MTI. Antioxidant study and quantification of phenolic compound of both the extracts revealed that they have high antioxidant capacity. Conclusion: These studies showed that MCC and MTI have both hypoglycemic and antioxidant potential but MCC is more potent than MTI. The present study suggests that both MCC and MTI could be used in managing oxidative stress. PMID:24761124

Hibiscus sabdariffa L. - a phytochemical and pharmacological review.

PubMed

Da-Costa-Rocha, Inês; Bonnlaender, Bernd; Sievers, Hartwig; Pischel, Ivo; Heinrich, Michael

2014-12-15

Hibiscus sabdariffa L. (Hs, roselle; Malvaceae) has been used traditionally as a food, in herbal drinks, in hot and cold beverages, as a flavouring agent in the food industry and as a herbal medicine. In vitro and in vivo studies as well as some clinical trials provide some evidence mostly for phytochemically poorly characterised Hs extracts. Extracts showed antibacterial, anti-oxidant, nephro- and hepato-protective, renal/diuretic effect, effects on lipid metabolism (anti-cholesterol), anti-diabetic and anti-hypertensive effects among others. This might be linked to strong antioxidant activities, inhibition of α-glucosidase and α-amylase, inhibition of angiotensin-converting enzymes (ACE), and direct vaso-relaxant effect or calcium channel modulation. Phenolic acids (esp. protocatechuic acid), organic acid (hydroxycitric acid and hibiscus acid) and anthocyanins (delphinidin-3-sambubioside and cyanidin-3-sambubioside) are likely to contribute to the reported effects. More well designed controlled clinical trials are needed which use phytochemically characterised preparations. Hs has an excellent safety and tolerability record. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of capping agents: Structural, optical and biological properties of ZnO nanoparticles

NASA Astrophysics Data System (ADS)

Javed, Rabia; Usman, Muhammad; Tabassum, Saira; Zia, Muhammad

2016-11-01

Different biological activities of capped and uncapped ZnO nanoparticles were investigated, and the effects of potential capping agents on these biological activities were studied. ZnO nanoparticles were synthesized and capped by polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) using a simple chemical method of co-precipitation. Characterization by X-ray diffraction (XRD), Fourier transform Infrared spectroscopy (FTIR) and UV-vis spectroscopy confirmed the crystallinity, size, functional group, and band gap of synthesized nanoparticles. Reduction in size occurred from 34 nm to 26 nm due to surfactant. Results of all biological activities indicated significantly higher values in capped as compared to uncapped nanoparticles. Antibacterial activity against Staphylococcus aureus (ATCC 6538), Bacillus subtilis (ATCC 6633), Escherichia coli (ATCC15224), and Acetobacter was obtained. This activity was more prominent against Gram-positive bacteria, and ZnO-PVP nanoparticles elucidated highest antibacterial activity (zone of inhibition 17 mm) against Gram-positive, Bacillus subtilis species. Antioxidant activities including total flavonoid content, total phenolic content, total antioxidant capacity, total reducing power and %age inhibition of DPPH, and antidiabetic activity against α-amylase enzyme found to be exhibited highest by ZnO-PEG nanoparticles.

C-Aryl glucoside SGLT2 inhibitors containing a biphenyl motif as potential anti-diabetic agents.

PubMed

Ding, Yuyang; Mao, Liufeng; Xu, Dengfeng; Xie, Hui; Yang, Ling; Xu, Hongjiang; Geng, Wenjun; Gao, Yong; Xia, Chunguang; Zhang, Xiquan; Meng, Qingyi; Wu, Donghai; Zhao, Junling; Hu, Wenhui

2015-07-15

A series of highly active C-aryl glucoside SGLT2 inhibitors containing a biphenyl motif were designed and synthesized for biological evaluation. Among the compounds tested, compound 16l demonstrated high inhibitory activity against SGLT2 (IC50=1.9 nM) with an excellent pharmacokinetic profile. Further study indicated that the in vivo efficacy of compound 16l was comparable to that of dapagliflozin, suggesting that further development would be worthwhile. Copyright © 2015 Elsevier Ltd. All rights reserved.

The novel gluconeogenesis inhibitors FR225659 and related compounds that originate from Helicomyces sp. No. 19353. I. Taxonomy, fermentation, isolation and physico-chemical properties.

PubMed

Ohtsu, Yoshihiro; Sasamura, Hiromi; Tsurumi, Yasuhisa; Yoshimura, Seiji; Takase, Shigehiro; Hashimoto, Michizane; Shibata, Toshihiro; Hino, Motohiro; Fujii, Takashi

2003-08-01

FR225659 and four related compounds are novel gluconeogenesis inhibitors that consist of a novel acyl-group and three abnormal amino acids. They were isolated from the culture broth of Helicomyces sp. No. 19353 and can be purified by absorptive resin and reverse-phase column chromatography. They are potent inhibitors of gluconeogenesis in primary cultured rat hepatocytes and thus may be useful as anti-diabetic agents.

Antidiabetic Properties, Bioactive Constituents, and Other Therapeutic Effects of Scoparia dulcis.

PubMed

Pamunuwa, Geethi; Karunaratne, D Nedra; Waisundara, Viduranga Y

2016-01-01

This review discusses the antidiabetic activities of Scoparia dulcis as well as its antioxidant and anti-inflammatory properties in relation to the diabetes and its complications. Ethnomedical applications of the herb have been identified as treatment for jaundice, stomach problems, skin disease, fever, and kidney stones, reproductory issues, and piles. Evidence has been demonstrated through scientific studies as to the antidiabetic effects of crude extracts of S. dulcis as well as its bioactive constituents. The primary mechanisms of action of antidiabetic activity of the plant and its bioactive constituents are through α-glucosidase inhibition, curbing of PPAR-γ and increased secretion of insulin. Scoparic acid A, scoparic acid D, scutellarein, apigenin, luteolin, coixol, and glutinol are some of the compounds which have been identified as responsible for these mechanisms of action. S. dulcis has also been shown to exhibit analgesic, antimalarial, hepatoprotective, sedative, hypnotic, antiulcer, antisickling, and antimicrobial activities. Given this evidence, it may be concluded that S. dulcis could be promoted among the masses as an alternative and complementary therapy for diabetes, provided further scientific studies on the toxicological and pharmacological aspects are carried out through either in vivo or clinical means.

Antidiabetic Properties, Bioactive Constituents, and Other Therapeutic Effects of Scoparia dulcis

PubMed Central

Karunaratne, D. Nedra

2016-01-01

This review discusses the antidiabetic activities of Scoparia dulcis as well as its antioxidant and anti-inflammatory properties in relation to the diabetes and its complications. Ethnomedical applications of the herb have been identified as treatment for jaundice, stomach problems, skin disease, fever, and kidney stones, reproductory issues, and piles. Evidence has been demonstrated through scientific studies as to the antidiabetic effects of crude extracts of S. dulcis as well as its bioactive constituents. The primary mechanisms of action of antidiabetic activity of the plant and its bioactive constituents are through α-glucosidase inhibition, curbing of PPAR-γ and increased secretion of insulin. Scoparic acid A, scoparic acid D, scutellarein, apigenin, luteolin, coixol, and glutinol are some of the compounds which have been identified as responsible for these mechanisms of action. S. dulcis has also been shown to exhibit analgesic, antimalarial, hepatoprotective, sedative, hypnotic, antiulcer, antisickling, and antimicrobial activities. Given this evidence, it may be concluded that S. dulcis could be promoted among the masses as an alternative and complementary therapy for diabetes, provided further scientific studies on the toxicological and pharmacological aspects are carried out through either in vivo or clinical means. PMID:27594892

Nanostructured Lipid Carriers Loaded with Baicalin: An Efficient Carrier for Enhanced Antidiabetic Effects

PubMed Central

Shi, Feng; Wei, Zheng; Zhao, Yingying; Xu, Ximing

2016-01-01

Context: Recent studies have demonstrated that baicalin has antihyperglycemic effects by inhibiting lipid peroxidation. Baicalin is low hydrophilic and poorly absorbed after oral administration. Thus, a suitable formulation is highly desired to overcome the disadvantages of baicalin. Objective: The objective of this work was to prepare baicalin-loaded nanostructured lipid carriers (B-NLCs) for enhanced antidiabetic effects. Materials and Methods: B-NLCs were prepared by high-pressure homogenization method using Precirol as the solid lipid and Miglyol as the liquid lipid. The properties of the NLCs, such as particle size, zeta potential (ZP), and drug encapsulation efficiency (EE), were investigated. The morphology of NLCs was observed by transmission electron microscopy. In addition, drug release and antidiabetic activity were also studied. Results: The results revealed that B-NLCs particles were uniformly in the nanosize range and of spherical morphology with a mean size of 92 ± 3.1 nm, a ZP of −31.35 ± 3.08 mV, and an EE of 85.29 ± 3.42%. Baicalin was released from NLCs in a sustained manner. In addition, B-NLCs showed a significantly higher antidiabetic efficacy compared with baicalin. Conclusion: B-NLCs described in this study are well-suited for the delivery of baicalin. SUMMARY Currently, herbal medicines have attracted increasing attention as a complementary approach for type 2 diabetesBaicalin has antihyperglycemic effects by inhibiting lipid peroxidationA suitable formulation is highly desired to overcome the disadvantages (poor solubility and low bioavailability) of baicalinNanostructured lipid carriers could enhance the antidiabetic effects of baicalin. Abbreviations used: B-NLCs: Baicalin-Loaded Nanostructured Lipid Carriers, B-SUS: Baicalin Water Suspension, EE: Encapsulation Efficiency, FBG: Fasting Blood Glucose, HbAlc: Glycosylated Hemoglobin, HPLC: High-performance Liquid Chromatography; NLCs: Nanostructured Lipid Carriers, PI: Polydispersity Index, SD: Sprague-Dawley, SLNs: Solid lipid nanoparticles, STZ: Streptozotocin, TC: Total cholesterol, TEM: Transmission Electron Microscope, TG: Total Triglyceride, ZP: Zeta Potential. PMID:27601850

Nanostructured Lipid Carriers Loaded with Baicalin: An Efficient Carrier for Enhanced Antidiabetic Effects.

PubMed

Shi, Feng; Wei, Zheng; Zhao, Yingying; Xu, Ximing

2016-01-01

Recent studies have demonstrated that baicalin has antihyperglycemic effects by inhibiting lipid peroxidation. Baicalin is low hydrophilic and poorly absorbed after oral administration. Thus, a suitable formulation is highly desired to overcome the disadvantages of baicalin. The objective of this work was to prepare baicalin-loaded nanostructured lipid carriers (B-NLCs) for enhanced antidiabetic effects. B-NLCs were prepared by high-pressure homogenization method using Precirol as the solid lipid and Miglyol as the liquid lipid. The properties of the NLCs, such as particle size, zeta potential (ZP), and drug encapsulation efficiency (EE), were investigated. The morphology of NLCs was observed by transmission electron microscopy. In addition, drug release and antidiabetic activity were also studied. The results revealed that B-NLCs particles were uniformly in the nanosize range and of spherical morphology with a mean size of 92 ± 3.1 nm, a ZP of -31.35 ± 3.08 mV, and an EE of 85.29 ± 3.42%. Baicalin was released from NLCs in a sustained manner. In addition, B-NLCs showed a significantly higher antidiabetic efficacy compared with baicalin. B-NLCs described in this study are well-suited for the delivery of baicalin. Currently, herbal medicines have attracted increasing attention as a complementary approach for type 2 diabetesBaicalin has antihyperglycemic effects by inhibiting lipid peroxidationA suitable formulation is highly desired to overcome the disadvantages (poor solubility and low bioavailability) of baicalinNanostructured lipid carriers could enhance the antidiabetic effects of baicalin. Abbreviations used: B-NLCs: Baicalin-Loaded Nanostructured Lipid Carriers, B-SUS: Baicalin Water Suspension, EE: Encapsulation Efficiency, FBG: Fasting Blood Glucose, HbAlc: Glycosylated Hemoglobin, HPLC: High-performance Liquid Chromatography; NLCs: Nanostructured Lipid Carriers, PI: Polydispersity Index, SD: Sprague-Dawley, SLNs: Solid lipid nanoparticles, STZ: Streptozotocin, TC: Total cholesterol, TEM: Transmission Electron Microscope, TG: Total Triglyceride, ZP: Zeta Potential.

Antidiabetic effect of Achillea millefollium through multitarget interactions: α-glucosidases inhibition, insulin sensitization and insulin secretagogue activities.

PubMed

Chávez-Silva, Fabiola; Cerón-Romero, Litzia; Arias-Durán, Luis; Navarrete-Vázquez, Gabriel; Almanza-Pérez, Julio; Román-Ramos, Rubén; Ramírez-Ávila, Guillermo; Perea-Arango, Irene; Villalobos-Molina, Rafael; Estrada-Soto, Samuel

2018-02-15

Achillea millefolium L. (Asteraceae) is a perennial herb used in Mexican folk medicine for treatment of several pathologies, including inflammatory and spasmodic gastrointestinal disorders, hepatobiliary complaints, overactive cardiovascular, respiratory ailments and diabetes. To evaluate the potential antidiabetic effect in vivo and to establish the potential mode of action through in vitro approaches of Achillea millefolium. The antidiabetic effect of hydroalcoholic extract of Achillea millefolium (HAEAm) was evaluated on the oral glucose tolerance tests, in normoglycemic and experimental Type 2 diabetic mice models. In addition, we evaluated the possible mode of action in in vitro assays to determine α-glucosidases inhibition, the insulin secretion and calcium mobilization in RINm5F cells and PPARγ and GLUT4 expression in 3T3-L1 cells. HAEAm showed significant glucose diminution on oral glucose tolerance test and in acute experimental Type 2 diabetic assay with respect to the control (p < 0.05). In addition, HAEAm promoted the α-glucosidases inhibition by 55% at 1mg/ml respect to control. On the other hand, HAEAm increased the PPARγ (five-times) and GLUT4 (two-fold) relative expression than control (p < 0.05). Finally, HAEAm significantly increased the insulin secretion and [Ca 2+ ] i compared with control. The HAEAm possesses in vivo antidiabetic effect, having such effect through multitarget modes of action that involve antihyperglycemic (α-glucosidases inhibition), hypoglycemic (insulin secretion) and potential insulin sensitizer (PPARγ/GLUT4 overexpression) actions. Copyright © 2017 Elsevier B.V. All rights reserved.

Associations between labial and whole salivary flow rates, systemic diseases and medications in a sample of older people.

PubMed

Smidt, Dorte; Torpet, Lis Andersen; Nauntofte, Birgitte; Heegaard, Karen Margrethe; Pedersen, Anne Marie Lynge

2010-10-01

To investigate the associations between age, gender, systemic diseases, medications and labial and whole salivary flow rates in older people. Unstimulated labial (LS) and unstimulated (UWS) and chewing-stimulated (SWS) whole salivary flow rates were measured in 389 randomly selected community-dwelling Danish women and 279 men aged 65-97 years. Systemic diseases, medications (coded according to the Anatomical Therapeutic Chemical (ATC) Classification System), tobacco and alcohol consumption were registered. The number of diseases and medications was higher and UWS lower in the older age groups. On average, women were slightly older, had more diseases, higher medication intake and lower UWS, SWS and LS than men. High number of diseases and medications was associated with low UWS, SWS and LS. In the healthy (14%) and nonmedicated (19%) participants, flow rates were not associated with age and gender, apart from SWS being lower in nonmedicated women. Low UWS were associated with psychiatric and respiratory disorders, type 2 diabetes and intake of psycholeptics, psychoanaleptics (especially SRRIs), respiratory agents, oral antidiabetics (particularly sulfonylureas), magnesium-hydroxide, cardiac agents, quinine, thiazides, calcium channel blockers, statins, urinary antispasmodics, glucosamine, NSAIDs, opioids and ophthalmologicals. SWS were lower in participants with ophthalmological disorders using ophthalmologicals (especially antiglaucoma agents and miotics), but also in those taking antidepressants, cardiac agents (mostly digitalis glycosides) and calcium channel blockers. Cardiovascular diseases and intake of anti-thrombotics (mainly low dose aspirins), calcium channel blockers and oral antidiabetics were associated with low LS. In older people, low salivary flow rates are associated with specific and high number of diseases and medications, but neither with age and gender per se nor with tobacco and alcohol consumption. Low UWS are associated with more diseases and medications than SWS and LS, which were primarily associated with cardiovascular diseases and medications including preventive agents such as low-dose aspirins and statins. New insights into medications and their association with salivary gland function were achieved using the ATC classification system. © 2010 John Wiley & Sons A/S.

Both glucocentric and cardiocentric approaches are necessary for a resilient disease such as diabetes.

PubMed

Caramelli, Bruno; Gualandro, Danielle Menosi

2018-03-01

Diabetes mellitus (DM) is a complex disease that compromises almost all systems in the human organism. Independently of the intrinsic mechanisms, the source of all consequences of DM is hyperglycemia, a condition associated to intense metabolic changes that will lead to increased morbidity and mortality in the long term. Several different therapeutic hypoglycemic oral agents were developed and significantly facilitated the treatment of hyperglycemia acting at different sites, since patients could take more than one agent. This glucocentric approach was somehow criticized as those hypoglycemic drugs have shown weaker than expected benefits in terms of cardiovascular outcomes and there was a sub use of statins and antihypertensive agents in this population. On the other hand, the catastrophic cardiovascular consequences of hypoglycemia in older adults submitted to tight glycemic control and the results of recent clinical trials that showed impressive reduction in cardiovascular outcomes with less potent antidiabetic agents seem to pave the way to a cardiocentric approach including a lax treatment of DM. Interestingly, the results obtained in recent studies with SGLT2 inhibitors are being mostly attributed to mechanisms other than its hypoglycemic effect in spite of including patients at high cardiovascular risk already taking hypoglycemic agents. Considering the worldwide growing number of patients with diabetes, caregivers must follow a dialectical thinking and choose a synthesis approach where glycemic control is the first and foremost target to be achieved, followed by control of cardiovascular risk factors.

Glucose-dependent and Glucose-sensitizing Insulinotropic Effect of Nateglinide: Comparison to Sulfonylureas and Repaglinide

PubMed Central

Wang, Shuya; Dunning, Beth E.

2001-01-01

Nateglinide, a novel D-phenylalanine derivative, stimulates insulin release via closure of KATP channels in pancreatic β-cell, a primary mechanism of action it shares with sulfonylureas (SUs) and repaglinide. This study investigated (1) the influence of ambient glucose levels on the insulinotropic effects of nateglinide, glyburide and repaglinide, and (2) the influence of the antidiabetic agents on glucose-stimulated insulin secretion (GSIS) in vitro from isolated rat islets. The EC50 of nateglinide to stimulate insulin secretion was 14 μM in the presence of 3mM glucose and was reduced by 6-fold in 8mM glucose and by 16-fold in 16mM glucose, indicating a glucose-dependent insulinotropic effect. The actions of glyburide and repaglinide failed to demonstrate such a glucose concentration-dependent sensitization. When tested at fixed and equipotent concentrations (~2x EC50 in the presence of 8mM glucose) nateglinide and repaglinide shifted the EC50s for GSIS to the left by 1.7mM suggesting an enhancement of islet glucose sensitivity, while glimepiride and glyburide caused, respectively, no change and a right shift of the EC50. These data demonstrate that despite a common basic mechanism of action, the insulinotropic effects of different agents can be influenced differentially by ambient glucose and can differentially influence the islet responsiveness to glucose. Further, the present findings suggest that nateglinide may exert a more physiologic effect on insulin secretion than comparator agents and thereby have less propensity to elicit hypoglycemia in vivo. PMID:12369728

Incretin-based therapy in type 2 diabetes: An evidence based systematic review and meta-analysis.

PubMed

Waldrop, Greer; Zhong, Jixin; Peters, Matthew; Goud, Aditya; Chen, Yin-Hsiu; Davis, Stephen N; Mukherjee, Bhramar; Rajagopalan, Sanjay

2018-01-01

Incretin based therapies such as dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1Ra) are increasingly used for the treatment of Type 2 diabetes mellitus. In clinical practice and in previously performed clinical trials, these agents are often used in combination with other oral anti-diabetic agents (OADs) and Insulin. Prior meta-analytic reviews however do not adequately address the impact of background therapy and active comparator arms. Accordingly, we aimed to further investigate the efficacy of incretin based therapies by updating existing reviews by including clinical trial evidence after 2008; estimating the pooled effect of incretin therapies on glycemic efficacy and weight-loss, stratified by comparator therapy (placebo, mono-therapy, etc.), estimating the impact of background OADs and within class (GLP-1Ra or DPP-4i) comparative efficacy, on glycemia control. 82 randomized controlled trials after 2008 with glycemic control and weight loss as primary end-points were included. Both DPP-4i and GLP-1Ra reduced HbA1c, but only GLP-1Ra caused weight loss when compared to either active comparator drugs or placebo. GLP-1Ra were more effective than DPP-4i in glycemia lowering. Long acting GLP-1Ra were more effective in HbA1c lowering than short-acting agents but with similar weight loss effect. The effect of DPP-4i incretin glycemic efficacy was not modified by background therapy used in the study. Copyright © 2016. Published by Elsevier Inc.

Abolishing coinsurance for oral antihyperglycemic agents: effects on social insurance budgets.

PubMed

Athanasakis, Kostas; Skroumpelos, Anastasis G; Tsiantou, Vassiliki; Milona, Katerina; Kyriopoulos, John

2011-02-01

To assess the effects of abolishing coinsurance for oral antihyperglycemic agents (OAAs) on the social insurance fund budget in Greece. A mathematical model estimating the effect of a decrease in patient coinsurance rate on demand for and adherence to OAAs and the subsequent clinical and economic outcomes. Price elasticity of demand for antidiabetic agents was used to estimate quantity demand change as a result of a coinsurance rate decrease and consequent increased adherence to OAAs. Given the inverse relationship between OAA adherence and glycated hemoglobin (A1C) level, the model calculated the mean decrease in A1C level and associated cost savings based on the cost difference between patients with controlled versus uncontrolled A1C levels. A decrease in patient coinsurance rate from 25% to 0% led to an incremental increase in OAA adherence of 30.5% and a mean decrease in A1C level of 0.6%. The A1C level decrease contributed to an 18.5% "shift" of uncontrolled patients to controlled A1C levels (<7%), which in economic terms translated into savings of 324 euro per patient over a 3-year period and an investment return rate of 122.8%. A series of 1-way and 2-way sensitivity analyses were conducted to verify the robustness and validity of the outcomes. The introduction of policies aimed at abolishing coinsurance for OAAs can result in improved patient outcomes and cost savings for the healthcare system.

The metabolic perturbators metformin, phenformin and AICAR interfere with the growth and survival of murine PTEN-deficient T cell lymphomas and human T-ALL/T-LL cancer cells.

PubMed

Rosilio, Célia; Lounnas, Nadia; Nebout, Marielle; Imbert, Véronique; Hagenbeek, Thijs; Spits, Hergen; Asnafi, Vahid; Pontier-Bres, Rodolphe; Reverso, Julie; Michiels, Jean-François; Sahra, Issam Ben; Bost, Fréderic; Peyron, Jean-François

2013-08-09

We show here that the antidiabetic agents metformin and phenformin and the AMPK activator AICAR exert strong anti-tumoural effects on tPTEN-/- lymphoma cells and on human T-ALL cell lines and primary samples. The compounds act by inhibiting tumour metabolism and proliferation and by inducing apoptosis in parallel with an activation of AMPK and an inhibition of constitutive mTOR. In tPTEN-/- cells, the drugs potentiated the anti-leukaemic effects of dexamethasone, and metformin and phenformin synergised with 2-deoxyglucose (2DG) to impair tumour cell survival. In vivo, metformin and AICAR strongly decreased the growth of luciferase-expressing tPTEN-/- cells xenografted in Nude mice, demonstrating that metabolism targeting could be a potent adjuvant strategy for lymphoma/leukaemia treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Diabetes and Ramadan: A concise and practical update

PubMed Central

Ahmed, Mohamed H.; Husain, Nazik Elmalaika; Elmadhoun, Wadie M.; Noor, Sufian K.; Khalil, Abbas A.; Almobarak, Ahmed O.

2017-01-01

Despite the fact that the month of Ramadan includes 29–30 days and the duration of fasting for each day can last for between 12 and 16 h, it was estimated that a large number of individuals with diabetes do fast during Ramadan. In light of recent advancement of new pharmacological agents, drugs such as vildagliptin, sitagliptin, and liraglutide were found to be safe to use during this month of fasting. These therapeutic agents can also be used in combination with metformin. The use of sulfonylureas, in most of the recent guidelines about diabetes and Ramadan, seems not to gain much support due to the risk of hypoglycemia. In this review, we also addressed the use of insulin injection, insulin pump, and education before, during, and after Ramadan. Further research is needed to determine (i) the therapeutic benefit of new antidiabetic agents and (ii) the benefit of new technologies for the treatment of diabetes. PMID:29026740

Next generation sequencing and de novo transcriptome analysis of Costus pictus D. Don, a non-model plant with potent anti-diabetic properties

PubMed Central

2012-01-01

Background Phyto-remedies for diabetic control are popular among patients with Type II Diabetes mellitus (DM), in addition to other diabetic control measures. A number of plant species are known to possess diabetic control properties. Costus pictus D. Don is popularly known as “Insulin Plant” in Southern India whose leaves have been reported to increase insulin pools in blood plasma. Next Generation Sequencing is employed as a powerful tool for identifying molecular signatures in the transcriptome related to physiological functions of plant tissues. We sequenced the leaf transcriptome of C. pictus using Illumina reversible dye terminator sequencing technology and used combination of bioinformatics tools for identifying transcripts related to anti-diabetic properties of C. pictus. Results A total of 55,006 transcripts were identified, of which 69.15% transcripts could be annotated. We identified transcripts related to pathways of bixin biosynthesis and geraniol and geranial biosynthesis as major transcripts from the class of isoprenoid secondary metabolites and validated the presence of putative norbixin methyltransferase, a precursor of Bixin. The transcripts encoding these terpenoids are known to be Peroxisome Proliferator-Activated Receptor (PPAR) agonists and anti-glycation agents. Sequential extraction and High Performance Liquid Chromatography (HPLC) confirmed the presence of bixin in C. pictus methanolic extracts. Another significant transcript identified in relation to anti-diabetic, anti-obesity and immuno-modulation is of Abscisic Acid biosynthetic pathway. We also report many other transcripts for the biosynthesis of antitumor, anti-oxidant and antimicrobial metabolites of C. pictus leaves. Conclusion Solid molecular signatures (transcripts related to bixin, abscisic acid, and geranial and geraniol biosynthesis) for the anti-diabetic properties of C. pictus leaves and vital clues related to the other phytochemical functions like antitumor, anti-oxidant, immuno-modulatory, anti-microbial and anti-malarial properties through the secondary metabolite pathway annotations are reported. The data provided will be of immense help to researchers working in the treatment of DM using herbal therapies. PMID:23176672

In Vitro Screening of Three Indian Medicinal Plants for Their Phytochemicals, Anticholinesterase, Antiglucosidase, Antioxidant, and Neuroprotective Effects.

PubMed

Penumala, Mohan; Zinka, Raveendra Babu; Shaik, Jeelan Basha; Amooru Gangaiah, Damu

2017-01-01

Cooccurrence of Diabetes Mellitus and Alzheimer's disease in elder people prompts scientists to develop multitarget agents that combat causes and symptoms of both diseases simultaneously. In line with this modern paradigm and as a follow-up to our previous studies, the present study is designed to investigate the crude methanolic extracts and subsequent CHCl 3 , n -BuOH, and H 2 O fractions of Acalypha alnifolia , Pavetta indica, and Ochna obtusata for their inhibitory activities towards specific targets involved in AD and DM, namely, acetylcholinesterase, butyrylcholinesterase, and α -glucosidase ( α -Glc). The methanolic extract and its derived chloroform fractions exhibited remarkable inhibitory capacities with IC 50 values being found at the μ g/mL level. Further studies on most active chloroform fractions presented a prominent ability to scavenge DPPH and ABTS reactive species and highest neuroprotective effect against H 2 O 2 induced cell injury. Phytochemical analysis showed a large amount of phenolics, flavonoids, and terpenoids in active fractions. In conclusion, A. alnifolia , P. indica, and O. obtusata could be promising sources for the treatment of AD and DM since these fractions induced significant anticholinesterase, antidiabetic, antioxidant, and neuroprotection effects attributable to phenolic, flavonoid, and terpenoid contents and encourage further studies for development of multifunctional therapeutic agent for AD and DM dual therapy.

Rosmarinic Acid Activates AMPK to Inhibit Metastasis of Colorectal Cancer

PubMed Central

Han, Yo-Han; Kee, Ji-Ye; Hong, Seung-Heon

2018-01-01

Rosmarinic acid (RA) has been used as an anti-inflammatory, anti-diabetic, and anti-cancer agent. Although RA has also been shown to exert an anti-metastatic effect, the mechanism of this effect has not been reported to be associated with AMP-activated protein kinase (AMPK). The aim of this study was to elucidate whether RA could inhibit the metastatic properties of colorectal cancer (CRC) cells via the phosphorylation of AMPK. RA inhibited the proliferation of CRC cells through the induction of cell cycle arrest and apoptosis. In several metastatic phenotypes of CRC cells, RA regulated epithelial–mesenchymal transition (EMT) through the upregulation of an epithelial marker, E-cadherin, and the downregulation of the mesenchymal markers, N-cadherin, snail, twist, vimentin, and slug. Invasion and migration of CRC cells were inhibited and expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were decreased by RA treatment. Adhesion and adhesion molecules such as ICAM-1 and integrin β1 expressions were also reduced by RA treatment. In particular, the effects of RA on EMT and MMPs expressions were due to the activation of AMPK. Moreover, RA inhibited lung metastasis of CRC cells by activating AMPK in mouse model. Collectively, these results proved that RA could be potential therapeutic agent against metastasis of CRC. PMID:29459827

Melatonin as a Pleiotropic Molecule with Therapeutic Potential for Type 2 Diabetes and Cancer.

PubMed

Wojcik, Marzena; Krawczyk, Michal; Wojcik, Pawel; Cypryk, Katarzyna; Wozniak, Lucyna Alicja

2017-11-20

The incidence of both type 2 diabetes (T2DM) and cancer is increasing worldwide, making these diseases a global health problem along with increasing healthcare expenditures. The current therapeutic approaches for treating these multifactorial diseases are far from satisfactory. As increasing evidence shows beneficial effects of melatonin (MLT) on typical pathological changes occurring during the development of T2DM and cancer, the present review focuses on molecular aspects of antidiabetic and anticancer activities of MLT and, moreover, discusses several future directions of research regarding MLT application as potential therapeutic agent. Critical literature analysis in PubMed central combined with personal expertise. Numerous in vitro and in vivo studies have revealed that MLT possesses a number of antidiabetic health benefits by diminishing hyperglycemia, insulin resistance, oxidative stress, and inflammation through modulating various intracellular signaling pathways or other targets involved in the pathophysiology of this disease. Mounting evidence also indicates that MLT exhibits multi-targeted anticancer effects in numerous human malignancies, mainly resulting from its ability to modulate several signal transduction pathways associated with cell survival, proliferation, and apoptosis. Furthermore, beneficial synergistic action of MLT with chemotherapy and radiotherapy has also been observed. Importantly, no adverse outcomes have been found from the clinical use of MLT, which highlights its therapeutic usefulness, either alone or in combination with other conventional therapies, in cancer treatment. The findings described in this review suggest that MLT may confer potential benefits to human health, particularly in respect to T2DM and cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pancreatoprotective effects of Geniotrigona thoracica stingless bee honey in streptozotocin-nicotinamide-induced male diabetic rats.

PubMed

Aziz, Muhammad Shakir Abdul; Giribabu, Nelli; Rao, Pasupuleti Visweswara; Salleh, Naguib

2017-05-01

Stingless bee honey (SLBH) has been claimed to possess multiple health benefits. Its anti-diabetic properties are however unknown. In this study, ability of SLBH from Geniotrigona thoracica stingless bee species in ameliorating pancreatic damage and in maintaining metabolic profiles were investigated in diabetic condition. SLBH at 1 and 2g/kg/b.w. was given orally to streptozotocin (STZ)-nicotinamide-induced male diabetic rats for 28days. Metabolic parameters (fasting blood glucose-FBG and lipid profiles-LP and serum insulin) were measured by biochemical assays. Distribution and expression level of insulin, oxidative stress marker i.e. catalase, inflammatory markers i.e. IKK-β, TNF-α, IL-1β and apoptosis marker i.e. caspase-9 in the pancreatic islets were identified and quantified respectively by immunohistochemistry. Levels of NF-κβ in pancreas were determined by enzyme-linked immunoassay (ELISA). SLBH administration to diabetic male rats prevented increase in FBG, total cholesterols (TC), triglyceride (TG) and low density lipoprotein (LDL) levels. However, high density lipoprotein (HDL) and serum insulin levels in diabetic rats receiving SLBH increased. Additionally, histopathological changes and expression level of oxidative stress, inflammation and apoptosis markers in pancreatic islets of diabetic rats decreased with increased expression level of insulin in the islets. LC-MS analysis revealed the presence of several compounds in SLBH that might be responsible for these effects. SLBH has great potential to be used as agent to protect the pancreas against damage and dysfunction where these could account for its anti-diabetic properties. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors from Natural Products: Discovery of Next-Generation Antihyperglycemic Agents.

PubMed

Choi, Chang-Ik

2016-08-27

Diabetes mellitus is a chronic condition associated with the metabolic impairment of insulin actions, leading to the development of life-threatening complications. Although many kinds of oral antihyperglycemic agents with different therapeutic mechanisms have been marketed, their undesirable adverse effects, such as hypoglycemia, weight gain, and hepato-renal toxicity, have increased demand for the discovery of novel, safer antidiabetic drugs. Since the important roles of the sodium-glucose cotransporter 2 (SGLT2) for glucose homeostasis in the kidney were recently elucidated, pharmacological inhibition of SGLT2 has been considered a promising therapeutic target for the treatment of type 2 diabetes. Since the discovery of the first natural SGLT2 inhibitor, phlorizin, several synthetic glucoside analogs have been developed and introduced into the market. Furthermore, many efforts to find new active constituents with SGLT2 inhibition from natural products are still ongoing. This review introduces the history of research on the development of early-generation SGLT2 inhibitors, and recent progress on the discovery of novel candidates for SGLT2 inhibitor from several natural products that are widely used in traditional herbal medicine.

Endothelial progenitor cells (EPCs) in ageing and age-related diseases: How currently available treatment modalities affect EPC biology, atherosclerosis, and cardiovascular outcomes.

PubMed

Altabas, Velimir; Altabas, Karmela; Kirigin, Lora

2016-10-01

Endothelial progenitor cells (EPCs) are mononuclear cells that circulate in the blood and are derived from different tissues, expressing cell surface markers that are similar to mature endothelial cells. The discovery of EPCs has lead to new insights in vascular repair and atherosclerosis and also a new theory for ageing. EPCs from the bone marrow and some other organs aid in vascular repair by migrating to distant vessels where they differentiate into mature endothelial cells and replace old and injured endothelial cells. The ability of EPCs to repair vascular damage depends on their number and functionality. Currently marketed drugs used in a variety of diseases can modulate these characteristics. In this review, the effect of currently available treatment options for cardiovascular and metabolic disorders on EPC biology will be discussed. The various EPC-based therapies that will be discussed include lipid-lowering agents, antihypertensive agents, antidiabetic drugs, phosphodiesteraze inhibitors, hormones, as well as EPC capturing stents. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Sodium-Glucose Cotransporter 2 Inhibitor Dapagliflozin Prevents Renal and Liver Disease in Western Diet Induced Obesity Mice

PubMed Central

Wang, Dong; Luo, Yuhuan; Wang, Xiaoxin; Orlicky, David J.; Myakala, Komuraiah; Yang, Pengyuan; Levi, Moshe

2018-01-01

Obesity and obesity related kidney and liver disease have become more prevalent over the past few decades, especially in the western world. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with promising effects on cardiovascular and renal function. Given SGLT2 inhibitors exert both anti-diabetic and anti-obesity effects by promoting urinary excretion of glucose and subsequent caloric loss, we investigated the effect of the highly selective renal SGLT2 inhibitor dapagliflozin in mice with Western diet (WD) induced obesity. Low fat (LF) diet or WD-fed male C57BL/6J mice were treated with dapagliflozin for 26 weeks. Dapagliflozin attenuated the WD-mediated increases in body weight, plasma glucose and plasma triglycerides. Treatment with dapagliflozin prevented podocyte injury, glomerular pathology and renal fibrosis determined by second harmonic generation (SHG), nephrin, synaptopodin, collagen IV, and fibronectin immunofluorescence microscopy. Oil Red O staining showed dapagliflozin also decreased renal lipid accumulation associated with decreased SREBP-1c mRNA abundance. Moreover, renal inflammation and oxidative stress were lower in the dapagliflozin-treated WD-fed mice than in the untreated WD-fed mice. In addition, dapagliflozin decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic lipid accumulation as determined by H&E and Oil Red O staining, and Coherent Anti-Stokes Raman Scattering (CARS) microscopy, and hepatic fibrosis as determined by picrosirius red (PSR) staining and TPE-SHG microscopy in WD-fed mice. Thus, our study demonstrated that the co-administration of the SGLT2 inhibitor dapagliflozin attenuates renal and liver disease during WD feeding of mice. PMID:29301371

The Sodium-Glucose Cotransporter 2 Inhibitor Dapagliflozin Prevents Renal and Liver Disease in Western Diet Induced Obesity Mice.

PubMed

Wang, Dong; Luo, Yuhuan; Wang, Xiaoxin; Orlicky, David J; Myakala, Komuraiah; Yang, Pengyuan; Levi, Moshe

2018-01-03

Obesity and obesity related kidney and liver disease have become more prevalent over the past few decades, especially in the western world. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with promising effects on cardiovascular and renal function. Given SGLT2 inhibitors exert both anti-diabetic and anti-obesity effects by promoting urinary excretion of glucose and subsequent caloric loss, we investigated the effect of the highly selective renal SGLT2 inhibitor dapagliflozin in mice with Western diet (WD) induced obesity. Low fat (LF) diet or WD-fed male C57BL/6J mice were treated with dapagliflozin for 26 weeks. Dapagliflozin attenuated the WD-mediated increases in body weight, plasma glucose and plasma triglycerides. Treatment with dapagliflozin prevented podocyte injury, glomerular pathology and renal fibrosis determined by second harmonic generation (SHG), nephrin, synaptopodin, collagen IV, and fibronectin immunofluorescence microscopy. Oil Red O staining showed dapagliflozin also decreased renal lipid accumulation associated with decreased SREBP-1c mRNA abundance. Moreover, renal inflammation and oxidative stress were lower in the dapagliflozin-treated WD-fed mice than in the untreated WD-fed mice. In addition, dapagliflozin decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic lipid accumulation as determined by H&E and Oil Red O staining, and Coherent Anti-Stokes Raman Scattering (CARS) microscopy, and hepatic fibrosis as determined by picrosirius red (PSR) staining and TPE-SHG microscopy in WD-fed mice. Thus, our study demonstrated that the co-administration of the SGLT2 inhibitor dapagliflozin attenuates renal and liver disease during WD feeding of mice.

Plants used as antidiabetics in popular medicine in Rio Grande do Sul, southern Brazil.

PubMed

Trojan-Rodrigues, M; Alves, T L S; Soares, G L G; Ritter, M R

2012-01-06

Plants are widely as antidiabetics. The study of these plants is essential because many of them may have undesirable effects, such as acute or chronic toxicity; or their use may even delay or discourage the adoption of the proper and effective treatment. The present study surveyed the plant species that are popularly used to treat diabetes mellitus in the state of Rio Grande do Sul in southern Brazil. Sixteen ethnobotanical surveys performed in the state were consulted, and the species used to treat diabetes were listed. For species cited in at least two of the studies, scientific data related to antidiabetic activity were searched in the ISI Knowledge database. The scientific binomial of each species was used as keywords, and data found in review papers were also included. A total of 81 species in 42 families were mentioned; the most important families were Asteraceae and Myrtaceae. Twenty eight species were cited at least twice as being used to treat diabetes in the state. For 11 of these, no scientific data regarding antidiabetic activity could be located. The species most frequently mentioned for use with diabetes were Syzygium cumini (Myrtaceae) and Bauhinia forficata (Fabaceae), in 12 studies each, followed by Sphagneticola trilobata (Asteraceae), in six studies; and Baccharis trimera (Asteraceae), Bidens pilosa (Asteraceae), Cynara scolymus (Asteraceae), and Leandra australis (Melastomataceae) in four studies each. Bauhinia forficata and Syzygium cumini have been studied in more detail for antidiabetic activity. A considerable number of plant species are traditionally used for the treatment of diabetes melitus in the Rio Grande do Sul State. The majority of those plants that have been studied for antidiabetic activity showed promising results, mainly for Bauhinia forficata and Syzygium cumini. However, for most of the plants mentioned, the studies are not sufficient to guarantee the efficacy and safety in the use of these plants in the treatment against diabetes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Metabolomics Study of Type 2 Diabetes Mellitus and the AntiDiabetic Effect of Berberine in Zucker Diabetic Fatty Rats Using Uplc-ESI-Hdms.

PubMed

Dong, Yu; Chen, Yi-Tao; Yang, Yuan-Xiao; Zhou, Xiao-Jie; Dai, Shi-Jie; Tong, Jun-Feng; Shou, Dan; Li, Changyu

2016-05-01

The present study aimed to evaluate the pathogenesis of type 2 diabetes mellitus (T2DM) and the anti-diabetic effect of berberine in Zucker diabetic fatty (ZDF) rats. A urinary metabolomics analysis was performed with ultra-performance liquid chromatography/electrospray ionization synapt high-definition mass spectrometry. Pattern recognition approaches were integrated to discover differentiating metabolites. We identified 29 ions (13 in negative mode and 16 in positive mode) as 'differentiating metabolites' with this metabolomic approach. A functional pathway analysis revealed that the alterations were mainly associated with glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions and sphingolipid metabolism. These results indicated that the dysfunctions of glycometabolism and lipometabolism are involved in the pathological process of T2DM. Berberine could decrease the serum levels of glycosylated hemoglobin, total cholesterol and triglyceride and increase the secretion of insulin. The urinary metabolomics analysis showed that berberine could reduce the concentrations of citric acid, tetrahydrocortisol, ribothymidine and sphinganine to a near-normal state. These results suggested that the anti-diabetic effect of berberine occurred mainly via its regulation of glycometabolism and lipometabolism and activation of adenosine 5'-monophosphate-activated protein kinase. Our work not only provides a better understanding of the anti-diabetic effect of berberine in ZDF rats but also supplies a useful database for further study in humans and for investigating the pharmacological actions of drugs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Antidiabetic Activity of Polyherbal Formulation in Streptozotocin – Nicotinamide Induced Diabetic Wistar Rats

PubMed Central

Petchi, Rajendran Ramesh; Vijaya, Chockalingam; Parasuraman, Subramani

2014-01-01

Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known plants available throughout India and they are commonly used for the treatment of various diseases including diabetes mellitus. The antidiabetic activity of the individual plant parts is well known, but the synergistic or combined effects are unclear. The concept of polyherbalism has been highlighted in Sharangdhar Samhita, an Ayurvedic literature dating back to 1300 AD. Polyherbal formulations enhance the therapeutic action and reduce the concentrations of single herbs, thereby reducing adverse events. The aim of the present study is to formulate a polyherbal formulation and evaluate its antidiabetic potential in animals. The polyherbal formulation was formulated using the ethanol extracts of the stem bark of G. pentaphylla, whole plant of T. procumbens, and leaves of M. indica. The polyherbal formulation contains the ethanol extracts of G. pentaphylla, T. procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished product was evaluated as per the World Health Organization's guidelines for the quality control of herbal materials. The quality testing parameters of the polyherbal formulation were within the limits. Fingerprint analysis of the polyherbal formulation showed effective separation at 366 nm, and it revealed that the active compound present in the polyherbal formulation and the active compounds present in all the three extracts were the same. The acute toxicity studies of the polyherbal formulation did not show any toxic symptoms in doses up to 2000 mg/kg over 14 days. The oral antidiabetic activity of the polyherbal formulation (250 and 500 mg/kg) was screened against streptozotocin (50 mg/kg; i.p.) + nicotinamide (120 mg/kg; i.p.) induced diabetes mellitus in rats. The investigational drug was administered for 21 consecutive days, and the effect of the polyherbal formulation on blood glucose levels was studied at regular intervals. At the end of the study, the blood samples were collected from all the animals for biochemical estimation, and the animals were sacrificed and the liver and pancreatic tissues were collected for histopathologic analysis. Polyherbal formulation showed significant antidiabetic activity at 250 and 500 mg/kg, respectively, and this effect was comparable with that of glibenclamide. The antidiabetic activity of polyherbal formulation is supported by biochemical and histopathologic analysis. PMID:24860734

Antidiabetic activity of polyherbal formulation in streptozotocin - nicotinamide induced diabetic wistar rats.

PubMed

Petchi, Rajendran Ramesh; Vijaya, Chockalingam; Parasuraman, Subramani

2014-04-01

Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known plants available throughout India and they are commonly used for the treatment of various diseases including diabetes mellitus. The antidiabetic activity of the individual plant parts is well known, but the synergistic or combined effects are unclear. The concept of polyherbalism has been highlighted in Sharangdhar Samhita, an Ayurvedic literature dating back to 1300 AD. Polyherbal formulations enhance the therapeutic action and reduce the concentrations of single herbs, thereby reducing adverse events. The aim of the present study is to formulate a polyherbal formulation and evaluate its antidiabetic potential in animals. The polyherbal formulation was formulated using the ethanol extracts of the stem bark of G. pentaphylla, whole plant of T. procumbens, and leaves of M. indica. The polyherbal formulation contains the ethanol extracts of G. pentaphylla, T. procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished product was evaluated as per the World Health Organization's guidelines for the quality control of herbal materials. The quality testing parameters of the polyherbal formulation were within the limits. Fingerprint analysis of the polyherbal formulation showed effective separation at 366 nm, and it revealed that the active compound present in the polyherbal formulation and the active compounds present in all the three extracts were the same. The acute toxicity studies of the polyherbal formulation did not show any toxic symptoms in doses up to 2000 mg/kg over 14 days. The oral antidiabetic activity of the polyherbal formulation (250 and 500 mg/kg) was screened against streptozotocin (50 mg/kg; i.p.) + nicotinamide (120 mg/kg; i.p.) induced diabetes mellitus in rats. The investigational drug was administered for 21 consecutive days, and the effect of the polyherbal formulation on blood glucose levels was studied at regular intervals. At the end of the study, the blood samples were collected from all the animals for biochemical estimation, and the animals were sacrificed and the liver and pancreatic tissues were collected for histopathologic analysis. Polyherbal formulation showed significant antidiabetic activity at 250 and 500 mg/kg, respectively, and this effect was comparable with that of glibenclamide. The antidiabetic activity of polyherbal formulation is supported by biochemical and histopathologic analysis.

Antidiabetic potential: in vitro inhibition effects of some natural phenolic compounds on α-glycosidase and α-amylase enzymes.

PubMed

Taslimi, Parham; Gulçin, İlhami

2017-10-01

α-Glycosidase is a catalytic enzyme and it destroys the complex carbohydrates into simple absorbable sugar units. The natural phenolic compounds were tested for their antidiabetic properties as α-glycosidase and α-amylase inhibitors. The phenolic compounds investigated in this study have been used as antidiabetic common medicines. This paper aimed to consider their capability to inhibit α-amylase and α-glycosidase, two significant enzymes defined in serum glucose adjustment. These examination recorded impressive inhibition profiles with IC 50 values in the range of 137.36-737.23 nM against α-amylase and 29.01-157.96 nM against α-glycosidase. © 2017 Wiley Periodicals, Inc.

Anti-diabetic activity of a mineraloid isolate, in vitro and in genetically diabetic mice.

PubMed

Deneau, Joel; Ahmed, Taufeeq; Blotsky, Roger; Bojanowski, Krzysztof

2011-01-01

Type II diabetes is a metabolic disease mediated through multiple molecular pathways. Here, we report anti-diabetic effect of a standardized isolate from a fossil material - a mineraloid leonardite - in in vitro tests and in genetically diabetic mice. The mineraloid isolate stimulated mitochondrial metabolism in human fibroblasts and this stimulation correlated with enhanced expression of genes coding for mitochondrial proteins such as ATP synthases and ribosomal protein precursors, as measured by DNA microarrays. In the diabetic animal model, consumption of the Totala isolate resulted in decreased weight gain, blood glucose, and glycated hemoglobin. To our best knowledge, this is the first description ever of a fossil material having anti-diabetic activity in pre-clinical models.

Phytochemical distribution in hull and cotyledon of adzuki bean (Vigna angularis L.) and mung bean (Vigna radiate L.), and their contribution to antioxidant, anti-inflammatory and anti-diabetic activities.

PubMed

Luo, Jiaqiang; Cai, Weixi; Wu, Tong; Xu, Baojun

2016-06-15

Total saponin content, total phenolics content, total flavonoids content, condensed tannin content in hull, cotyledon and whole grain of both adzuki bean and mung bean were determined by colorimetric methods. Vitexin and isovitexin contents in mung bean were determined by HPLC. Antioxidant effects were evaluated with DPPH scavenging activity and ferric reducing antioxidant power assay. In vitro anti-inflammatory and anti-diabetic effects of beans were evaluated by protease and aldose reductase inhibitory assays, respectively. The results indicated that the bean hulls were the most abundant in phytochemicals and largely contributed antioxidant activities, anti-inflammatory effects and anti-diabetic effects of whole grains. The result showed that mung bean hull was the most abundant with vitexin at 37.43 mg/g and isovitexin at 47.18 mg/g, respectively. Most of the phytochemicals and bioactivities were most predominantly contributed by the bean hulls with exception for condensed tannin of mung bean; which was more abundant in the cotyledon than its hull. Copyright © 2016 Elsevier Ltd. All rights reserved.

The opposite effect of isotype-selective monoamine oxidase inhibitors on adipogenesis in human bone marrow mesenchymal stem cells.

PubMed

Byun, Youngjoo; Park, Jongho; Hong, Soo Hyun; Han, Mi Hwa; Park, Suzie; Jung, Hyo-Il; Noh, Minsoo

2013-06-01

Adiponectin production during adipocyte differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) can be used to evaluate the pharmacological activity of anti-diabetic drugs to improve insulin sensitivity. Monoamine oxidase (MAO) inhibitors such as phenelzine and pargyline inhibit adipogenesis in murine pre-adipocytes. In this study, however, we found that selective MAO-A inhibitors, moclobemide and Ro41-1049, and a selective MAO-B inhibitor, selegiline, promoted adiponectin production during adipocyte differentiation in hBM-MSCs, which suggested the anti-diabetic potential of these drugs. In contrast, non-selective MAO inhibitors, phenelzine and tranylcypromine, inhibited adipocyte differentiation of hBM-MSCs. Concomitant treatments of MAO-A and MAO-B selective inhibitors did not change the stimulatory effect on adiponectin production in hBM-MSCs. Taken together, the opposite effects of isotype-selective MAO inhibitors on adiponectin production during adipogenesis in hBM-MSCs may not be directly associated with the inhibitory effects of MAO, suggested that the structure of MAO inhibitors may contain a novel anti-diabetic pharmacophore. Copyright © 2013 Elsevier Ltd. All rights reserved.

Assessment of antidiabetic potential of Cynodon dactylon extract in streptozotocin diabetic rats.

PubMed

Singh, Santosh Kumar; Kesari, Achyut Narayan; Gupta, Rajesh Kumar; Jaiswal, Dolly; Watal, Geeta

2007-11-01

This study was undertaken to investigate the hypoglycemic and antidiabetic effect of single and repeated oral administration of the aqueous extract of Cynodon dactylon (Family: Poaceae) in normal and streptozotocin induced diabetic rats, respectively. The effect of repeated oral administration of aqueous extract on serum lipid profile in diabetic rats was also examined. A range of doses, viz. 250, 500 and 1000mg/kg bw of aqueous extract of Cynodon dactylon were evaluated and the dose of 500mg/kg was identified as the most effective dose. It lowers blood glucose level around 31% after 4h of administration in normal rats. The same dose of 500mg/kg produced a fall of 23% in blood glucose level within 1h during glucose tolerance test (GTT) of mild diabetic rats. This dose has almost similar effect as that of standard drug tolbutamide (250mg/kg bw). Severely diabetic rats were also treated daily with 500mg/kg bw for 14 days and a significant reduction of 59% was observed in fasting blood glucose level. A reduction in the urine sugar level and increase in body weight of severe diabetic rats were additional corroborating factors for its antidiabetic potential. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were decreased by 35, 77 and 29%, respectively, in severely diabetic rats whereas, cardioprotective, high density lipoprotein (HDL) was increased by 18%. These results clearly indicate that aqueous extract of Cynodon dactylon has high antidiabetic potential along with significant hypoglycemic and hypolipidemic effects.

Mechanisms for antidiabetic effect of gingerol in cultured cells and obese diabetic model mice.

PubMed

Son, Myoung Jin; Miura, Yutaka; Yagasaki, Kazumi

2015-08-01

There have been studies on health beneficial effects of ginger and its components. However, there still remain certain aspects that are not well defined in their anti-hyperglycemic effects. Our aims were to find evidence of possible mechanisms for antidiabetic action of [6]-gingerol, a pungent component of ginger, employing a rat skeletal muscle-derived cell line, a rat-derived pancreatic β-cell line, and type 2 diabetic model animals. The antidiabetic effect of [6]-gingerol was investigated through studies on glucose uptake in L6 myocytes and on pancreatic β-cell protective ability from reactive oxygen species (ROS) in RIN-5F cells. Its in vivo effect was also examined using obese diabetic db/db mice. [6]-Gingerol increased glucose uptake under insulin absent condition and induced 5' adenosine monophosphate-activated protein kinase phosphorylation in L6 myotubes. Promotion by [6]-gingerol of glucose transporter 4 (GLUT4) translocation to plasma membrane was visually demonstrated by immunocytochemistry in L6 myoblasts transfected with glut4 cDNA-coding vector. [6]-Gingerol suppressed advanced glycation end product-induced rise of ROS levels in RIN-5F pancreatic β-cells. [6]-Gingerol feeding suppressed the increases in fasting blood glucose levels and improved glucose intolerance in db/db mice. [6]-Gingerol regulated hepatic gene expression of enzymes related to glucose metabolism toward decreases in gluconeogenesis and glycogenolysis as well as an increase in glycogenesis, thereby contributing to reductions in hepatic glucose production and hence blood glucose concentrations. These in vitro and in vivo results strongly suggest that [6]-gingerol has antidiabetic potential through multiple mechanisms.

Antidiabetic and antihyperlipidemic effects of the stem of Musa sapientum Linn. in streptozotocin-induced diabetic rats.

PubMed

Dikshit, Piyush; Shukla, Kirtikar; Tyagi, Mool Kumar; Garg, Piyush; Gambhir, Jasvindar K; Shukla, Rimi

2012-12-01

Musa sapientum Linn. is a herbaceous plant of the Musaceae family. It has been used in India for the treatment of gastric ulcer, hypertension, diarrhea, dysentery, and diabetes. The antidiabetic effect of the fruit, root, and flower has been demonstrated. The aim of the present study was to assess the antidiabetic and antihyperlipidemic effects of the stem of M. sapientum Linn. Diabetes was induced in rats by streptozotocin injection (45 mg/kg, i.p.). Diabetic rats were treated for 2 weeks with different doses of lyophilized stem juice of M. sapientum Linn. (25, 50, and 100 mg/kg) to select the most effective dose. The effects of 4 weeks treatment with this dose (50 mg/kg) on fasting and postprandial plasma glucose (FPG, PPG) levels, body weight, lipid profile, HbA1c, insulin, liver enzymes (i.e. glucokinase, glucose-6-phosphatase and 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase) and muscle and liver glycogen were evaluated. The most effective dose of lyophilized stem juice of M. sapientum Linn. was 50 mg/kg. Four weeks treatment with this dose resulted in significant decreases in FPG and PPG (P < 0.05). Serum insulin increased (P < 0.05) whereas HbA1c decreased (P < 0.05). Diabetes-induced changes to the lipid profile, muscle and liver glycogen, and enzyme activity (i.e. glucokinase, glucose-6-phosphatase, and HMG-CoA reductase) were restored near to normal levels (P < 0.05). Diabetic rats responded favorably to treatment with lyophilized stem juice of M. sapientum Linn., which exhibits antidiabetic and antihyperlipidemic effects. © 2012 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Antidiabetic effect of Sida cordata in alloxan induced diabetic rats.

PubMed

Shah, Naseer Ali; Khan, Muhammad Rashid

2014-01-01

Medicinal plants are efficient ameliorator of oxidative stress associated with diabetes mellitus. In this study, ethyl acetate fraction (SCEE) of Sida cordata was investigated for scientific validation of its folk use in diabetes. Antidiabetic effect of SCEE was confirmed by antihyperglycemic activity in normal glucose loaded and diabetic glucose loaded animals as well as normal off feed animals. Confirmation of antidiabetic activity and toxicity ameliorative role of S. cordata was investigated in a chronic multiple dose treatment study of fifteen days. A single dose of alloxan (120 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides, and cholesterol and decreased the high-density lipoproteins. Concurrent with these changes, there was an increase in the concentration of lipid peroxidation (TBARS), H2O2, and nitrite in pancreas, liver, and testis. This oxidative stress was related to a decrease in glutathione content (GSH) and antioxidant enzymes. Administration of SCEE for 15 days after diabetes induction ameliorated hyperglycemia, restored lipid profile, blunted the increase in TBARS, H2O2, and nitrite content, and stimulated the GSH production in the organs of alloxan-treated rats. We suggested that SCEE could be used as antidiabetic component in case of diabetes mellitus. This may be related to its antioxidative properties.

Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota.

PubMed

Chang, Chih-Jung; Lin, Chuan-Sheng; Lu, Chia-Chen; Martel, Jan; Ko, Yun-Fei; Ojcius, David M; Tseng, Shun-Fu; Wu, Tsung-Ru; Chen, Yi-Yuan Margaret; Young, John D; Lai, Hsin-Chih

2015-06-23

Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis-as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels-but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further show that high molecular weight polysaccharides (>300 kDa) isolated from the WEGL extract produce similar anti-obesity and microbiota-modulating effects. Our results indicate that G. lucidum and its high molecular weight polysaccharides may be used as prebiotic agents to prevent gut dysbiosis and obesity-related metabolic disorders in obese individuals.

Disordered haematopoiesis and athero-thrombosis.

PubMed

Murphy, Andrew J; Tall, Alan R

2016-04-07

Atherosclerosis, the major underlying cause of cardiovascular disease, is characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries. Increased production and activation of monocytes, neutrophils, and platelets, driven by hypercholesterolaemia and defective high-density lipoproteins-mediated cholesterol efflux, tissue necrosis and cytokine production after myocardial infarction, or metabolic abnormalities associated with diabetes, contribute to atherogenesis and athero-thrombosis. This suggests that in addition to traditional approaches of low-density lipoproteins lowering and anti-platelet drugs, therapies directed at abnormal haematopoiesis, including anti-inflammatory agents, drugs that suppress myelopoiesis, and excessive platelet production, rHDL infusions and anti-obesity and anti-diabetic agents, may help to prevent athero-thrombosis. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, is a novel, selective and competitive dipeptidyl peptidase-IV inhibitor.

PubMed

Yasuda, Nobuyuki; Nagakura, Tadashi; Inoue, Takashi; Yamazaki, Kazuto; Katsutani, Naruo; Takenaka, Osamu; Clark, Richard; Matsuura, Fumiyoshi; Emori, Eita; Yoshikawa, Seiji; Kira, Kazunobu; Ikuta, Hironori; Okada, Toshimi; Saeki, Takao; Asano, Osamu; Tanaka, Isao

2006-10-24

Dipeptidyl peptidase IV (DPP-IV) inhibitors are expected to become a useful new class of anti-diabetic agent. The aim of the present study is to characterize the in vitro and in vivo profile of E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, which is a novel imidazopyridazinone-derived DPP-IV inhibitor. E3024 inhibited recombinant human and mouse DPP-IV with IC50 values of approximately 100 nM. E3024 inhibited DPP-IV in human, mouse, rat and canine plasma with IC50 values of 140 to 400 nM. In contrast, E3024 did not inhibit DPP-8 or DPP-9 activity. Kinetic analysis indicated that E3024 is a competitive DPP-IV inhibitor. In Zucker fa/fa rats, E3024 (1 mg/kg) reduced glucose excursion after glucose load, with increases in plasma insulin and active glucagon-like peptide-1 levels. In fasted rats, this compound did not cause hypoglycemia. In a rat 4-week toxicological study, no notable changes were found at doses up to 750 mg/kg. The present preclinical studies indicate that E3024 is a novel selective DPP-IV inhibitor with anti-diabetic effects and a good safety profile.

Selective Inhibition of PTP1B by Vitalboside A from Syzygium cumini Enhances Insulin Sensitivity and Attenuates Lipid Accumulation Via Partial Agonism to PPARγ: In Vitro and In Silico Investigation.

PubMed

Thiyagarajan, Gopal; Muthukumaran, Padmanaban; Sarath Kumar, Baskaran; Muthusamy, Velusamy Shanmuganathan; Lakshmi, Baddireddi Subhadra

2016-08-01

Although antidiabetic drugs show good insulin-sensitizing property for T2DM, they also exhibit undesirable side-effects. Partial peroxisome proliferator-activated receptor γ agonism with protein tyrosine phosphatase 1B inhibition is considered as an alternative therapeutic approach toward the development of a safe insulin sensitizer. Bioactivity-based fractionation and purification of Syzygium cumini seeds led to the isolation and identification of bifunctional Vitalboside A, which showed antidiabetic and anti-adipogenic activities, as measured by glucose uptake in L6 and 3T3-L1 adipocytes and Nile red assay. A non-competitive allosteric inhibition of protein tyrosine phosphatase 1B by Vitalboside A was observed, which was confirmed by docking studies. Inhibitor studies with wortmannin and genistein showed an IRTK- and PI3K-dependent glucose uptake. A PI3K/AKT-dependent activation of GLUT4 translocation and an inactivation of GSK3β were observed, confirming its insulin-sensitizing potential. Vitalboside A exhibited partial transactivation of peroxisome proliferator-activated receptor γ with an increase in adiponectin secretion, which was confirmed using docking analysis. Vitalboside A is a bifunctional molecule derived from edible plant showing inhibition of PTP1B and partial agonism to peroxisome proliferator-activated receptor γ which could be a promising therapeutic agent in the management of obesity and diabetes. © 2016 John Wiley & Sons A/S.

Recent development of single preparations and fixed-dose combination tablets for the treatment of non-insulin-dependent diabetes mellitus : A comprehensive summary for antidiabetic drugs.

PubMed

Li, Jianwen; Lian, He

2016-06-01

As a complex endocrine and metabolic disorder, type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus, NIDDM) has become a major threat to human health. Because of the heterogeneous and progressive disorders induced by insulin resistance and pancreatic b-cell dysfunction, the treatment of NIDDM is still challenging. Although antidiabetic drugs with different pharmacological mechanisms of action have been used clinically, different degrees of undesirable glucose control and the incidences of a variety of side effects, including hypoglycemia, cardiovascular complications and weight gain require the better treatment options. This article has overviewed the current literature about commercially available antidiabetic drugs with different pharmacological mechanisms of action in the treatment of NIDDM, and summarized the published data regarding the efficacy, tolerability, and safety of currently available single preparations and fixed-dose combinations, aiming to provide important information for the development and application of antidiabetic drugs in the future. The literature search from 1989 to 2015 was conducted by PubMed, ScienceDirect, Springer, American Diabetes Association, and U.S. FDA Drugs databases.

Potential of glyburide to reduce intracerebral edema in brain metastases.

PubMed

Boggs, Drexell Hunter; Simard, J Marc; Steven, Andrew; Mehta, Minesh P

2014-04-01

Metastatic disease to the brain results in significant morbidity because of edema in the central nervous system. Current anti-edema therapies are either expensive or result in unwanted long-term side effects. Sulfonylurea receptor 1 (Sur1) is a transmembrane protein that, when activated in the central nervous system, allows for unregulated sodium influx into cells, a process that has been linked to cytotoxic edema formation in ischemic stroke, subarachnoid hemorrhage, spinal cord injury, traumatic brain injury, and, most recently, brain metastases. In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema.

Orthosiphol A from the aerial parts of Orthosiphon aristatus is putatively responsible for hypoglycemic effect via alpha-glucosidase inhibition.

PubMed

Damsud, Thanakorn; Grace, Mary H; Adisakwattana, Sirichai; Phuwapraisirisan, Preecha

2014-05-01

An infusion of Orthosiphon aristatus has long been used for diabetes therapy; however, the active principles remained unknown. Herein, we report the identification of the putative agents responsible for this antidiabetic activity using an a-glucosidase-guided isolation. Four flavonoids named sinensetin (1), salvigenin (2), tetramethylscutellarein (3) and 3,7,4'-tri-O-methylkaempferol (4), together with a diterpenoid named orthosiphol A (5), were characterized, based on analysis of their spectroscopic data. Flavonoids 3 and 4 inhibited yeast a-glucosidase with IC,o values of 6.34 and 0.75 mM, respectively, whereas orthosiphol A (5) selectively inhibited intestinal maltase with an IC5o, value of 6.54 mM. A kinetic investigation of 5 indicated that it retarded maltase function in a noncompetitive manner.

Characteristics and in vitro Anti-diabetic Properties of the Korean Rice Wine, Makgeolli Fermented with Laminaria japonica.

PubMed

Choi, Jae-Suk; Seo, Hyo Ju; Lee, Yu-Ri; Kwon, Su-Jung; Moon, Sun Hwa; Park, Sun-Mee; Sohn, Jae Hak

2014-06-01

New in vitro anti-diabetes makgeolli was produced from rice by adding various quantities of Laminaria japonica, and the fermentation characteristics of the L. japonica makgeolli during the fermentation process were investigated. The contents of alcohol and reducing sugar, and viable count of yeast, of L. japonica makgeolli were not significantly changed when the proportion of L. japonica was increased. The total acid content decreased with an increase in L. japonica concentration; the pH and total bacterial cell count increased in proportion with the increase in L. japonica concentration. The L. japonica makgeolli contents of free sugars, such as fructose, glucose, and sucrose, and of organic acids, such as acetic acid, citric acid, succinic acid, and lactic acid, were altered during fermentation and showed various patterns. The effects of the quantity of L. japonica added on the acceptability and anti-diabetes activities of L. japonica makgeolli were also investigated. In a sensory evaluation, L. japonica makgeolli brewed by adding 2.5 or 5% L. japonica to the mash showed the best overall acceptability; the 12.5% L. japonica sample was least favored due to its seaweed flavor. L. japonica addition did not increase the peroxynitrite-scavenging activity of makgeolli. L. japonica makgeolli showed potent anti-diabetes activity, particularly that containing >7.5% L. japonica. Therefore, L. japonica makgeolli may represent a new functional makgeolli with anti-diabetes properties.

Anti-diabetic formulations of Nāga bhasma (lead calx): A brief review.

PubMed

Rajput, Dhirajsingh; Patgiri, B J; Galib, R; Prajapati, P K

2013-07-01

Ayurvedic formulations usually contain ingredients of herbal, mineral, metal or animal in origin. Nāga bhasma (lead calx) is a potent metallic formulation mainly indicated in the treatment of Prameha (~diabetes). Until date, no published information is available in compiled form on the formulations containing Nāga bhasma as an ingredient, their dose and indications. Therefore, in the present study, an attempt has been made to compile various formulations of Nāga bhasma indicated in treating Prameha. The present work aims to collect information on various formulations of Nāga bhasma mainly indicated in treating Prameha and to elaborate the safety and efficacy of Nāga bhasma as a Pramehaghna (antidiabetic) drug. Critical review of formulations of Nāga bhasma is compiled from various Ayurvedic texts and the therapeutic efficacy of Nāga bhasma is discussed on the basis of available data. Antidiabetic formulations of Nāga bhasma were discovered around 12(th) century CE. There are 44 formulations of Nāga bhasma mainly indicated for Prameha. Haridrā (Curcuma longa Linn), Āmalakī (Emblica officinalis), Guḍūci (Tinospora cordifolia) and Madhu (honey) enhance the antidiabetic action of Nāga bhasma and also help to prevent diabetic complications as well as any untoward effects of Nāga bhasma. On the basis of the reviewed research, it is concluded that Nāga bhasma possesses significant antidiabetic property.

Enzyme inhibitory and radical scavenging effects of some antidiabetic plants of Turkey.

PubMed

Orhan, Nilüfer; Hoçbaç, Sanem; Orhan, Didem Deliorman; Asian, Mustafa; Ergun, Fatma

2014-06-01

Ethnopharmacological field surveys demonstrated that many plants, such as Gentiana olivieri, Helichrysum graveolens, Helichrysum plicatum ssp. plicatum, Juniperus oxycedrus ssp. oxycedrus, Juniperus communis var. saxatilis, Viscum album (ssp. album, ssp. austriacum), are used as traditional medicine for diabetes in different regions of Anatolia. The present study was designed to evaluate the in vitro antidiabetic effects of some selected plants, tested in animal models recently. α-glucosidase and α-amylase enzyme inhibitory effects of the plant extracts were investigated and Acarbose was used as a reference drug. Additionally, radical scavenging capacities were determined using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) ABTS radical cation scavenging assay and total phenolic content of the extracts were evaluated using Folin Ciocalteu method. H. graveolens ethanol extract exhibited the highest inhibitory activity (55.7 % ± 2.2) on α-amylase enzyme. Additionally, J. oxycedrus hydro-alcoholic leaf extract had potent α-amylase inhibitory effect, while the hydro-alcoholic extract of J. communis fruit showed the highest α-glucosidase inhibitory activity (IC50: 4.4 μg/ml). Results indicated that, antidiabetic effect of hydro-alcoholic extracts of H. graveolens capitulums, J. communis fruit and J. oxycedrus leaf might arise from inhibition of digestive enzymes.

Zinc dependent Histone deacetylase inhibitors in cancer therapeutics: Recent update.

PubMed

Georgianos, Panagiotis I; Divani, Maria; Eleftheriadis, Theodoros; Mertens, Peter R; Liakopoulos, Vassilios

2018-05-23

Despite optimal management of diabetic kidney disease (DKD) with intensive glycemic control and administration of agents blocking the renin-angiotensin-aldosterone-system, the residual risk for nephropathy progression to end-stage-renal-disease (ESRD) remains high. Sodium-glucose co-transporter type 2 (SGLT-2)-inhibitors represent a newly-introduced anti-diabetic drug class with pleiotropic actions extending above their glucose-lowering efficacy. Herein, we provide an overview of preclinical and clinical-trial evidence supporting a protective effect of SGLT-2 inhibitors on DKD. A systematic literature search of bibliographic databases to identify preclinical studies and randomized trials evaluating the effects SGLT-2 inhibitors on DKD. Preclinical studies performed in animal models of DKD support the renoprotective action of SGLT-2 inhibitors showing that these agents exert albuminuria-lowering effects and reverse glomerulosclerosis. The renoprotective action of SGLT-2 inhibitors is strongly supported by human studies showing that these agents prevent the progression of albuminuria and retard nephropathy progression to ESRD. This beneficial effect of SGLT-2 inhibitors is not fully explained by their glucose-lowering properties. Attenuation of glomerular hyperfiltration and improvement in a number of surrogate risk factors, including associated reduction in systemic blood pressure, body weight, and serum uric acid levels may represent plausible mechanistic explanations for the cardio-renal protection offered by SGLT-2 inhibitors. Furthermore, the tubular cell metabolism seems to be altered towards a ketone-prone pathway with protective activities. SGLT-2 inhibition emerges as a novel therapeutic approach of type 2 diabetes with anticipated benefits towards cardio-renal risk reduction. Additional research efforts are clearly warranted to elucidate this favorable effect in patients with overt DKD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Piperine, a Natural Bioenhancer, Nullifies the Antidiabetic and Antioxidant Activities of Curcumin in Streptozotocin-Diabetic Rats

PubMed Central

Arcaro, Carlos Alberto; Gutierres, Vânia Ortega; Assis, Renata Pires; Moreira, Thais Fernanda; Costa, Paulo Inácio; Baviera, Amanda Martins; Brunetti, Iguatemy Lourenço

2014-01-01

Knowing that curcumin has low bioavailability when administered orally, and that piperine has bioenhancer activity by inhibition of hepatic and intestinal biotransformation processes, the aim of this study was to investigate the antidiabetic and antioxidant activities of curcumin (90 mg/kg) and piperine (20 or 40 mg/kg), alone or co-administered, incorporated in yoghurt, in streptozotocin (STZ)-diabetic rats. The treatment for 45 days of STZ-diabetic rats with curcumin-enriched yoghurt improved all parameters altered in this experimental model of diabetes: the body weight was increased in association with the weight of skeletal muscles and white adipose tissues; the progressive increase in the glycemia levels was avoided, as well as in the glycosuria, urinary urea, dyslipidemia, and markers of liver (alanine and aspartate aminotransferases and alkaline phosphatase) and kidney (urinary protein) dysfunction; the hepatic oxidative stress was decreased, since the activities of the antioxidant enzymes superoxide dismutase, catalase and gluthatione peroxidase were increased, and the levels of malondialdehyde and protein carbonyl groups were reduced. The dose of 20 mg/kg piperine also showed antidiabetic and antioxidant activities. The treatment of STZ-diabetic rats with both curcumin and 20 mg/kg piperine in yoghurt did not change the antidiabetic and antioxidant activities of curcumin; notably, the treatment with both curcumin and 40 mg/kg piperine abrogated the beneficial effects of curcumin. In addition, the alanine aminotransferase levels were further increased in diabetic rats treated with curcumin and 40 mg/kg piperine in comparison with untreated diabetic rats. These findings support that the co-administration of curcumin with a bioenhancer did not bring any advantage to the curcumin effects, at least about the antidiabetic and antioxidant activities, which could be related to changes on its biotransformation. PMID:25469699

An overview on antidiabetic medicinal plants having insulin mimetic property

PubMed Central

Patel, DK; Prasad, SK; Kumar, R; Hemalatha, S

2012-01-01

Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8% of the world's population and is anticipated to cross 5.4% by the year 2025. Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycaemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulinomimetic or insulin secretagogues activity) and active phytoconstituents having insulin mimetics activity. From the review it was suggested that, plant showing hypoglycemic potential mainly belongs to the family Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae and Araliaceae. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. The review describes some new bioactive drugs and isolated compounds from plants such as roseoside, epigallocatechin gallate, beta-pyrazol-1-ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3- O-alpha-L rhamnoside, glycyrrhetinic acid, dehydrotrametenolic acid, strictinin, isostrictinin, pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents. Thus, from the review majorly, the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols, flavonoids, terpenoids, coumarins and other constituents which show reduction in blood glucose levels. The review also discusses the management aspect of diabetes mellitus using these plants and their active principles. PMID:23569923

Effects of culture medium compositions on antidiabetic activity and anticancer activity of marine endophitic bacteria isolated from sponge

NASA Astrophysics Data System (ADS)

Maryani, Faiza; Mulyani, Hani; Artanti, Nina; Udin, Linar Zalinar; Dewi, Rizna Triana; Hanafi, Muhammad; Murniasih, Tutik

2017-01-01

High diversity of Indonesia marine spesies and their ability in producing secondary metabolite that can be used as a drug candidate cause this fascinating topic need to explore. Most of marine organisms explored to discover drug is macroorganism whereas microorganism (such as Indonesia marine bacteria) is very limited. Therefore, in this report, antidiabetic and anticancer activity of Indonesia marine bacteria isolated from Sponges's extract have been studied. Bacteria strain 8.9 which are collection of Research Center for Oseanography, Indonesian Institute of Sciences were from Barrang Lompo Island, Makasar, Indonesia. Bacteria were cultured in different culture medium compositions (such as: different pH, source of glucose and water) for 48 hours on a shaker, then they were extracted with ethyl asetate. Extracts of bacteria were tested by DPPH method (antioxidant activity), alpha glucosidase inhibitory activity method (antidiabetic activity), and Alamar Blue assay (anticancer activity) at 200 ppm. According to result, extract of bacteria in pH 8.0 exhibited the greatest antioxidant (19.27% inhibition), antidiabetic (63.95% inhibition) and anticancer activity of T47D cell line (44.62% cell viability) compared to other extracts. However, effect of addition of sugar sources (such as: glucose, sucrose, and soluble starch) and effect of addition of water/sea water exhibited less influence on their bioactivities. In conclusion, Indonesia marine bacteria isolated from sponge have potential a source of bioactive compound in drug discovery field.

Antihyperglycemic effect of crude extracts of some Egyptian plants and algae.

PubMed

AbouZid, Sameh Fekry; Ahmed, Osama Mohamed; Ahmed, Rasha Rashad; Mahmoud, Ayman; Abdella, Ehab; Ashour, Mohamed Badr

2014-03-01

Diabetes mellitus is a major global health problem. Various plant extracts have proven antidiabetic activity and are considered as promising substitution for antidiabetic drugs. The antihyperglycemic effect of 16 plants and 4 algae, commonly used in Egypt for the treatment of diabetes mellitus, was investigated. A diabetes model was induced by intraperitoneal injection of nicotinamide (120 mg/kg body weight [b.wt.]), then streptozotocin (200 mg/kg b.wt.) after 15 min. Hydroethanolic extracts (80%) of the plants and algae under investigation were prepared. The extracts were orally administered to nicotinamide-streptozotocin-induced diabetic mice by a gastric tube at doses 10 or 50 mg/kg b.wt. for 1 week. The antidiabetic activity was assessed by detection of serum glucose concentrations at the fasting state and after 2 h of oral glucose loading (4.2 mg/kg b.wt.). Extracts prepared from Cassia acutifolia, Fraxinus ornus, Salix aegyptiaca, Cichorium intybus, and Eucalyptus globulus showed the highest antihyperglycemic activity among the tested plants. Extracts prepared from Sonchus oleraceus, Bougainvillea spectabilis (leaves), Plantago psyllium (seeds), Morus nigra (leaves), and Serena repens (fruits) were found to have antihyperglycemic potentials. Extracts prepared from Caulerpa lentillifera and Spirulina versicolor showed the most potent antihyperglycemic activity among the tested algae. However, some of the tested plants have insulinotropic effects, all assessed algae have not. Identification of lead compounds from these plants and algae for novel antidiabetic drug development is recommended.

GPR40 partial agonists and AgoPAMs: Differentiating effects on glucose and hormonal secretions in the rodent

PubMed Central

Pachanski, Michele J.; Kirkland, Melissa E.; Kosinski, Daniel T.; Mane, Joel; Cheewatrakoolpong, Boonlert; Xue, Jiyan; Szeto, Daphne; Forrest, Gail; Miller, Corin; Bunzel, Michelle; Plummer, Christopher W.; Chobanian, Harry R.; Miller, Michael W.; Souza, Sarah; Thomas-Fowlkes, Brande S.; Ogawa, Aimie M.; Weinglass, Adam B.; Di Salvo, Jerry; Li, Xiaoyan; Feng, Yue; Tatosian, Daniel A.; Howard, Andrew D.; Colletti, Steven L.

2017-01-01

GPR40 agonists are effective antidiabetic agents believed to lower glucose through direct effects on the beta cell to increase glucose stimulated insulin secretion. However, not all GPR40 agonists are the same. Partial agonists lower glucose through direct effects on the pancreas, whereas GPR40 AgoPAMs may incorporate additional therapeutic effects through increases in insulinotrophic incretins secreted by the gut. Here we describe how GPR40 AgoPAMs stimulate both insulin and incretin secretion in vivo over time in diabetic GK rats. We also describe effects of AgoPAMs in vivo to lower glucose and body weight beyond what is seen with partial GPR40 agonists in both the acute and chronic setting. Further comparisons of the glucose lowering profile of AgoPAMs suggest these compounds may possess greater glucose control even in the presence of elevated glucagon secretion, an unexpected feature observed with both acute and chronic treatment with AgoPAMs. Together these studies highlight the complexity of GPR40 pharmacology and the potential additional benefits AgoPAMs may possess above partial agonists for the diabetic patient. PMID:29053717

Phytochemical screening and study of antioxidant, antimicrobial, antidiabetic, anti-inflammatory and analgesic activities of extracts from stem wood of Pterocarpus marsupium Roxburgh.

PubMed

Pant, Dipak Raj; Pant, Narayan Dutt; Saru, Dil Bahadur; Yadav, Uday Narayan; Khanal, Dharma Prasad

2017-01-01

The main aims of the study were to evaluate the phytochemical constituents and to study the antioxidant, antimicrobial, antidiabetic, anti-inflammatory, and analgesic activities of extracts from stem wood of Pterocarpus marsupium . Ethanol, acetone and isopropyl alcohol (IPA) (1:1) extracts of stem wood of P. marsupium were subjected to phytochemical screening and analysis of biological activities from August 2015 to January 2016. The antioxidant assay was carried out using 2, 2-diphenyl-1-picrylhydrazyl scavenging method, antimicrobial activity testing by cup diffusion method, antidiabetic test evaluation by oral glucose tolerance test in mice, anti-inflammatory effect was evaluated by hind paw edema method in mice and analgesic test evaluation by a chemical writhing method in mice. The results of the study revealed that P. marsupium is a source of various phytoconstituents such as alkaloids, glycosides, saponins, tannins, proteins, carbohydrates, cardiac glycosides, flavonoids, and terpenoids. Both the acetone and IPA extract as well as the ethanol extract of stem wood of P. marsupium exhibited a dose-dependent antioxidant activity. Acetone and IPA extract showed antibacterial activity against Gram-positive bacteria, while the ethanolic extract was found to possess antidiabetic activity. The antidiabetic activity of the extract was found to be time and dose-dependent. Similarly, the acetone and IPA extract was found to have anti-inflammatory activity, which was also time and dose-dependent. Furthermore, the ethanolic extract showed analgesic activity, which was dose-dependent. The ethanolic extract was found to be nontoxic. Thus, this study laid sufficient background for the further research on extracts from stem wood of P. marsupium for identification, subsequent purification and isolation of compounds having antibacterial, antidiabetic, anti-inflammatory, and analgesic activities.

An evidence-based practice-oriented review focusing on canagliflozin in the management of type 2 diabetes

PubMed Central

Messana, Joseph A; Schwartz, Stanley S; Townsend, Raymond R

2017-01-01

Caring for patients with type 2 diabetes mellitus (T2DM) has entered an era with many recent additions to the regimens used to clinically control their hyperglycemia. The most recent class of agents approved by the Food and Drug Administration (FDA) for T2DM is the sodium–glucose-linked transporter type 2 (SGLT2) inhibitors, which work principally in the proximal tubule of the kidney to block filtered glucose reabsorption. In the few years attending this new class arrival in the market, there has been a great deal of interest generated by the novel mechanism of action of SGLT2 inhibitors and by recent large outcome trials suggesting benefit on important clinical outcomes such as death, cardiovascular disease and kidney disease progression. In this review, we focus on canagliflozin, the first-in-class marketed SGLT2 inhibitor in the USA. In some cases, we included data from other SGLT2 inhibitors, such as outcomes in clinical trials, important insights on clinical features and benefits, and adverse effects. These agents represent a fundamentally different way of controlling blood glucose and for the first time in T2DM care to offer the opportunity to reduce glucose, blood pressure, and weight with effects sustained for at least 2 years. Important side effects include genital mycotic infections and the potential for orthostatic hypotension and rare instances of normoglycemic ketoacidosis. Active ongoing clinical trials promise to deepen our experience with the potential benefits, as well as the clinical risks attending the use of this new group of antidiabetic agents. PMID:28255241

[Obesity: a review of currently used antiobesity drugs and new compounds in clinical development].

PubMed

Zieba, Remigiusz

2007-10-19

This review summarizes data on currently used antiobesity drugs and new compounds under clinical development. Three antiobesity drugs are currently accepted for long-term use. Sibutramine is a noradrenaline and serotonin reuptake inhibitor which reduces body weight by about 4-5 kg but increases heart rate and arterial blood pressure. Orlistat is a gastrointestinal lipase inhibitor which results in mean weight loss by about 3 kg and reduces the incidence of type 2 diabetes in patients with impaired glucose tolerance; however, adverse gastrointestinal effects have been observed. Rimonabant is an endocannabinoid CB1 receptor antagonist which induces a 4-5 kg mean weight loss and improves glycemic and lipid profiles, but it induces anxiety and depressive disorders. Unfortunately, there are no data on the chronic administration of these drugs. Other drugs can induce weight loss, e.g. some antidepressants, antiseizure agents, and antidiabetic drugs. The moderate efficacy of currently used antiobesity drugs has led to an intense effort to identify new, safe antiobesity drugs with better therapeutic profiles. The new antiobesity drugs under clinical development include: 1) agents that affect neurotransmitters in the central nervous system, including noradrenaline and dopamine reuptake inhibitors (bupropion, radafaxine), selective 5HT2C receptor agonists (lorcaserin), and selective 5HT6 receptor antagonists, 2) agents that modulate the activity of neuropeptides influencing food intake, including leptin analogues, human ciliary neurotrophic factor (Axokine), neuropeptide Y antagonists, and melanine-concentrating hormone antagonists, 3) agents that affect the peripheral satiety signals and brain-gut axis, e.g. selective cholecystokinin receptor A agonists, PYY3-36, agents decreasing ghrelin activity, 4) thermogenic agents, e.g. selective beta3 receptor agonists and selective thyroid hormone receptor beta agonists, and 5) others, e.g. human growth hormone fragment (AOD9604) and gastrointestinal lipase inhibitor (cetilistat).

Antidiabetic plant-derived nutraceuticals: a critical review.

PubMed

Naveen, Jayapal; Baskaran, Vallikannan

2018-06-01

Diabetes mellitus (DM) is one of the major health problems in the world, especially amongst the urban population. Chemically synthesized drugs used to decrease the ill effects of DM and its secondary complications cause adverse side effects, viz., weight gain, gastrointestinal disturbances, and heart failure. Currently, various other approaches, viz., diet control, physical exercise and use of antidiabetic plant-derived molecules/foods are advocated to manage DM, as they are economical with fewer or no side effects. This review mainly focuses on antidiabetic plants, chemically characterized plant molecules and plant-based foods in the treatment of DM. Very little science-based evidence is available on the mechanism of action of plant-derived food molecules on the DM targets. Critical DM targets include α-amylase, α-glucosidase, DPP-IV, aldose reductase, PPAR-γ, AMP kinase and GLUT4. In-depth studies carried out on a few of those targets with specific mechanisms of action are addressed in this review. This review may help future researchers in identifying a right plant molecule to treat DM or to develop food formulations for DM management.

Polyphenols and Glycemic Control

PubMed Central

Kim, Yoona; Keogh, Jennifer B.; Clifton, Peter M.

2016-01-01

Growing evidence from animal studies supports the anti-diabetic properties of some dietary polyphenols, suggesting that dietary polyphenols could be one dietary therapy for the prevention and management of Type 2 diabetes. This review aims to address the potential mechanisms of action of dietary polyphenols in the regulation of glucose homeostasis and insulin sensitivity based on in vitro and in vivo studies, and to provide a comprehensive overview of the anti-diabetic effects of commonly consumed dietary polyphenols including polyphenol-rich mixed diets, tea and coffee, chocolate and cocoa, cinnamon, grape, pomegranate, red wine, berries and olive oil, with a focus on human clinical trials. Dietary polyphenols may inhibit α-amylase and α-glucosidase, inhibit glucose absorption in the intestine by sodium-dependent glucose transporter 1 (SGLT1), stimulate insulin secretion and reduce hepatic glucose output. Polyphenols may also enhance insulin-dependent glucose uptake, activate 5′ adenosine monophosphate-activated protein kinase (AMPK), modify the microbiome and have anti-inflammatory effects. However, human epidemiological and intervention studies have shown inconsistent results. Further intervention studies are essential to clarify the conflicting findings and confirm or refute the anti-diabetic effects of dietary polyphenols. PMID:26742071

Anti-diabetic effect of pyroglutamic acid in type 2 diabetic Goto-Kakizaki rats and KK-Ay mice.

PubMed

Yoshinari, Orie; Igarashi, Kiharu

2011-10-01

With the rapidly increasing prevalence of type 2 diabetes mellitus (T2DM), specific dietary components with anti-diabetic efficacy could be one strategy with therapeutic potential. In the present study, the anti-diabetic effects of an amino acid, pyroglutamic acid (PA), found in vegetables and fruits were investigated in T2DM models using Goto-Kakizaki (GK) rats and KK-Ay mice by measuring glucose tolerance and other markers of diabetes. Moreover, the effect of PA on gene expression in GK rats was measured by DNA microarray analysis. Oral glucose tolerance and serum insulin levels were reduced by PA in both animal models. Serum and liver total cholesterol levels were also improved by PA. Expression of genes involved with gluconeogenesis and those involved with its related transcription factor were down-regulated by feeding PA. In KK-Ay mice, the glucokinase:glucose-6-phosphatase (G6Pase) activity ratio increased. From these results, it is suggested that dietary PA beneficially modifies glucose and lipid metabolism in diabetic animals, and can potentially contribute to the mitigation of T2DM.

Macrophage PPARγ is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones

PubMed Central

Hevener, Andrea L.; Olefsky, Jerrold M.; Reichart, Donna; Nguyen, M.T. Audrey; Bandyopadyhay, Gautam; Leung, Ho-Yin; Watt, Matthew J.; Benner, Chris; Febbraio, Mark A.; Nguyen, Anh-Khoi; Folian, Brian; Subramaniam, Shankar; Gonzalez, Frank J.; Glass, Christopher K.; Ricote, Mercedes

2007-01-01

PPARγ is required for fat cell development and is the molecular target of antidiabetic thiazolidinediones (TZDs), which exert insulin-sensitizing effects in adipose tissue, skeletal muscle, and liver. Unexpectedly, we found that inactivation of PPARγ in macrophages results in the development of significant glucose intolerance plus skeletal muscle and hepatic insulin resistance in lean mice fed a normal diet. This phenotype was associated with increased expression of inflammatory markers and impaired insulin signaling in adipose tissue, muscle, and liver. PPARγ-deficient macrophages secreted elevated levels of factors that impair insulin responsiveness in muscle cells in a manner that was enhanced by exposure to FFAs. Consistent with this, the relative degree of insulin resistance became more severe in mice lacking macrophage PPARγ following high-fat feeding, and these mice were only partially responsive to TZD treatment. These findings reveal an essential role of PPARγ in macrophages for the maintenance of whole-body insulin action and in mediating the antidiabetic actions of TZDs. PMID:17525798

Antidiabetic Evaluation of Momordica charantia L Fruit Extracts

PubMed Central

Tahira, S; Hussain, F

2014-01-01

To investigate hypoglycaemic, hypolipidaemic and pancreatic beta cell regeneration activities of Momordica charantia L fruits (MC). Alloxan-induced diabetic rabbits were treated with methanolic and ethanolic MC extract. Effects of plant extracts and the drug glibenclamide on serum glucose, lipid profile and pancreatic beta cell were determined after two weeks of treatment. Serum glucose and lipid profiles were assayed by kit methods. Pancreatic tissue histopathology was performed to study pancreatic beta cell regeneration. Momordica charantia extracts produced significant hypoglycaemic effects (p < 0.05). Hypolipidaemic activity of MC was negligible. Momordica charantia supplementations were unable to normalize glucose and lipid profiles. Glibenclamide, a standard drug, not only lowered hyperglycaemia and hyperlipidaemia but also restored the normal levels. Regeneration of pancreatic beta cells by MC extracts was minimal, with fractional improvement produced by glibenclamide. The most significant finding of the present study was a 28% reduction in hyperglycaemia by MC ethanol extracts. To determine reliable antidiabetic potentials of MC, identification of the relevant antidiabetic components and underlying mechanisms is warranted. PMID:25429471

Antidiabetic and hypolipidaemic effects of a methanol/methylene-chloride extract of Laportea ovalifolia (Urticaceae), measured in rats with alloxan-induced diabetes.

PubMed

Momo, C E N; Oben, J E; Tazoo, D; Dongo, E

2006-01-01

A decoction of the leaves of Laportea ovalifolia is widely used in Cameroon for the treatment of several illnesses, including diabetes mellitus. The antidiabetic and hypolipidaemic effects of a methanol/methylene-chloride extract of the aerial parts of L. ovalifolia have now been investigated, in normal rats and rats with diabetes induced by the intraperitoneal injection of alloxan (at 150 mg/kg bodyweight). In the diabetic rats, 2 weeks of daily, intragastric treatment with the L. ovalifolia extract not only produced a significant reduction in the fasting serum glucose concentrations but also lowered the serum concentrations of total cholesterol, triglycerides, and low-density-lipoprotein cholesterol, lowered the ratio of total cholesterol to high-density-lipoprotein (HDL) cholesterol, and increased the serum concentration of HDL cholesterol. At least in rats with alloxan-induced diabetes, the methanol/methylene-chloride extract of L. ovalifolia therefore appears to possess antidiabetic and hypolipidaemic properties.

Antidiabetic potential of some less commonly used plants in traditional medicinal systems of India and Nigeria

PubMed Central

Mohammed, Abubakar; Kumar, Dileep; Rizvi, Syed Ibrahim

2015-01-01

The incidence of diabetes mellitus continue to rise annually all over the world with India and Nigeria having recorded cases of 65.1 and 3.9 million respectively in 2013 and expected to increase by a large amount in 2035. Hyperglycemia is a pre-condition for the development of diabetic complications and is accompanied by an increase in the production of free radicals. The present available treatment option for diabetes like sulfonylurea, metformin and alpha-glucosidase are restricted by their limited actions, secondary failure rates, and side-effects; and unaffordable to the majority of the population. Hence, the need to screen for more medicinal plants with antidiabetic ability due to the fact that plants are; biodegradable, safe and cheap with fewer side-effects. In this review article, we have presented the current status of diabetes in India and Nigeria and the role of some less commonly used medicinal plants from both countries that have antidiabetic potential. PMID:26401390

Farmer to Pharmacist: Curcumin as an Anti-invasive and Antimetastatic Agent for the Treatment of Cancer

NASA Astrophysics Data System (ADS)

Bandyopadhyay, Debasish

2014-12-01

A huge number of compounds are widely distributed in nature and many of these possess medicinal/biological/pharmacological activity. Curcumin, a polyphenol derived from the rhizomes (underground stems) of Curcuma longa Linn (a member of the ginger family, commonly known as turmeric) is a culinary spice and therapeutic used in India for thousands of years to induce color and flavor in food as well as to treat a wide array of diseases. The origin of turmeric as spice and folklore medicine is so old that it is lost in legend. Curcumin has many beneficial pharmacological effects which includes, but are not limited with, antimicrobial, anti-inflammatory, antioxidant, antiviral, antiangiogenic, and antidiabetic activities. Most importantly curcumin possesses immense antitumorigenic effect. It prevents tumor invasion and metastasis in a number of animal models, including models of lung, liver, stomach, colon, breast, esophageal cancer etc. Invasion and metastasis are considered as one of the hallmarks in cancer biology. The pertinent recent applications of curcumin as anti-invasive and antimetastatic agent in in vitro and in vivo and ex vivo studies as well as associated molecular mechanisms have been discussed in this review. Curcumin has also demonstrated the ability to improve patient outcomes in clinical trials.

Farmer to pharmacist: curcumin as an anti-invasive and antimetastatic agent for the treatment of cancer1

PubMed Central

Bandyopadhyay, Debasish

2014-01-01

A huge number of compounds are widely distributed in nature and many of these possess medicinal/biological/pharmacological activity. Curcumin, a polyphenol derived from the rhizomes (underground stems) of Curcuma longa Linn (a member of the ginger family, commonly known as turmeric) is a culinary spice and therapeutic used in India for thousands of years to induce color and flavor in food as well as to treat a wide array of diseases. The origin of turmeric as spice and folklore medicine is so old that it is lost in legend. Curcumin has many beneficial pharmacological effects which includes, but are not limited with, antimicrobial, anti-inflammatory, antioxidant, antiviral, antiangiogenic, neurodegenerative diseases such as Alzheimer disease, and antidiabetic activities. Most importantly curcumin possesses immense antitumorigenic effect. It prevents tumor invasion and metastasis in a number of animal models, including models of lung, liver, stomach, colon, breast, esophageal cancer etc. Invasion and metastasis are considered as one of the hallmarks in cancer biology. The pertinent recent applications of curcumin as anti-invasive and antimetastatic agent in in vitro and in vivo and ex vivo studies as well as associated molecular mechanisms have been discussed in this review. Curcumin has also demonstrated the ability to improve patient outcomes in clinical trials. PMID:25566531

Vildagliptin: a new oral treatment for type 2 diabetes mellitus

PubMed Central

Mathieu, Chantal; Degrande, Evy

2008-01-01

Vildagliptin is a new oral antidiabetic agent that enhances pancreatic islet cell responsiveness to glucose. An extensive clinical program involving approximately 22,000 patients and 7000 patient-years of exposure to vildagliptin has shown that the agent is well tolerated and efficacious in improving glycemic control in patients with type 2 diabetes mellitus (T2DM). Monotherapy trials have shown that significant HbA1c lowering is accompanied by body weight-neutral and lipid-neutral effects, low risk of edema, and low risk of hypoglycemia. These characteristics make vildagliptin a favorable partner for combination therapy. Studies of vildagliptin as an add-on to metformin have shown significant improvements in glycemic control (comparable to that of thiazolidinedione add-on), with the combination being well tolerated and associated with low risks for hypoglycemia and adverse effects on weight or lipid levels. Good tolerability and clinically relevant improvements in glycemic control have also been observed with vildagliptin as an add-on treatment to sulfonylurea, thiazolidinedione, or insulin treatment or in initial combination treatment with pioglitazone. Improved β-cell function and glycemic control have been shown with vildagliptin in subjects with impaired glucose tolerance and in T2DM patients with mild hyperglycemia, with some evidence in the latter suggesting the potential for modifying disease course. PMID:19337548

Hibiscus rosa sinensis Linn. Petals Modulates Glycogen Metabolism and Glucose Homeostasis Signalling Pathway in Streptozotocin-Induced Experimental Diabetes.

PubMed

Pillai, Sneha S; Mini, S

2016-03-01

The prevalence of diabetes mellitus is becoming more and more serious and reaches epidemic proportions worldwide. Scientific research is constantly looking for new agents that could be used as dietary functional ingredients in the fight against diabetes. The objective of the present study was to evaluate the effect of ethyl acetate fraction of Hibiscus rosa sinensis Linn. petals on experimental diabetes at a dose of 25 mg/kg body weight and it was compared with standard anti-diabetic drug metformin. The elevated levels of serum glucose (398.56 ± 35.78) and glycated haemoglobin (12.89 ± 1.89) in diabetic rats were significantly decreased (156.89 ± 14.45 and 6.12 ± 0.49, respectively) by Hibiscus rosa sinensis petals (EHRS) administration. Hepatotoxicity marker enzyme levels in serum were normalized. The fraction supplementation restored the glycogen content by regulating the activities of glycogen metabolizing enzymes. It significantly modulated the expressions of marker genes involved in glucose homeostasis signalling pathway. Histopathological analysis of liver and pancreas supported our findings. The overall effect was comparable with metformin. Hence, our study reveals the role of hibiscus petals for alleviation of diabetes complications, thus it can be propagated as a nutraceutical agent.

Efficacy of Sleeve Gastrectomy with Duodenal-Jejunal Bypass for the Treatment of Obese Severe Diabetes Patients in Japan: a Retrospective Multicenter Study.

PubMed

Naitoh, Takeshi; Kasama, Kazunori; Seki, Yosuke; Ohta, Masayuki; Oshiro, Takashi; Sasaki, Akira; Miyazaki, Yasuhiro; Yamaguchi, Tsuyoshi; Hayashi, Hideki; Imoto, Hirofumi; Tanaka, Naoki; Unno, Michiaki

2018-02-01

The incidence of obesity with type 2 diabetes (T2DM) is increasing in Japan. The main bariatric surgery procedures in Japan are laparoscopic sleeve gastrectomy (LSG) and LSG with duodenal-jejunal bypass (LSG/DJB) because of the high incidence of gastric cancer and difficulty exploring a remnant stomach after gastric bypass. However, few studies have compared the antidiabetic effect of LSG/DJB with LSG alone. The purpose of this study is to compare the antidiabetic effect of LSG/DJB with that of LSG alone in Japanese obese diabetic patients. This was a retrospective multicenter study including 298 cases: 177 and 121 LSG and LSG/DJB cases, respectively. We investigated the antidiabetic effect of these two procedures at 12 months after surgery. Univariate and multivariate analyses were done to evaluate the predictive factors of T2DM remission. The diabetes remission rate at 12 months after surgery was 80.8% for LSG and 86.0% for LSG/DJB. Insulin use and HbA1c ≤ 6.7% were significant predictive factors in multivariate analysis for all patients. In patients with ABCD score ≥ 6, the diabetes remission rate was 94.8% and there was no difference between procedures. Only duration of diabetes and insulin use were significant predictive factors both in univariate and multivariate analyses. However, in cases with ABCD score ≤ 5, the remission rate was 70.3% and procedure type was the most significant predictive factor for diabetes remission (odds ratio [OR] 5.140). Although both LSG and LSG/DJB have good antidiabetic effects in Japanese obese patients, LSG/DJB is more effective for patients with lower ABCD scores.

Improvement of intestinal transport, absorption and anti-diabetic efficacy of berberine by using Gelucire44/14: In vitro, in situ and in vivo studies.

PubMed

Sun, Jianmei; Bao, He; Peng, Yajie; Zhang, Haimin; Sun, Ya; Qi, Jiajun; Zhang, Hailong; Gao, Yang

2018-06-10

This study aims to evaluate the effects of Gelucire44/14 on the in vitro transport, in situ intestinal absorption, as well as in vivo antidiabetic efficacy of berberine (BBR). In the in vitro study, Gelucire44/14 (0.1%, v/v) increased the absorptive transport of BBR across the intestinal membrane of a rat and reduced the relative transport in the secretory direction, thus demonstrating its potential inhibitory effect on intestinal P-glycoprotein (P-gp). In the in situ absorption study, Gelucire44/14 (0.1%, v/v) increased BBR absorption, and this enhancing effect was more significant in the ileum than in the colon of a rat. Oral delivery of BBR with Gelucire44/14 (0.1%, v/v) to diabetic mice, compared with the BBR group, induced a significant hypoglycemic effect on day 7 and day 12 after administration. This result was well correlated with the results of the in vitro study, indicating the important contribution of the P-gp inhibitory effect of Gelucire44/14 to the improvement of the antidiabetic efficacy in vivo. In addition, Gelucire44/14 (0.1%, v/v) neither increased the levels of protein and lactate dehydrogenase in intestinal perfusion nor changed the morphology of the rat intestinal epithelium relative to those of the negative control. This finding suggested that 0.1% (v/v) Gelucire44/14 caused no apparent membrane damage to rat intestine. In conclusion, Gelucire44/14 exhibited potential for enhancing the oral absorption of BBR, thereby improving the antidiabetic efficacy of BBR. Copyright © 2018 Elsevier B.V. All rights reserved.

Effectiveness and clinical inertia in patients with antidiabetic therapy.

PubMed

Machado-Duque, Manuel Enrique; Ramírez-Riveros, Adriana Carolina; Machado-Alba, Jorge Enrique

2017-06-01

To establish the effectiveness of antidiabetic therapy and the frequency of clinical inertia in the management of type 2 diabetes mellitus in Colombia. A cross-sectional study with follow-up of patients who had been treated for at least 1 year and were receiving medical consultation for antidiabetic treatment. Effectiveness was established when haemoglobin-A1c levels were <7% and when clinical inertia was reached, which was defined as no therapeutic modifications despite not achieving management controls. Sociodemographic, clinical and pharmacological variables were evaluated, and multivariate analyses were performed. In total, 363 patients with type 2 diabetes mellitus were evaluated, with a mean age of 62.0±12.2 years. A total of 1,016 consultations were evaluated, and the therapy was effective at the end of the follow-up in 57.9% of cases. Clinical inertia was found in 56.8% of patients who did not have metabolic control. The most frequently prescribed medications were metformin (84.0%), glibenclamide (23.4%) and insulin glargine (20.7%). Moreover, 57.6% of the patients were treated with two or more antidiabetic medications. Having metabolic control in the first consult of the follow-up was a protective factor against clinical inertia in the subsequent consultations (OR: 0.08; 95%CI: 0.04-0.15; P<.001). The effectiveness of treatment for patients with type 2 diabetes mellitus has increased in Colombia, and for the first time, clinical inertia was identifiable and quantifiable and found in similar proportions to other countries. Clinical inertia is a relevant condition given that it interferes with the possibility of controlling this pathology. © 2017 John Wiley & Sons Ltd.

Efficacy and safety profile evaluation of acarbose alone and in association with other antidiabetic drugs: a systematic review.

PubMed

Derosa, Giuseppe; Maffioli, Pamela

2012-06-01

Epidemiologic studies have revealed that postprandial hyperglycemia significantly contributes to high glycated hemoglobin concentrations and could be linked to the development of chronic diabetic complications. The purpose of our review was to evaluate the clinical efficacy and safety profile of treatment with acarbose alone and combined with other antidiabetic drugs. A systematic search strategy was developed to identify randomized controlled trials included in MEDLINE and the Cochrane Register of Controlled Trials. The terms acarbose, α-glucosidase inhibitors, type 2 diabetes, adverse events, combination therapy, and postprandial glucose were incorporated into an electronic search strategy that included the Dickersin filter for randomized controlled trials. To qualify for inclusion, clinical trials had to be randomized trials comparing treatment with acarbose at any dosage with any other antidiabetic drug in patients with type 2 diabetes mellitus or impaired glucose tolerance. Eligible trials had to present results on glycemic control or adverse events. Trial participants needed to be affected by type 2 diabetes mellitus or have impaired glucose tolerance, and the intervention had to include acarbose at any dosage as monotherapy or combined with other antidiabetic drugs. A validated 3-item scale was used to evaluate the overall reporting quality of the trials selected for inclusion in the present review. Nineteen trials were included. Treatment with acarbose significantly reduced glycated hemoglobin levels when given as monotherapy and as an add-on to other antidiabetic drug treatment (P < 0.0001). Acarbose treatment was effective in patients with uncontrolled type 2 diabetes and in patients with apparently good metabolic control owing to its positive effect on postprandial hyperglycemia (P < 0.0001). Treatment with acarbose seemed to improve the lipid profile (P < 0.05), reduce circulating levels of cell adhesion molecules (P < 0.05), reduce intima-media thickness progression (P = 0.01), and reverse impaired glucose tolerance to normal glucose tolerance (P < 0.0001). When current therapy is not adequate to obtain glycemic control, acarbose could be an option as monotherapy and as an add-on to other antidiabetic drug treatment, especially when postprandial hyperglycemia is the main concern. Long-term studies are needed to determine whether the effects observed with acarbose use are maintained over the years. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Curcumin as potential therapeutic natural product: a nanobiotechnological perspective.

PubMed

Shome, Soumitra; Talukdar, Anupam Das; Choudhury, Manabendra Dutta; Bhattacharya, Mrinal Kanti; Upadhyaya, Hrishikesh

2016-12-01

Nanotechnology-based drug delivery systems can resolve the poor bioavailability issue allied with curcumin. The therapeutic potential of curcumin can be enhanced by making nanocomposite preparation of curcumin with metal oxide nanoparticles, poly lactic-co-glycolic acid (PLGA) nanoparticles and solid lipid nanoparticles that increases its bioavailability in the tissue. Curcumin has manifold therapeutic effects which include antidiabetic, antihypertensive, anticancer, anti-inflammatory and antimicrobial properties. Curcumin can inhibit diabetes, heavy metal and stress-induced hypertension with its antioxidant, chelating and inhibitory effects on the pathways that lead to hypertension. Curcumin is an anticancer agent that can prevent abnormal cell proliferation. Nanocurcumin is an improved form of curcumin with enhanced therapeutic properties due to improved delivery to the diseased tissue, better internalization and reduced systemic elimination. Curcumin has multiple pharmacologic effects, but its poor bioavailability reduces its therapeutic effects. By conjugating curcumin to metal oxide nanoparticles or encapsulation in lipid nanoparticles, dendrimers, nanogels and polymeric nanoparticles, the water solubility and bioavailability of curcumin can be improved and thus increase its pharmacological effectiveness. © 2016 Royal Pharmaceutical Society.

In Vitro Screening of Three Indian Medicinal Plants for Their Phytochemicals, Anticholinesterase, Antiglucosidase, Antioxidant, and Neuroprotective Effects

PubMed Central

Penumala, Mohan; Zinka, Raveendra Babu; Shaik, Jeelan Basha

2017-01-01

Cooccurrence of Diabetes Mellitus and Alzheimer's disease in elder people prompts scientists to develop multitarget agents that combat causes and symptoms of both diseases simultaneously. In line with this modern paradigm and as a follow-up to our previous studies, the present study is designed to investigate the crude methanolic extracts and subsequent CHCl3, n-BuOH, and H2O fractions of Acalypha alnifolia, Pavetta indica, and Ochna obtusata for their inhibitory activities towards specific targets involved in AD and DM, namely, acetylcholinesterase, butyrylcholinesterase, and α-glucosidase (α-Glc). The methanolic extract and its derived chloroform fractions exhibited remarkable inhibitory capacities with IC50 values being found at the μg/mL level. Further studies on most active chloroform fractions presented a prominent ability to scavenge DPPH and ABTS reactive species and highest neuroprotective effect against H2O2 induced cell injury. Phytochemical analysis showed a large amount of phenolics, flavonoids, and terpenoids in active fractions. In conclusion, A. alnifolia, P. indica, and O. obtusata could be promising sources for the treatment of AD and DM since these fractions induced significant anticholinesterase, antidiabetic, antioxidant, and neuroprotection effects attributable to phenolic, flavonoid, and terpenoid contents and encourage further studies for development of multifunctional therapeutic agent for AD and DM dual therapy. PMID:29204442

Phytochemical Screening, Alpha-Glucosidase Inhibition, Antibacterial and Antioxidant Potential of Ajuga bracteosa Extracts.

PubMed

Hafeez, Kokab; Andleeb, Saiqa; Ghousa, Tahseen; Mustafa, Rozina G; Naseer, Anum; Shafique, Irsa; Akhter, Kalsoom

2017-01-01

Ajuga bracteosa, a medicinal herb, is used by local community to cure a number of diseases such as inflammation, jaundice bronchial asthma, cancer and diabetes. The aim of present work was to evaluate the antioxidant potential, in vitro antidiabetic and antimicrobial effects of A. bracteosa. n-hexane, ethyl acetate, chloroform, acetone, methanol and aqueous extracts of Ajuga bracteosa roots, were prepared via maceration. Antibacterial activity was carried out by agar well diffusion method. Quantitative and qualitative phytochemical screening was done. The antioxidant activity was determined by iron (II) chelating activity, iron reducing power, DPPH, and ABTS free radical scavenging methods, Antidiabetic activity was evaluated through inhibition of α-glucosidase assay. Phytochemical analysis showed the presence of phenols, flavonoids, tannins, saponins, quinines, terpenoids, xanthoproteins, glycosides, carbohydrates, steroids, phytosterols and amino acids. DPPH and ABTS potential values were recorded as 61.92% to 88.84% and 0.11% to 38.82%, respectively. Total phenolic and total flavonoid contents were expressed as gallic acid and rutin equivalents. Total iron content was expressed as FeSO4 equivalents. Chloroform and n-hexane extracts showed significant enzyme inhibition potential with IC50 values of 29.92 μg/ml and 131.7 μg/ml respectively. Aqueous extract showed maximum inhibition of E. coli, S. typhimurium, E. amnigenus, S. pyogenes, and S. aureus, (18.0±1.0 mm, 12.5±0.7 mm, 17.0±0.0 mm, 11.0±0.0 mm and 15.3±2.0 mm mm), respectively. Similarly, n-hexane extract showed maximum inhibition of E. coli, E. amnigenus, S. aureus (11.6±1.5 mm; 11.3±1.5 mm; 13.3±0.5 mm). This study also shows that n-hexane, chloroform, ethyl acetate and aqueous extracts of A. bracteosa root possess α-glucosidase inhibitory activities and therefore it may be used as hypoglycemic agents in the management of postprandial hyperglycemia. Ajuga bracteosa root extracts may provide a basis for development of antioxidant, antimicrobial and antidiabetic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Metformin: an old but still the best treatment for type 2 diabetes

PubMed Central

2013-01-01

The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals. In this setting, metformin, an old and widely accepted first line agent, stands out not only for its antihyperglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution. These properties may have contributed to the decrease of adverse cardiovascular outcomes otherwise not attributable to metformin’s mere antihyperglycemic effects. Several other classes of oral antidiabetic agents have been recently launched, introducing the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs. There is increasing evidence from in vivo and in vitro studies supporting its anti-proliferative role in cancer and possibly a neuroprotective effect. Metformin’s negligible risk of hypoglycemia in monotherapy and few drug interactions of clinical relevance give this drug a high safety profile. The tolerability of metformin may be improved by using an appropiate dose titration, starting with low doses, so that side-effects can be minimized or by switching to an extended release form. We reviewed the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits beyond its glycemic effect. We also discuss its potential role for a variety of insulin resistant and pre-diabetic states, obesity, metabolic abnormalities associated with HIV disease, gestational diabetes, cancer, and neuroprotection. PMID:23415113

A stewardship intervention program for safe medication management and use of antidiabetic drugs.

PubMed

Zhao, Rui-yi; He, Xiao-wen; Shan, Yan-min; Zhu, Ling-ling; Zhou, Quan

2015-01-01

Diabetes patients are complex due to considerations of polypharmacy, multimorbidities, medication adherence, dietary habits, health literacy, socioeconomic status, and cultural factors. Meanwhile, insulin and oral hypoglycemic agents are high-alert medications. Therefore it is necessary to require a multidisciplinary team's integrated endeavors to enhance safe medication management and use of antidiabetic drugs. A 5-year stewardship intervention program, including organizational measures and quality improvement activities in storage, prescription, dispensing, administration, and monitoring, was performed in the Second Affiliated Hospital of Zhejiang University, People's Republic of China, a 3,200-bed hospital with 3.5 million outpatient visits annually. The Second Affiliated Hospital of Zhejiang University has obtained a 100% implementation rate of standard storage of antidiabetic drugs in the Pharmacy and wards since August 2012. A zero occurrence of dispensing errors related to highly "look-alike" and "sound-alike" NovoMix 30(®) (biphasic insulin aspart) and NovoRapid(®) (insulin aspart) has been achieved since October 2011. Insulin injection accuracy among ward nurses significantly increased from 82% (first quarter 2011) to 96% (fourth quarter 2011) (P<0.05). The number of medication administration errors related to insulin continuously decreased from 20 (2011) to six (2014). The occurrence rate of hypoglycemia in non-endocrinology ward diabetes inpatients during 2011-2013 was significantly less than that in 2010 (5.03%-5.53% versus 8.27%) (P<0.01). Percentage of correct management of hypoglycemia by nurses increased from 41.5% (April 2014) to 67.2% (August 2014) (P<0.01). The percentage of outpatient diabetes patients receiving standard insulin injection education increased from 80% (April 2012) to 95.2% (October 2012) (P<0.05). Insulin injection techniques among diabetes outpatients who started to receive insulin were better than indicated in data from two questionnaire surveys in the literature, including the percentage checking injection sites prior to injection (85.6%), priming before injection (98.1%), rotation of injecting sites (98.1%), remixing before use (94.5%), keeping the pen needle under the skin for >10 seconds (99.4%), and using the pen needle only once (88.7%). On-site inspection indicated of great improvement in the percentage of drug-related problems in the antidiabetes regimen between the first and second quarter of 2014 (1.08% versus 0.28%) (P<0.05). Quality improvements in safe medication management and use of antidiabetic drugs can be achieved by multidisciplinary collaboration among pharmacists, nurses, physicians, and information engineers.

Open randomised prospective comparative multi-centre intervention study of patients with cystic fibrosis and early diagnosed diabetes mellitus

PubMed Central

2014-01-01

Background Diabetes mellitus may be present in patients with cystic fibrosis starting in the second decade of life. The prevalence increases rapidly with increasing age. As life-expectancy increases in cystic fibrosis, cystic fibrosis related diabetes will be diagnosed more frequently in the future. Up to date, no data are available to answer the question if cystic fibrosis related diabetes should always initially be treated by insulin therapy. Missing data regarding oral antidiabetic treatment of newly diagnosed cystic fibrosis related diabetes are an important reason to recommend insulin treatment. Several centres report the successful management of cystic fibrosis related diabetes using oral anti-diabetic drugs at least for some years. Oral therapies would be less invasive for a patient group which is highly traumatized by a very demanding therapy. Based on an initiative of the German Mukoviszidosis-Foundation, the present study tries to answer the question, whether oral therapy with repaglinide is as effective as insulin therapy in cystic fibrosis patients with early diagnosed diabetes mellitus. Methods/Design In all cystic fibrosis patients with an age of 10 years or older, an oral glucose tolerance test is recommended. The result of this test is classified according to the WHO cut off values. It is required to have two diabetes positive oral glucose tolerance tests for the diagnosis of diabetes mellitus. This study is a multi-national, multicentre, open labelled, randomized and prospective controlled parallel group’s trial, with 24 months treatment. The primary objective of this trial is to compare the glycaemic control of oral therapy with Repaglinide with insulin injections in patients with cystic fibrosis related diabetes after 2 years of treatment. The trial should include 74 subjects showing cystic fibrosis related diabetes newly diagnosed by oral glucose tolerance test during annual screening for cystic fibrosis related diabetes. Patients are randomised by central fax randomisation. Primary endpoint is mean HbA1c after 24 months of treatment. Secondary endpoints are change in FEV1% predicted and change in BMI-Z-score. Discussion There is only one prospective study comparing oral antidiabetic drugs to insulin in the treatment of CFRD without fasting hyperglycaemia. The results regarding BMI after 6 months and 12 months showed an improvement for the insulin treated patients and were inconsistent for those treated with repaglinide. HbA1c and lung function (FEV1%pred) were unchanged for either group. The authors compared the changes -12 months to baseline and baseline to +12 months separately for each group. Therefore a direct comparison of the effect of repaglinide versus insulin on BMI, HbA1c and FEV1%pred was not presented. According to our protocol, we will directly compare treatment effects (HbA1c, BMI, FEV1%pred) in between both groups. The actual Cochrane report regarding “Insulin and oral agents for managing CFRD” stated that further studies are needed to establish whether there is clear benefit for hypoglycemic agents. We expect that the results of our study will help to address this clinical need. Trial registration ClinicalTrials.gov Identifier: NCT00662714 PMID:24620855

Characteristics and in vitro Anti-diabetic Properties of the Korean Rice Wine, Makgeolli Fermented with Laminaria japonica

PubMed Central

Choi, Jae-Suk; Seo, Hyo Ju; Lee, Yu-Ri; Kwon, Su-Jung; Moon, Sun Hwa; Park, Sun-Mee; Sohn, Jae Hak

2014-01-01

New in vitro anti-diabetes makgeolli was produced from rice by adding various quantities of Laminaria japonica, and the fermentation characteristics of the L. japonica makgeolli during the fermentation process were investigated. The contents of alcohol and reducing sugar, and viable count of yeast, of L. japonica makgeolli were not significantly changed when the proportion of L. japonica was increased. The total acid content decreased with an increase in L. japonica concentration; the pH and total bacterial cell count increased in proportion with the increase in L. japonica concentration. The L. japonica makgeolli contents of free sugars, such as fructose, glucose, and sucrose, and of organic acids, such as acetic acid, citric acid, succinic acid, and lactic acid, were altered during fermentation and showed various patterns. The effects of the quantity of L. japonica added on the acceptability and anti-diabetes activities of L. japonica makgeolli were also investigated. In a sensory evaluation, L. japonica makgeolli brewed by adding 2.5 or 5% L. japonica to the mash showed the best overall acceptability; the 12.5% L. japonica sample was least favored due to its seaweed flavor. L. japonica addition did not increase the peroxynitrite-scavenging activity of makgeolli. L. japonica makgeolli showed potent anti-diabetes activity, particularly that containing >7.5% L. japonica. Therefore, L. japonica makgeolli may represent a new functional makgeolli with anti-diabetes properties. PMID:25054108

Novel drug delivery system: an immense hope for diabetics.

PubMed

Rai, Vineet Kumar; Mishra, Nidhi; Agrawal, Ashish Kumar; Jain, Sanyog; Yadav, Narayan Prasad

2016-09-01

Existing medication systems for the treatment of diabetes mellitus (DM) are inconvenient and troublesome for effective and safe delivery of drugs to the specific site. Therefore, investigations are desired to deliver antidiabetics using novel delivery approaches followed by their commercialization. The present review aims to provide a compilation on the latest development in the field of novel drug delivery systems (NDDSs) for antidiabetics with special emphasis on particulate, vesicular and miscellaneous systems. Review of literature (restricted to English language only) was done using electronic databases like Pubmed® and Scirus, i.e. published during 2005-2013. The CIMS/MIMS India Medical Drug Information eBook was used regarding available marketed formulation of antidiabetic drugs. Keywords used were "nanoparticle", "microparticle", "liposomes", "niosomes", "transdermal systems", "insulin", "antidiabetic drugs" and "novel drug delivery systems". Single inclusion was made for one article. If in vivo study was not done then article was seldom included in the manuscript. The curiosity to develop NDDSs of antidiabetic drugs with special attention to the nanoparticulate system followed by microparticulate and lipid-based system is found to emerge gradually to overcome the problems associated with the conventional dosage forms and to win the confidence of end users towards the higher acceptability. In the current scientific panorama when the area of novel drug delivery system has been recognized for its palpable benefits, unique potential of providing physical stability, sustained and site-specific drug delivery for a scheduled period of time can open new vistas for precise, safe and quality treatment of DM.

Anti-diabetic formulations of Nāga bhasma (lead calx): A brief review

PubMed Central

Rajput, Dhirajsingh; Patgiri, B. J.; Galib, R; Prajapati, P. K.

2013-01-01

Introduction: Ayurvedic formulations usually contain ingredients of herbal, mineral, metal or animal in origin. Nāga bhasma (lead calx) is a potent metallic formulation mainly indicated in the treatment of Prameha (~diabetes). Until date, no published information is available in compiled form on the formulations containing Nāga bhasma as an ingredient, their dose and indications. Therefore, in the present study, an attempt has been made to compile various formulations of Nāga bhasma indicated in treating Prameha. Aim: The present work aims to collect information on various formulations of Nāga bhasma mainly indicated in treating Prameha and to elaborate the safety and efficacy of Nāga bhasma as a Pramehaghna (antidiabetic) drug. Materials and Methods Critical review of formulations of Nāga bhasma is compiled from various Ayurvedic texts and the therapeutic efficacy of Nāga bhasma is discussed on the basis of available data. Result and Conclusion: Antidiabetic formulations of Nāga bhasma were discovered around 12th century CE. There are 44 formulations of Nāga bhasma mainly indicated for Prameha. Haridrā (Curcuma longa Linn), Āmalakī (Emblica officinalis), Guḍūci (Tinospora cordifolia) and Madhu (honey) enhance the antidiabetic action of Nāga bhasma and also help to prevent diabetic complications as well as any untoward effects of Nāga bhasma. On the basis of the reviewed research, it is concluded that Nāga bhasma possesses significant antidiabetic property. PMID:25161332

Anti-diabetic medications and risk of primary liver cancer in persons with type II diabetes.

PubMed

Hagberg, K W; McGlynn, K A; Sahasrabuddhe, V V; Jick, S

2014-10-28

Type II diabetes increases liver cancer risk but the risk may be mitigated by anti-diabetic medications. However, choice of medications is correlated with diabetes duration and severity, leading to confounding by indication. To address this association, we conducted a nested case-control study among persons with type II diabetes in the Clinical Practice Research Datalink. Cases had primary liver cancer and controls were matched on age, sex, practice, calendar time, and number of years in the database. Exposure was classified by type and combination of anti-diabetic prescribed and compared to non-use. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. In 305 cases of liver cancer and 1151 controls, there was no association between liver cancer and anti-diabetic medication use compared to non-use (OR=0.74 (95% CI=0.45-1.20) for metformin-only, 1.10 (95% CI=0.66-1.84) for other oral hypoglycaemic (OH)-only, 0.89 (95% CI=0.58-1.37) for metformin+other OH, 1.11 (95% CI=0.60-2.05) for metformin+insulin, 0.81 (95% CI=0.23-2.85) for other OH+insulin, and 0.72 (95% CI=0.18-2.84) for insulin-only). Stratification by duration of diabetes did not alter the results. Use of any anti-diabetic medications in patients with type II diabetes was not associated with liver cancer, though there was a suggestion of a small protective effect for metformin.

Hydroxylamine enhances glucose uptake in C2C12 skeletal muscle cells through the activation of insulin receptor substrate 1.

PubMed

Kimura, Taro; Kato, Eisuke; Machikawa, Tsukasa; Kimura, Shunsuke; Katayama, Shinji; Kawabata, Jun

2014-02-28

Diabetes mellitus is a global disease, and the number of patients with it is increasing. Of various agents for treatment, those that directly act on muscle are currently attracting attention because muscle is one of the main tissues in the human body, and its metabolism is decreased in type II diabetes. In this study, we found that hydroxylamine (HA) enhances glucose uptake in C2C12 myotubes. Analysis of HA's mechanism revealed the involvement of IRS1, PI3K and Akt that is related to the insulin signaling pathway. Further investigation about the activation mechanism of insulin receptor or IRS1 by HA may provide a way to develop a novel anti-diabetic agent alternating to insulin. Copyright © 2014 Elsevier Inc. All rights reserved.

New approach of delivering cytotoxic drugs towards CAIX expressing cells: A concept of dual-target drugs.

PubMed

van Kuijk, Simon J A; Parvathaneni, Nanda Kumar; Niemans, Raymon; van Gisbergen, Marike W; Carta, Fabrizio; Vullo, Daniela; Pastorekova, Silvia; Yaromina, Ala; Supuran, Claudiu T; Dubois, Ludwig J; Winum, Jean-Yves; Lambin, Philippe

2017-02-15

Carbonic anhydrase IX (CAIX) is a hypoxia-regulated and tumor-specific protein that maintains the pH balance of cells. Targeting CAIX might be a valuable approach for specific delivery of cytotoxic drugs, thereby reducing normal tissue side-effects. A series of dual-target compounds were designed and synthesized incorporating a sulfonamide, sulfamide, or sulfamate moiety combined with several different anti-cancer drugs, including the chemotherapeutic agents chlorambucil, tirapazamine, and temozolomide, two Ataxia Telangiectasia and Rad3-related protein inhibitors (ATRi), and the anti-diabetic biguanide agent phenformin. An ATRi derivative (12) was the only compound to show a preferred efficacy in CAIX overexpressing cells versus cells without CAIX expression when combined with radiation. Its efficacy might however not solely depend on binding to CAIX, since all described compounds generally display low activity as carbonic anhydrase inhibitors. The hypothesis that dual-target compounds specifically target CAIX expressing tumor cells was therefore not confirmed. Even though dual-target compounds remain an interesting approach, alternative options should also be investigated as novel treatment strategies. Copyright © 2016 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Obesity and infection: reciprocal causality.

PubMed

Hainer, V; Zamrazilová, H; Kunešová, M; Bendlová, B; Aldhoon-Hainerová, I

2015-01-01

Associations between different infectious agents and obesity have been reported in humans for over thirty years. In many cases, as in nosocomial infections, this relationship reflects the greater susceptibility of obese individuals to infection due to impaired immunity. In such cases, the infection is not related to obesity as a causal factor but represents a complication of obesity. In contrast, several infections have been suggested as potential causal factors in human obesity. However, evidence of a causal linkage to human obesity has only been provided for adenovirus 36 (Adv36). This virus activates lipogenic and proinflammatory pathways in adipose tissue, improves insulin sensitivity, lipid profile and hepatic steatosis. The E4orf1 gene of Adv36 exerts insulin senzitizing effects, but is devoid of its pro-inflammatory modalities. The development of a vaccine to prevent Adv36-induced obesity or the use of E4orf1 as a ligand for novel antidiabetic drugs could open new horizons in the prophylaxis and treatment of obesity and diabetes. More experimental and clinical studies are needed to elucidate the mutual relations between infection and obesity, identify additional infectious agents causing human obesity, as well as define the conditions that predispose obese individuals to specific infections.

Nightmare and Abnormal Dreams: Rare Side Effects of Metformin?

PubMed Central

Yanto, Theo Audi; Kosasih, Felicia Nathania

2018-01-01

Background Metformin is widely known as an antidiabetic agent which has significant gastrointestinal side effects, but nightmares and abnormal dreams as its adverse reactions are not well reported. Case Presentation Herein we present a case of 56-year-old male patient with no known history of recurrent nightmares and sleep disorder, experiencing nightmare and abnormal dreams directly after consumption of 750 mg extended release metformin. He reported his dream as an unpleasant experience which awakened him at night with negative feelings. The nightmare only lasted for a night, but his dreams every night thereafter seemed abnormal. The dreams were vivid and indescribable. The disappearance and occurrence of abnormal dreams ensued soon after the drug was discontinued and rechallenged. The case was assessed using Naranjo Adverse Drug Reaction (ADR) probability scale and resulted as probable causality. Conclusion Metformin might be the underlying cause of nightmare and abnormal dreams in this patient. More studies are needed to confirm the association and causality of this findings. PMID:29581904

Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp).

PubMed

Kalra, Sanjay; Atkin, Stephen; Cervera, Antonio; Das, Ashok Kumar; Demir, Ozgur; Demir, Tevfik; Fariduddin, Md; Vo, Khoa Tuan; Ku, Bon Jeong; Kumar, Ajay; Latif, Zafar A; Malek, Rachid; Matawaran, Bien J; Mehta, Roopa; Tran, Nam Quang; Panelo, Araceli; Ruder, Sundeep; Saldana, Joel Rodriquez; Shaikh, Khalid A; Shakya, Amit; Shrestha, Dina; Unnikrishnan, A G

2018-05-23

Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long-term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4-5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes.

Inhibition of α-glucosidase and hypoglycemic effect of stilbenes from the Amazonian plant Deguelia rufescens var. urucu (Ducke) A. M. G. Azevedo (Leguminosae).

PubMed

Pereira, Aline C; Arruda, Mara S; da Silva, Ewerton A; da Silva, Milton N; Lemos, Virgínia S; Cortes, Steyner F

2012-01-01

The control of blood glucose levels is critical in the treatment of diabetes mellitus. α-Glucosidase inhibitors are of great importance in reducing hyperglycemia, and plants have provided many of these agents. The present study aimed at investigating the effect of two stilbenes, lonchocarpene and 3,5-dimethoxy-4'-O-prenyl-trans-stilbene (DPS), isolated from the Amazonian plant Deguelia rufescens var. urucu, on α-glucosidase activity and on mice postprandial hyperglycemia. Lonchocarpene and DPS inhibited α-glucosidase in vitro, with pIC(50) values of 5.68 ± 0.12 and 5.73 ± 0.08, respectively. In addition, when given orally, DPS produced a significant reduction of hyperglycemia induced by an oral tolerance test, while lonchocarpene did not. Data suggest that DPS may have a potential use as an antidiabetic drug. © Georg Thieme Verlag KG Stuttgart · New York.

Preparation and evaluation of a controlled drug release of repaglinide through matrix pellets: in vitro and in vivo studies.

PubMed

Tavakoli, Naser; Minaiyan, Mohsen; Tabbakhian, Majid; Pendar, Yaqub

2014-01-01

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1 h. Designing a controlled release dosage form of the drug is required to maintain its therapeutic blood level and to eliminate its adverse effects, particularly the hypoglycaemia. Repaglinide sustained release matrix pellets consisting of Avicel, lactose and different polymers were prepared using extrusion-spheronisation method. The effect of different formulation components on in vitro drug release were evaluated using USP apparatus (paddle) for 12 h in phosphate buffer. The optimised formulation was orally administrated to normal and STZ induced diabetic rats. Most pellet formulations had acceptable physical properties with regard to size distribution, flowability and friability. Repaglinide pellets comprising Avicel 50%, lactose 47% and SLS 1% were released 94% of its drug content after 12 h. The optimised formulation was able to decrease blood glucose level in normal rats and those with diabetes throughout 8-12 h.

Effect of N-benzoyl-D-phenylalanine, a new potential oral antidiabetic agent, in neonatal streptozotocin-induced diabetes in rats.

PubMed

Pari, Leelavinothan; Ashokkumar, Natarajan

2005-01-01

The present investigation was undertaken to study the effect of treatment with D-phenylalanine derivative and metformin in neonatal streptozotocin (nSTZ)-induced non-insulin-dependent diabetes mellitus (NIDDM) in rats. To induce NIDDM, a single dose injection of streptozotozin (STZ) (100 mg kg(-1); ip) was given to 2-day-old rats. After 10-12 weeks, rats weighing above 150 g were selected for screening in NIDDM model. They were checked for fasting blood glucose levels to conform the status of NIDDM. D-phenylalanine derivative (50, 100 and 200 mg kg(-1)) was administered per os (po) for 6 weeks to the rats with confirmed diabetes. A group of diabetic rats was also maintained and this group received metformin as comparative drug. Significant decrease in blood glucose with significant increase in plasma insulin was observed in group receiving 100 mg of D-phenylalanine derivative plus 500 mg of metformin.

Selective Modulators of PPAR-γ Activity: Molecular Aspects Related to Obesity and Side-Effects

PubMed Central

Zhang, Fang; Lavan, Brian E.; Gregoire, Francine M.

2007-01-01

Peroxisome proliferator-activated receptor γ (PPAR-γ) is a key regulator of lipid metabolism and energy balance implicated in the development of insulin resistance and obesity. The identification of putative natural and synthetic ligands and activators of PPAR-γ has helped to unravel the molecular basis of its function, including molecular details regarding ligand binding, conformational changes of the receptor, and cofactor binding, leading to the emergence of the concept of selective PPAR-γ modulators (SPPARγMs). SPPARγMs bind in distinct manners to the ligand-binding pocket of PPAR-γ, leading to alternative receptor conformations, differential cofactor recruitment/displacement, differential gene expression, and ultimately differential biological responses. Based on this concept, new and improved antidiabetic agents for the treatment of diabetes are in development. This review summarizes the current knowledge on the mechanism of action and biological effects of recently characterized SPPARγMs, including metaglidasen/halofenate, PA-082, and the angiotensin receptor antagonists, recently characterized as a new class of SPPARγMs. PMID:17389769

Study on antidiabetic activity of wheat and barley starch using asymmetrical flow field-flow fractionation coupled with multiangle light scattering.

PubMed

Dou, Haiyang; Zhou, Bing; Jang, Hae-Dong; Lee, Seungho

2014-05-02

The ability of asymmetrical flow field-flow fractionation (AF4) coupled online with multiangle light scattering (MALS) and refractive index detector (RI) (AF4-MALS-RI) for monitoring of change in molecular conformation of wheat and barley starch during germination process was evaluated. AF4 provides separation of starch molecules based on their hydrodynamic sizes, and MALS yields the molar mass and molecular size (radius of gyration, Rg). In vitro and in vivo anti-hyperglycemic effect of germinated wheat and barley was studied. The relationship between antidiabetic activity and molecular conformation was, for the first time, investigated. The ratio of Rg to the hydrodynamic radius (Rh) and the apparent density were proven to be important parameters as they offer an insight into molecular conformation. Results showed that, when geminated, the apparent density and the antidiabetic activity of barley were significantly increased, suggesting germination makes the molecules more compact which could contribute to enhancement of their antidiabetic activity. The information obtained by AF4-MALS-RI is valuable for understanding of germination mechanism, and thus for developing functional foods. Copyright © 2014 Elsevier B.V. All rights reserved.

Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence

PubMed Central

Kawanami, Daiji; Matoba, Keiichiro; Sango, Kazunori; Utsunomiya, Kazunori

2016-01-01

An increase in the rates of morbidity and mortality associated with diabetic complications is a global concern. Glycemic control is important to prevent the development and progression of diabetic complications. Various classes of anti-diabetic agents are currently available, and their pleiotropic effects on diabetic complications have been investigated. Incretin-based therapies such as dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are now widely used in the treatment of patients with type 2 diabetes. A series of experimental studies showed that incretin-based therapies have beneficial effects on diabetic complications, independent of their glucose-lowering abilities, which are mediated by anti-inflammatory and anti-oxidative stress properties. Based on these findings, clinical studies to assess the effects of DPP-4 inhibitors and GLP-1RA on diabetic microvascular and macrovascular complications have been performed. Several but not all studies have provided evidence to support the beneficial effects of incretin-based therapies on diabetic complications in patients with type 2 diabetes. We herein discuss the experimental and clinical evidence of incretin-based therapy for diabetic complications. PMID:27483245

Antidiabetic and Antihyperlipidemic Effects of Ethanol Extract of Rosa canina L. fruit on Diabetic Rats: An Experimental Study With Histopathological Evaluations.

PubMed

Taghizadeh, Mohsen; Rashidi, Ali Akbar; Taherian, Ali Akbar; Vakili, Zarichehr; Sajad Sajadian, Mohammad; Ghardashi, Mostafa

2016-10-01

Rosa canina L. (Rosaceae) has been traditionally used as a medicinal plant. This study was undertaken to evaluate the antidiabetic and antihyperlipidemic effects of Rosa canina fruit extract in streptozotocin induced diabetic rats. The results showed oral administration of Rosa canina fruit extract significantly ameliorated the high levels of blood glucose compared with the control group. Serum triglyceride levels significantly decreased by the administration of Rosa canina extract compared with control. Histopathological examinations showed that the Rosa canina extract improved islets necrotic and regenerated pancreatic islet cells. Rosa canina extract has the antihyperglycemic and antihyperlipidemic effects in streptozotocin-induced diabetic rats. © The Author(s) 2015.

Enzyme inhibitory and radical scavenging effects of some antidiabetic plants of Turkey

PubMed Central

Orhan, Nilüfer; Hoçbaç, Sanem; Orhan, Didem Deliorman; Asian, Mustafa; Ergun, Fatma

2014-01-01

Objective(s): Ethnopharmacological field surveys demonstrated that many plants, such as Gentiana olivieri, Helichrysum graveolens, Helichrysum plicatum ssp. plicatum, Juniperus oxycedrus ssp. oxycedrus, Juniperus communis var. saxatilis, Viscum album (ssp. album, ssp. austriacum), are used as traditional medicine for diabetes in different regions of Anatolia. The present study was designed to evaluate the in vitro antidiabetic effects of some selected plants, tested in animal models recently. Materials and Methods: α-glucosidase and α-amylase enzyme inhibitory effects of the plant extracts were investigated and Acarbose was used as a reference drug. Additionally, radical scavenging capacities were determined using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) ABTS radical cation scavenging assay and total phenolic content of the extracts were evaluated using Folin Ciocalteu method. Results: H. graveolens ethanol extract exhibited the highest inhibitory activity (55.7 % ± 2.2) on α-amylase enzyme. Additionally, J. oxycedrus hydro-alcoholic leaf extract had potent α-amylase inhibitory effect, while the hydro-alcoholic extract of J. communis fruit showed the highest α-glucosidase inhibitory activity (IC50: 4.4 μg/ml). Conclusion: Results indicated that, antidiabetic effect of hydro-alcoholic extracts of H. graveolens capitulums, J. communis fruit and J. oxycedrus leaf might arise from inhibition of digestive enzymes. PMID:25140204

Canagliflozin-current status in the treatment of type 2 diabetes mellitus with focus on clinical trial data

PubMed Central

Bhatia, Jagriti; Gamad, Nanda; Bharti, Saurabh; Arya, Dharamvir Singh

2014-01-01

Canagliflozin (CFZ) is a member of new class of glucose lowering agents, sodium-glucose co-transporter (SGLT) inhibitors, which got approval by food and drug administration. It has insulin independent action by blocking the transporter protein SGLT2 in the kidneys, resulting in urinary glucose excretion and reduction in blood glucose levels. In clinical trials, CFZ significantly decreased HbA1c level when administered either as monotherapy or as combined therapy with other anti-diabetic drugs. Intriguingly, it showed additional benefits like weight reduction and lowering of blood pressure. The commonly observed side effects were urinary and genital infections. It has exhibited favorable pharmacokinetic and pharmacodynamic profiles even in patients with renal and hepatic damage. Hence, this review purports to outline CFZ as a newer beneficial drug for type 2 diabetes mellitus. PMID:24936262

Ellagic Acid: A Logical Lead for Drug Development?

PubMed

Shakeri, Abolfazl; Zirak, Mohammad Reza; Sahebkar, Amirhossein

2018-01-01

Naturally occurring polyphenols are the subject of increasing attention due to their potent antioxidant activity and their marked effects on the prevention of various oxidative stress-associated diseases such as cancer. Ellagic acid (EA) is an herbal polyphenol that is structurally a condensed dimer of gallic acid. This review aims to provide a comprehensive and updated overview on the biological activities of EA and potential therapeutic applications. EA is found in fruits and nuts, either in the combined form with hexahydroxydiphenic acid or in the bound form (ellagitannins). EA exhibits many biological properties such as antioxidant, anti-diabetic, anticancer and apoptosis-inducing activities. These biological and pharmacological properties are relevant to the treatment of several human diseases. Owing to its multiple mechanisms of action, EA represents a potential therapeutic agent against human diseases particularly cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Analgesic and antipyretic activities of Momordica charantia Linn. fruits

PubMed Central

Patel, Roshan; Mahobia, Naveen; Upwar, Nitin; Waseem, Naheed; Talaviya, Hetal; Patel, Zalak

2010-01-01

Plant Momordica charantia Linn. belongs to family Cucurbitaceae. It is known as bitter gourd in English and karela in Hindi. Earlier claims show that the plant is used in stomachic ailments as a carminative tonic; as an antipyretic and antidiabetic agent; and in rheumatoid arthritis and gout. The fruit has been claimed to contain charantin, steroidal saponin, momordium, carbohydrates, mineral matters, ascorbic acid, alkaloids, glucosides, etc. The ethanolic extract of the fruit showed the presence of alkaloids, tannins, glycosides, steroids, proteins, and carbohydrates. The present study was carried out using acetic acid-induced writhing and tail-immersion tests in mice, while yeast-induced pyrexia in rats. The ethanolic extracts (250 and 500 mg/kg, po.) showed an analgesic and antipyretic effect, which was significantly higher than that in the control rats. The observed pharmacological activities provide the scientific basis to support traditional claims as well as explore some new and promising leads. PMID:22247882

Analgesic and antipyretic activities of Momordica charantia Linn. fruits.

PubMed

Patel, Roshan; Mahobia, Naveen; Upwar, Nitin; Waseem, Naheed; Talaviya, Hetal; Patel, Zalak

2010-10-01

Plant Momordica charantia Linn. belongs to family Cucurbitaceae. It is known as bitter gourd in English and karela in Hindi. Earlier claims show that the plant is used in stomachic ailments as a carminative tonic; as an antipyretic and antidiabetic agent; and in rheumatoid arthritis and gout. The fruit has been claimed to contain charantin, steroidal saponin, momordium, carbohydrates, mineral matters, ascorbic acid, alkaloids, glucosides, etc. The ethanolic extract of the fruit showed the presence of alkaloids, tannins, glycosides, steroids, proteins, and carbohydrates. The present study was carried out using acetic acid-induced writhing and tail-immersion tests in mice, while yeast-induced pyrexia in rats. The ethanolic extracts (250 and 500 mg/kg, po.) showed an analgesic and antipyretic effect, which was significantly higher than that in the control rats. The observed pharmacological activities provide the scientific basis to support traditional claims as well as explore some new and promising leads.

[Limitations of insulin-dependent drugs in the treatment of type 2 diabetes mellitus].

PubMed

Valerón, Pino Fuente; de Pablos-Velasco, Pedro L

2013-09-01

In this study, we review the efficacy and safety limitations of insulin-dependent oral antidiabetic agents. In terms of efficiency, the main drawback of metformin, sulfonylureas, gliptins and -to a lesser extent-glitazones is durability. No drug per se is able to maintain stable blood glucose control for years. Metformin, sulfonylureas and gliptins have demonstrated safety. Experience with the first two drug groups is more extensive. The main adverse effect of metformin is gastrointestinal discomfort. Major concerns related to the use of sulfonylureas are hypoglycemia and weight gain. The use of pioglitazone has been associated with an increased risk of bladder cancer, edema, heart failure, weight gain, and distal bone fractures in postmenopausal women. The most common adverse reactions associated with glucagon-like peptide-1 agonists are gastrointestinal discomfort that sometimes leads to treatment discontinuation. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Diabetes mellitus.

PubMed

Ahmed, Intekhab; Goldstein, Barry

2006-01-01

Dermatologic problems are common in diabetes, with approximately 30% of patients experiencing some cutaneous involvement during the course of their illness. Skin manifestations generally appear during the course of the disease in patients known to have diabetes, but they may also be the first presenting sign of diabetes or even precede the diagnosis by many years. The skin involvement can be autoimmune in nature, such as acanthosis nigricans, necrobiosis lipoidica, diabetic dermopathy, scleredema, and granuloma annulare, or infectious in the form of erythrasma, necrotizing fasciitis, and mucormycosis. Pharmacologic management of diabetes, in addition, can also result in skin changes, such as lipoatrophy and lipohypertrophy, at the site of injection of insulin, and oral antidiabetic agents can cause multiple skin reactions as adverse effects. The management of these cutaneous manifestations is tailored according to the underlying pathophysiology, but a tight control of blood glucose is a prerequisite in all management strategies.

Sodium glucose co-transporter 2 (SGLT2) inhibitors: novel antidiabetic agents.

PubMed

Washburn, William N

2012-05-01

Maintenance of glucose homeostasis in healthy individuals involves SGLT2 (sodium glucose co-transporter 2)-mediated recovery of glucose from the glomerular filtrate which otherwise would be excreted in urine. Clinical studies indicate that SGLT2 inhibitors provide an insulin-independent means to reduce the hyperglycemia that is the hallmark of type 2 diabetes mellitus (T2DM) with minimal risk of hypoglycemia. The pharmacophore common to the SGLT2 inhibitors currently in development is a diarylmethane C-glucoside which is discussed in this review. The focus is how this pharmacophore was further modified as inferred from the patents publishing from 2009 to 2011. The emphasis is on the strategy that each group employed to circumvent the constraints imposed by prior art and how the resulting SGLT2 potency and selectivity versus SGLT1 compared with that of the lead clinical compound dapagliflozin. SGLT2 inhibitors offer a new fundamentally different approach for treatment of diabetes. To date, the clinical results suggest that for non-renally impaired patients this class of inhibitors could be safely used at any stage of T2DM either alone or in combination with other marketed antidiabetic medications.

Antidiabetic potential of Caesalpinia sumatrana, a medicinal herbs traditionally used by local tribe in East Kalimantan

NASA Astrophysics Data System (ADS)

Wicaksono, D. A.; Rosamah, E.; Kusuma, I. W.

2018-04-01

The aims of the research was to analyze the content of phytochemicals, to examine the antioxidant and antidiabeticpotentials of n-hexane, chloroform, ethyl acetate, and ethanol extracts of Caesalpinia sumatrana. Method to measure antioxidant capacity of sample involves the use of the free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH) which is widely used to test the ability of compounds to act as free radical. Analysis the potential of antidiabeticactivity of the extracts was determined by α-glucosidase and α-amylase inhibitory assay. Of all extracts obtained by successive maceration, ethanol maceration gave the highest extract by 2.63% of extract on the dry weigh basis. The result of phytochemicals showed that all extracts contain alkaloid and flavonoid. The highest antioxidant activity was 82.32% with IC50 value of 5.00 µg/ml obtained by ethanol extract. The results of enzyme inhibitory assay of α-glucosidase showed that ethanol extract of C. sumatrana had IC50 value 17.16 µg/mL to inhibit ɑ-glucosidase activity and IC50 value 16.78 µg/mL for ɑ-amylase. The present result displayed potential of the plant to be developed as natural antidiabetic and antioxidant agents.

Progression to insulin for patients with diabetes mellitus on dual oral antidiabetic therapy using the US Department of Defense Database.

PubMed

Rascati, K; Richards, K; Lopez, D; Cheng, L-I; Wilson, J

2013-10-01

To compare 'progression to insulin' for three cohorts on oral antidiabetic medication combinations: metformin/sulphonylurea (Met/SU), metformin/thiazolidinedione (Met/TZD) and sulphonylurea/thiazolidinedione (SU/TZD). Retrospective cohort analysis design was used. The subjects were US nationwide members of military and their families. A total of 5608 patients who were on antidiabetic monotherapy for at least 1 year before adding a second agent to their medication regimen between October 2001 and September 2008 participated in this study. Mean age ranged from 64 to 71 years among the cohorts. Cox regression compared the progression to insulin, adjusting for demographics, months of follow-up and co-morbidities [measured with Chronic Disease Score (CDS)]. By the end of the 2- to 6-year follow-up period, 14.3% of the Met/TZD cohort, 23.6% of the Met/SU cohort and 28.2% of the SU/TZD cohort had insulin added to their regimen. Those in the Met/SU cohort had a 1.8 times higher probability of progression to insulin than those in the Met/TZD cohort [odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.51-2.14), and those in the SU/TZD cohort had a 2.5 times higher probability of progression to insulin than those in the Met/TZD cohort (OR = 2.51, 95% CI = 2.04-3.08). When sensitizers were paired (Met/TZD), a lower percentage of patients progressed to insulin during the study period, as opposed to patients who used a combination of a secretagogue with a sensitizer (SU/TZD or Met/SU). © 2013 John Wiley & Sons Ltd.

[New antidiabetic medications: at the dawn of a revolution? New therapeutic options for type 2 diabetes are challenged for cardiovascular disease prevention].

PubMed

Crenier, L

Despite advances in the management of type 2 diabetes, cardiovascular disease remains a major concern. Large glycemic control intervention trials have taught us that at least ten years are needed to see the benefits of a conventional diabetes therapy on morbidity and mortality of cardiovascular disease. Following the controversy about rosiglitazone in 2008, the FDA required cardiovascular safety data for all new antidiabetic medications and early studies to comply with this regulation are now published. They showed first the cardiovascular neutrality of gliptins, a result not really surprising for a median follow-up of less than 3 years. However, EMPA-REG-OUTCOME and LEADER studies were very surprising. Both were performed in type 2 diabetic patients with a history of cardiovascular disease. In the f irst of these studies, empaglif lozine prescribed over the usual antidiabetic treatment reduced by 14 % (P ⟨ 0,04) the composite primary endpoint (nonfatal myocardial infarction or nonfatal stroke or cardiovascular death), and this mainly through a reduction in cardiovascular mortality by 38 % (P ⟨ 0,001). Thereafter, LEADER has similarly shown that liraglutide reduced by 13 % the same primary endpoint (P = 0,01) along with a 22 % reduction in cardiovascular mortality (P = 0,007). In both cases, the median follow-up was less than four years. In conclusion, these two studies demonstrate that powerful, although still unknown mechanisms for cardiovascular protection exist. These mechanisms are able to improve survival by a glucose independent way, in a very high risk diabetic population already heavily treated by sartans/ACE inhibitors, statins and antiplatelet agents.

Randomized and double-blinded pilot clinical study of the safety and anti-diabetic efficacy of the Rauvolfia-Citrus tea, as used in Nigerian traditional medicine.

PubMed

Campbell-Tofte, Joan I A; Mølgaard, Per; Josefsen, Knud; Abdallah, Zostam; Hansen, Steen Honoré; Cornett, Claus; Mu, Huiling; Richter, Erik A; Petersen, Henning Willads; Nørregaard, Jens Christian; Winther, Kaj

2011-01-27

The aim of this randomized and double blinded pilot clinical trial was to investigate the anti-diabetic efficacy of the Rauvolfia-Citrus (RC) tea in humans. We have earlier shown that a combination of calorie-restriction and chronic administration of the RC tea to the genetic diabetic (BKS-db) mice resulted in the normalization of blood sugar, reduction in lipid accumulated in the mice eyes and prevention of the degeneration of the otherwise brittle BKS-db pancreas. The tea is made by boiling foliage of Rauvolfia vomitoria and fruits of Citrus aurantium and is used to treat diabetes in Nigerian folk medicine. The RC tea was produced using the Nigerian traditional recipe and tested in the traditional dosage on 23 Danish type 2 diabetes (T2D) patients. The participants were divided into two equivalent groups after stratification by sex, age and BMI, in a 4-month double-blinded, placebo-controlled and randomized clinical trial. Most of the study subjects (19/23) were using oral anti-diabetic agents (OADs). Mean disease duration was 6±4.6 years, mean age was 64±7 years and mean BMI was 28.7±3.8 kg/m(2). Prior to starting the treatment, the participants received individual dietician consultations. At the end of the 4-month treatment period, the treated group showed an 11% decrease in 2-h postprandial plasma glucose relative to the 3% increase in the placebo group (p=0.004). The improvement in blood glucose clearance with RC tea treatment was reflected in a 6% reduction in HbA(1c) (p=0.02) and in a 10% reduction in fasting plasma glucose (p=0.02), when comparing the post 4-month treatment to pre-treatment baseline values. Though the basal levels of phosphorylated acetyl CoA carboxylase enzyme in skeletal muscle were significantly reduced in the treated group (p=0.04), as compared to the placebo, only the pattern of reductions in the tissue fatty acids (FAs) differed in the two groups. While all types of FAs were reduced in placebo, only saturated (SFA) and monounsaturated (MUFA) FAs were reduced with treatment. Interestingly, a modest increase in the polyunsaturated FAs fraction was observed in the RC treated group. In addition, the reduction in SFA and MUFA with RC tea treatment came solely from the triglyceride fractions, as there was an increase in the skeletal muscle phospholipids. Chronic administration of the RC tea to overweight T2D on OADs caused significant improvements in markers of glycaemic control and modifications to the fatty acid profile of skeletal muscle, without adverse effects or hypoglycaemia. Further exploration of the anti-diabetic effects of the RC tea is warranted. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Anti-Diabetic Potential of Noni: The Yin and the Yang.

PubMed

Nerurkar, Pratibha V; Hwang, Phoebe W; Saksa, Erik

2015-09-25

Escalating trends of chronic diseases such as type-2 diabetes (T2D) have sparked a renewed interest in complementary and alternative medicine, including herbal products. Morinda citrifolia (noni) has been used for centuries by Pacific Islanders to treat various ailments. Commercial noni fruit juice has been marketed as a dietary supplement since 1996. In 2003, the European Commission approved Tahitian noni juice as a novel food by the Health and Consumer Protection Directorate General. Among noni's several health benefits, others and we have demonstrated the anti-diabetic effects of fermented noni fruit juice in animal models. Unfortunately, noni's exciting journey from Polynesian medicine to the research bench does not reach its final destination of successful clinical outcomes when translated into commercial products. Noni products are perceived to be safe due to their "natural" origin. However, inadequate evidence regarding bioactive compounds, molecular targets, mechanism of action, pharmacokinetics, long-term safety, effective dosages, and/or unanticipated side effects are major roadblocks to successful translation "from bench side to bedside". In this review we summarize the anti-diabetic potential of noni, differences between traditional and modern use of noni, along with beneficial clinical studies of noni products and challenges in clinical translation of noni's health benefits.

Cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and by stimulating insulin secretion in vitro.

PubMed

Hafizur, Rahman M; Hameed, Abdul; Shukrana, Mishkat; Raza, Sayed Ali; Chishti, Sidra; Kabir, Nurul; Siddiqui, Rehan A

2015-02-15

Although the anti-diabetic activity of cinnamic acid, a pure compound from cinnamon, has been reported but its mechanism(s) is not yet clear. The present study was designed to explore the possible mechanism(s) of anti-diabetic activity of cinnamic acid in in vitro and in vivo non-obese type 2 diabetic rats. Non-obese type 2 diabetes was developed by injecting 90 mg/kg streptozotocin in 2-day-old Wistar pups. Cinnamic acid and cinnamaldehyde were administered orally to diabetic rats for assessing acute blood glucose lowering effect and improvement of glucose tolerance. Additionally, insulin secretory activity of cinnamic acid and cinnamaldehyde was evaluated in isolated mice islets. Cinnamic acid, but not cinnamaldehyde, decreased blood glucose levels in diabetic rats in a time- and dose-dependent manner. Oral administration of cinnamic acid with 5 and 10 mg/kg doses to diabetic rats improved glucose tolerance in a dose-dependent manner. The improvement by 10 mg/kg cinnamic acid was comparable to that of standard drug glibenclamide (5 mg/kg). Further in vitro studies showed that cinnamaldehyde has little or no effect on glucose-stimulated insulin secretion; however, cinnamic acid significantly enhanced glucose-stimulated insulin secretion in isolated islets. In conclusion, it can be said that cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and stimulating insulin secretion in vitro. Copyright © 2015 Elsevier GmbH. All rights reserved.

Antidiabetic and Antioxidant Effects and Phytochemicals of Mulberry Fruit (Morus alba L.) Polyphenol Enhanced Extract

PubMed Central

Wang, Yihai; Xiang, Limin; Wang, Chunhua; Tang, Chao; He, Xiangjiu

2013-01-01

The antidiabetic and antioxidant activities of the ethyl acetate-soluble extract (MFE) of mulberry fruit (Morus alba L.) were investigated. In vitro, MFE showed potent α-glucosidase inhibitory activity and radical-scavenging activities against DPPH and superoxide anion radicals. In vivo, MFE could significantly decrease fasting blood glucose (FBG) and glycosylated serum protein (GSP), and increase antioxidant enzymatic activities (SOD, CAT, GSH-Px) in streptozotocin (STZ)-induced diabetic mice. Bioactivity-guided fractionation of the MFE led to the isolation of 25 phenolic compounds, and their structures were identified on the basis of MS and NMR data. All the 25 compounds were isolated from mulberry fruit for the first time. Also, the α-glucosidase inhibitory activity and antioxidant activity of the phenolics were evaluated. Potent α-glucosidase inhibitory and radical-scavenging activities of these phenolics suggested that they may be partially responsible for the antidiabetic and antioxidant activities of mulberry fruit. PMID:23936259

In Vitro Antidiabetic Effects and Antioxidant Potential of Cassia nemophila Pods

PubMed Central

Rehman, Gauhar; Hamayun, Muhammad; Ul Islam, Saif; Arshad, Saba; Zaman, Khair; Ahmad, Ayaz; Shehzad, Adeeb; Hussain, Anwar

2018-01-01

The antidiabetic and antioxidant potential of ethanolic extract of Cassia nemophila pod (EECNP) was evaluated by three in vitro assays, including yeast glucose uptake assay, glucose adsorption assay, and DPPH radical scavenging activity. The result revealed that the extracts have enhanced the uptake of glucose through the plasma membrane of yeast cells. A linear increase in glucose uptake by yeast cells was noticed with gradual increase in the concentration of the test samples. Moreover, the adsorption capacity of the EECNP was directly proportional to the molar concentration of glucose. Also, the DPPH radical scavenging capacity of the extract was increased to a maximum value of 43.3% at 80 μg/ml, which was then decreased to 41.9% at 100 μg/ml. From the results, it was concluded that EECNP possess good antidiabetic and antioxidant properties as shown by in vitro assays. PMID:29607313

Antidiabetic and antioxidant effects and phytochemicals of mulberry fruit (Morus alba L.) polyphenol enhanced extract.

PubMed

Wang, Yihai; Xiang, Limin; Wang, Chunhua; Tang, Chao; He, Xiangjiu

2013-01-01

The antidiabetic and antioxidant activities of the ethyl acetate-soluble extract (MFE) of mulberry fruit (Morus alba L.) were investigated. In vitro, MFE showed potent α-glucosidase inhibitory activity and radical-scavenging activities against DPPH and superoxide anion radicals. In vivo, MFE could significantly decrease fasting blood glucose (FBG) and glycosylated serum protein (GSP), and increase antioxidant enzymatic activities (SOD, CAT, GSH-Px) in streptozotocin (STZ)-induced diabetic mice. Bioactivity-guided fractionation of the MFE led to the isolation of 25 phenolic compounds, and their structures were identified on the basis of MS and NMR data. All the 25 compounds were isolated from mulberry fruit for the first time. Also, the α-glucosidase inhibitory activity and antioxidant activity of the phenolics were evaluated. Potent α-glucosidase inhibitory and radical-scavenging activities of these phenolics suggested that they may be partially responsible for the antidiabetic and antioxidant activities of mulberry fruit.

Antiinflammatory, analgesic and hypoglycemic effects of Mangifera indica Linn. (Anacardiaceae) stem-bark aqueous extract.

PubMed

Ojewole, J A O

2005-10-01

Previous studies in our laboratories and elsewhere have shown that some members of Anacardiaceae family possess antiinflammatory, analgesic and hypoglycemic effects in man and mammalian experimental animals. The present study was, therefore, undertaken to examine the antiinflammatory, analgesic and antidiabetic properties of the stem-bark aqueous extract of Mangifera indica Linn., M. indica a member of the Anacardiaceae family, in rats and mice. The stem-bark powder of M. indica was Soxhlet extracted with distilled water and used. The analgesic effect of the plant's extract was evaluated by the hot-plate and acetic acid test models of pain in mice, while the antiinflammatory and antidiabetic effects of the stem-bark extract were investigated in rats, using fresh egg albumin-induced paw edema, and streptozotocin (STZ)-induced diabetes mellitus, respectively. Morphine (MPN, 10 mg/kg i.p.), diclofenac (DIC, 100 mg/kg i.p.), and chlorpropamide (250 mg/kg p.o.) were used respectively as reference analgesic, antiinflammatory, and hypoglycemic agents for comparison. M. indica stem-bark aqueous extract (MIE, 50-800 mg/kg i.p.) produced dose-dependent and significant (p<0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain stimuli in mice. MIE (50-800 mg/kg i.p.) also significantly (p<0.05-0.001) inhibited fresh egg albumin-induced paw edema, and caused significant (p<0.05-0.001) hypoglycemic effects in rats. It is suggested that the analgesic effects of MIE (50-800 mg/kg i.p.) may be peripherally and centrally mediated. The different chemical constituents of the plant, especially the polyphenolics, flavonoids, triterpenoids, mangiferin, and other chemical compounds present in the plant may be involved in the observed antiinflammatory, analgesic, and hypoglycemic effects of the plant's extract. However, the results of this experimental animal study lend pharmacological credence to the suggested folkloric uses of the plant in the management and control of painful, arthritic and other inflammatory conditions, as well as in the management of adult-onset type 2 diabetes mellitus in some rural African communities. (c) 2005 Prous Science. All rights reserved.

Selective speciation improves efficacy and lowers toxicity of platinum anticancer and vanadium antidiabetic drugs.

PubMed

Doucette, Kaitlin A; Hassell, Kelly N; Crans, Debbie C

2016-12-01

Improving efficacy and lowering resistance to metal-based drugs can be addressed by consideration of the coordination complex speciation and key reactions important to vanadium antidiabetic drugs or platinum anticancer drugs under biological conditions. The methods of analyses vary depending on the specific metal ion chemistry. The vanadium compounds interconvert readily, whereas the reactions of the platinum compounds are much slower and thus much easier to study. However, the vanadium species are readily differentiated due to vanadium complexes differing in color. For both vanadium and platinum systems, understanding the processes as the compounds, Lipoplatin and Satraplatin, enter cells is needed to better combat the disease; there are many cellular metabolites, which may affect processing and thus the efficacy of the drugs. Examples of two formulations of platinum compounds illustrate how changing the chemistry of the platinum will result in less toxic and better tolerated drugs. The consequence of the much lower toxicity of the drug, can be readily realized because cisplatin administration requires hospital stay whereas Lipoplatin can be done in an outpatient manner. Similarly, the properties of Satraplatin allow for development of an oral drug. These forms of platinum demonstrate that the direct consequence of more selective speciation is lower side effects and cheaper administration of the anticancer agent. Therefore we urge that as the community goes forward in development of new drugs, control of speciation chemistry will be considered as one of the key strategies in the future development of anticancer drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

Agreement between self-report and prescription data in medical records for pregnant women.

PubMed

Sarangarm, Preeyaporn; Young, Bonnie; Rayburn, William; Jaiswal, Pallavi; Dodd, Melanie; Phelan, Sharon; Bakhireva, Ludmila

2012-03-01

BACKGROUND Clinical teratology studies often rely on patient reports of medication use in pregnancy with or without other sources of information. Electronic medical records (EMRs), administrative databases, pharmacy dispensing records, drug registries, and patients' self-reports are all widely used sources of information to assess potential teratogenic effect of medications. The objective of this study was to assess comparability of self-reported and prescription medication data in EMRs for the most common therapeutic classes. METHODS The study population included 404 pregnant women prospectively recruited from five prenatal care clinics affiliated with the University of New Mexico. Self-reported information on prescription medications taken since the last menstrual period (LMP) was obtained by semistructured interviews in either English or Spanish. For validation purposes, EMRs were reviewed to abstract information on medications prescribed between the LMP and the date of the interview. Agreement was estimated by calculating a kappa (κ) coefficient, sensitivity, and specificity. RESULTS In this sample of socially-disadvantaged (i.e., 67.9% high school education or less, 48.5% no health insurance), predominantly Latina (80.4%) pregnant women, antibiotics and antidiabetic agents were the most prevalent therapeutic classes. The agreement between the two sources substantially varied by therapeutic class, with the highest level of agreement seen among antidiabetic and thyroid medications (κ ≥0.8) and the lowest among opioid analgesics (κ = 0.35). CONCLUSIONS Results indicate a high concordance between self-report and prescription data for therapeutic classes used chronically, while poor agreement was observed for medications used intermittently, on an 'as needed" basis, or in short courses. Copyright © 2012 Wiley Periodicals, Inc.

Treating Diet-Induced Diabetes and Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells and Antidiabetic Drugs

PubMed Central

Bruin, Jennifer E.; Saber, Nelly; Braun, Natalie; Fox, Jessica K.; Mojibian, Majid; Asadi, Ali; Drohan, Campbell; O’Dwyer, Shannon; Rosman-Balzer, Diana S.; Swiss, Victoria A.; Rezania, Alireza; Kieffer, Timothy J.

2015-01-01

Summary Human embryonic stem cell (hESC)-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD) feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs. PMID:25801507

Effects of commonly used antidiabetic drugs on antioxidant enzymes and liver function test markers in type 2 diabetes mellitus subjects - pilot study.

PubMed

Ghadge, A; Harke, S; Khadke, S; Diwan, A; Pankaj, M; Kulkarni, O; Ranjekar, P; Harsulkar, A; Kuvalekar, A A

2015-09-01

The present study analyzed the effects of antidiabetic drugs on antioxidant enzymes and liver function test (LFT) markers and their association with homeostatic model assessment of insulin resistance (HOMA-IR) in type 2 diabetic subjects. We assessed healthy and diabetic subjects (100 each). Diabetic subjects were divided based on treatment with only metformin, metformin in combination with other antidiabetic drugs and insulin in combination with other antidiabetic drugs. LFT markers, antioxidant status and HOMA-IR were assessed in the subjects. Superoxide dismutase activity was higher (p<0.01) while catalase activity was lower (p<0.01) in the diabetic subjects as compared to controls. Serum glutamate-pyruvate transaminase (SGPT) (p<0.01) and bilirubin (p<0.05) levels were higher in diabetic male subjects while urea (p<0.05) levels were lower and SGPT (p<0.01) levels were higher in diabetic female subjects. In male subjects consuming only metformin, a positive association between HOMA-IR and insulin (p<0.05) was seen. A positive association between HOMA-IR and glucose (p<0.01), insulin (p<0.01), SOD (p<0.01) and SGPT (p<0.05) was seen in males receiving metformin with other drugs. Interestingly, the female subjects on metformin displayed a positive association between HOMA-IR and insulin (p<0.05) only. A positive association of HOMA-IR with glucose (p<0.01) and insulin (p<0.05) was seen in females on metformin in combination with other anti-diabetic drugs. The alterations in the antioxidant enzyme activities and liver function tests are dependent upon the gender and glycemic status of subjects while the variations in correlations of HOMA-IR with antioxidant enzymes, liver function tests and inflammatory markers are dependent on type of treatments. © Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of the Antidiabetic Activity and Chemical Composition of Geranium collinum Root Extracts-Computational and Experimental Investigations.

PubMed

Numonov, Sodik; Edirs, Salamet; Bobakulov, Khayrulla; Qureshi, Muhammad Nasimullah; Bozorov, Khurshed; Sharopov, Farukh; Setzer, William N; Zhao, Haiqing; Habasi, Maidina; Sharofova, Mizhgona; Aisa, Haji Akber

2017-06-13

The root of Geranium collinum Steph is known in Tajik traditional medicine for its hepatoprotective, antioxidant, and anti-inflammatory therapeutic effects. The present study was conducted to evaluate of potential antidiabetic, antioxidant activities, total polyphenolic and flavonoid content from the different extracts (aqueous, aqueous-ethanolic) and individual compounds isolated of the root parts of G. collinum . The 50% aqueous-ethanolic extract possesses potent antidiabetic activity, with IC 50 values of 0.10 μg/mL and 0.09 μg/mL for the enzymes protein-tyrosine phosphatase (1B PTP-1B) and α-glucosidase, respectively. Phytochemical investigations of the 50% aqueous-ethanolic extract of G. collinum , led to the isolation of ten pure compounds identified as 3,3',4,4'-tetra- O -methylellagic acid ( 1 ), 3,3'-di- O -methylellagic acid ( 2 ), quercetin ( 3 ), caffeic acid ( 4 ), (+)-catechin ( 5 ), (-)-epicatechin ( 6 ), (-)-epigallocatechin ( 7 ), gallic acid ( 8 ), β-sitosterol-3- O -β-d-glucopyranoside ( 9 ), and corilagin ( 10 ). Their structures were determined based on 1D and 2D NMR and mass spectrometric analyses. Three isolated compounds exhibited strong inhibitory activity against PTP-1B, with IC 50 values below 0.9 μg/mL, more effective than the positive control (1.46 μg/mL). Molecular docking analysis suggests polyphenolic compounds such as corilagin, catechin and caffeic acid inhibit PTP-1B and β-sitosterol-3- O -β-d-gluco-pyranoside inhibits α-glucosidase. The experimental results suggest that the biological activity of G. collinum is related to its polyphenol contents. The results are also in agreement with computational investigations. Furthermore, the potent antidiabetic activity of the 50% aqueous-ethanolic extract from G. collinum shows promise for its future application in medicine. To the best of our knowledge, we hereby report, for the first time, the antidiabetic activity of G. collinum.

Indexing Natural Products for Their Potential Anti-Diabetic Activity: Filtering and Mapping Discriminative Physicochemical Properties.

PubMed

Zeidan, Mouhammad; Rayan, Mahmoud; Zeidan, Nuha; Falah, Mizied; Rayan, Anwar

2017-09-17

Diabetes mellitus (DM) poses a major health problem, for which there is an unmet need to develop novel drugs. The application of in silico techniques and optimization algorithms is instrumental to achieving this goal. A set of 97 approved anti-diabetic drugs, representing the active domain, and a set of 2892 natural products, representing the inactive domain, were used to construct predictive models and to index anti-diabetic bioactivity. Our recently-developed approach of 'iterative stochastic elimination' was utilized. This article describes a highly discriminative and robust model, with an area under the curve above 0.96. Using the indexing model and a mix ratio of 1:1000 (active/inactive), 65% of the anti-diabetic drugs in the sample were captured in the top 1% of the screened compounds, compared to 1% in the random model. Some of the natural products that scored highly as potential anti-diabetic drug candidates are disclosed. One of those natural products is caffeine, which is noted in the scientific literature as having the capability to decrease blood glucose levels. The other nine phytochemicals await evaluation in a wet lab for their anti-diabetic activity. The indexing model proposed herein is useful for the virtual screening of large chemical databases and for the construction of anti-diabetes focused libraries.

Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese mice.

PubMed

Kim, Myung Sunny; Hur, Haeng Jeon; Kwon, Dae Young; Hwang, Jin-Taek

2012-07-06

Although the flavonoid tangeretin (5, 6, 7, 8, 4'-pentamethoxyflavone) is known to possess beneficial health effects, the anti-diabetic effects and the mechanism of action have not been elucidated. Treatment with 100 μM tangeretin significantly increased the uptake of 2-NBDG in C2C12 myotubes. We also found that AMPK and AS160 were markedly phosphorylated by tangeretin treatment. In addition, pretreatment with an AMPK inhibitor significantly abrogated tangeretin-stimulated AS160 phosphorylation, glucose uptake, and Glut4 translocation from the cytosol to the plasma membrane. Furthermore, disruption of AMPK using siRNA transfection prevented the glucose uptake stimulated by tangeretin. We also examined the anti-diabetic properties of tangeretin in mice on HFD. Administration of HFD plus 200 mg/kg of tangeretin significantly altered weight gain, glucose tolerance, total cholesterol levels, and the secretion of adipocytokines, such as adiponectin, leptin, resistin, IL-6, and MCP-1. Moreover, AMPK was activated by 200 mg/kg of tangeretin in mouse muscle tissue, as expected from the cell system. These results suggest that tangeretin exerts anti-diabetic effects in both cell culture and mouse models, and these effects are necessary for activating AMPK. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The antidiabetic effects of an herbal formula composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin-induced diabetic rats.

PubMed

Hu, Weicheng; Yeo, Jin-Hee; Jiang, Yunyao; Heo, Seong-Il; Wang, Myeong-Hyeon

2013-04-01

A folk prescription consisting of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng has been used in the treatment of diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of the herb formula extract (HFE) composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin (STZ)-induced diabetic rats. The HFE was mixed in the food supply of the healthy and STZ-induced diabetic male Sprague-Dawley rats, and its effects on the body weight, water and food intake, hyperglycemia, hypolipidemic and islet structure were studied. The treatment of the rats with STZ for 6 weeks resulted in marasmus, polydipsia, polyphagia, hyperglycemia and hypoinsulinemia. In addition, the diabetic rats showed an apparent decrease in the insulin immunoreactivity and the number of β-cells in the pancreas. The addition of the HFE to the rats' food supply significantly lowered the serum glucose and the serum triglycerides level and preserved the normal histological appearance of the pancreatic islets. These results indicate that the HEF have a strong antidiabetic potential along with the significant hypoglycemic and hypolipidemic effects, which may be applicable in the pharmaceutical industry.

Diabetes therapies in hemodialysis patients: Dipeptidase-4 inhibitors

PubMed Central

Nakamura, Yuya; Hasegawa, Hitomi; Tsuji, Mayumi; Udaka, Yuko; Mihara, Masatomo; Shimizu, Tatsuo; Inoue, Michiyasu; Goto, Yoshikazu; Gotoh, Hiromichi; Inagaki, Masahiro; Oguchi, Katsuji

2015-01-01

Although several previous studies have been published on the effects of dipeptidase-4 (DPP-4) inhibitors in diabetic hemodialysis (HD) patients, the findings have yet to be reviewed comprehensively. Eyesight failure caused by diabetic retinopathy and aging-related dementia make multiple daily insulin injections difficult for HD patients. Therefore, we reviewed the effects of DPP-4 inhibitors with a focus on oral antidiabetic drugs as a new treatment strategy in HD patients with diabetes. The following 7 DPP-4 inhibitors are available worldwide: sitagliptin, vildagliptin, alogliptin, linagliptin, teneligliptin, anagliptin, and saxagliptin. All of these are administered once daily with dose adjustments in HD patients. Four types of oral antidiabetic drugs can be administered for combination oral therapy with DPP-4 inhibitors, including sulfonylureas, meglitinide, thiazolidinediones, and alpha-glucosidase inhibitor. Nine studies examined the antidiabetic effects in HD patients. Treatments decreased hemoglobin A1c and glycated albumin levels by 0.3% to 1.3% and 1.7% to 4.9%, respectively. The efficacy of DPP-4 inhibitor treatment is high among HD patients, and no patients exhibited significant severe adverse effects such as hypoglycemia and liver dysfunction. DPP-4 inhibitors are key drugs in new treatment strategies for HD patients with diabetes and with limited choices for diabetes treatment. PMID:26131325

Antidiabetic activity of the mangrove species Ceriops decandra in alloxan-induced diabetic rats.

PubMed

Nabeel, Mannalamkunnath Alikunhi; Kathiresan, Kandasamy; Manivannan, Subramanian

2010-06-01

Diabetes is a series of disorders characterized by increased fasting and postprandial glucose concentration and insulin deficiency and/or decreased insulin action. Although there are a number of commercially available drugs for the treatment of diabetes, their long-term use may cause unwanted side effects. Consequently, many studies are underway to find natural remedies that can effectively reduce the intensity of diabetes. The aim of the present study was to evaluate the antidiabetic activity of the mangrove species Ceriops decandra. The effects of daily oral administration of an ethanolic extract from the leaves of C. decandra (30, 60, 120 mg/kg) for 30 days on blood glucose, hemoglobin (Hb), HbA1c, liver glycogen and some carbohydrate metabolic enzymes were evaluated in normal and alloxan-induced diabetic rats. The effects of these extracts were compared with the effect of 30-days treatment with 0.1 mg/kg, p.o., glibenclamide, a commercially available drug commonly used in the treatment of diabetes. Oral administration of 120 mg/kg extract modulated all the parameters evaluated to levels seen in control rats. The effects of 120 mg/kg extract were comparable to those of glibenclamide. The extract of the mangrove plant C. decandra exhibited promising antidiabetic activity and could be considered for further evaluation in clinical studies and drug development. © 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

Suicide attempt by an overdose of sitagliptin, an oral hypoglycemic agent: a case report and a review of the literature.

PubMed

Furukawa, Shinya; Kumagi, Teru; Miyake, Teruki; Ueda, Teruhisa; Niiya, Tetsuji; Nishino, Keiichiro; Murakami, Shigeto; Murakami, Masato; Matsuura, Bunzo; Onji, Morikazu

2012-01-01

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a newer class of oral hypoglycemic agents for the management of diabetes that elevate the plasma concentration of active glucagon-like peptide-1 via inhibition of DPP-4. They effectively lower not only glycosylated hemoglobin levels, but also fasting and postprandial plasma glucose levels. Patients with diabetes occasionally consume an overdose of oral hypoglycemic agents in suicide attempts: the prevalence of depression is high in patients with diabetes, and depression is a strong risk factor for suicide. We encountered an 86-year-old woman with type 2 diabetes and depression, who was transferred to the emergency room 4h after ingestion of 1,700 mg of the DPP-4 inhibitor sitagliptin (1,700 mg is 17 times greater than the approved maximum dose). Upon arrival, she was fully conscious, plasma glucose was 124 mg/dL, and serum immunoreactive insulin level was 5.81 µU/mL. Thereafter, the plasma concentration of sitagliptin rose to 3,793 nM, which is 4.5 times higher than the value found under regular treatment with the maximum dose. The patient did not suffer from hypoglycemia, suggesting that a single oral overdose of sitagliptin is unlikely to cause hypoglycemia. A literature review of oral anti-diabetic agents revealed that overdose of biguanides is occasionally fatal when immediate intensive care is not provided. In summary, sitagliptin is a good treatment option for diabetic elderly patients or patients with psychiatric disorders who are suicidal and do not require insulin.

Potential therapeutic applications of multifunctional host-defense peptides from frog skin as anti-cancer, anti-viral, immunomodulatory, and anti-diabetic agents.

PubMed

Conlon, J Michael; Mechkarska, Milena; Lukic, Miodrag L; Flatt, Peter R

2014-07-01

Frog skin constitutes a rich source of peptides with a wide range of biological properties. These include host-defense peptides with cytotoxic activities against bacteria, fungi, protozoa, viruses, and mammalian cells. Several hundred such peptides from diverse species have been described. Although attention has been focused mainly on antimicrobial activity, the therapeutic potential of frog skin peptides as anti-infective agents remains to be realized and no compound based upon their structures has yet been adopted in clinical practice. Consequently, alternative applications are being explored. Certain naturally occurring frog skin peptides, and analogs with improved therapeutic properties, show selective cytotoxicity against tumor cells and viruses and so have potential for development into anti-cancer and anti-viral agents. Some peptides display complex cytokine-mediated immunomodulatory properties. Effects on the production of both pro-inflammatory and anti-inflammatory cytokines by peritoneal macrophages and peripheral blood mononuclear cells have been observed so that clinical applications as anti-inflammatory, immunosuppressive, and immunostimulatory agents are possible. Several frog skin peptides, first identified on the basis of antimicrobial activity, have been shown to stimulate insulin release both in vitro and in vivo and so show potential as incretin-based therapies for treatment of patients with Type 2 diabetes mellitus. This review assesses the therapeutic possibilities of peptides from frogs belonging to the Ascaphidae, Alytidae, Pipidae, Dicroglossidae, Leptodactylidae, Hylidae, and Ranidae families that complement their potential role as anti-infectives for use against multidrug-resistant microorganisms. Copyright © 2014 Elsevier Inc. All rights reserved.

N-hydroxycinnamide derivatives of osthole ameliorate hyperglycemia through activation of AMPK and p38 MAPK.

PubMed

Lee, Wei-Hwa; Wu, Hsueh-Hsia; Huang, Wei-Jan; Li, Yi-Ning; Lin, Ren-Jye; Lin, Shyr-Yi; Liang, Yu-Chih

2015-03-11

Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes. Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes.

Antidiabetic phytoconstituents and their mode of action on metabolic pathways

PubMed Central

Bharti, Sudhanshu Kumar; Krishnan, Supriya; Kumar, Ashwini

2018-01-01

Diabetes Mellitus, characterized by persistent hyperglycaemia, is a heterogeneous group of disorders of multiple aetiologies. It affects the human body at multiple organ levels thus making it difficult to follow a particular line of the treatment protocol and requires a multimodal approach. The increasing medical burden on patients with diabetes-related complications results in an enormous economic burden, which could severely impair global economic growth in the near future. This shows that today’s healthcare system has conventionally been poorly equipped towards confronting the mounting impact of diabetes on a global scale and demands an urgent need for newer and better options. The overall challenge of this field of diabetes treatment is to identify the individualized factors that can lead to improved glycaemic control. Plants are traditionally used worldwide as remedies for diabetes healing. They synthesize a diverse array of biologically active compounds having antidiabetic properties. This review is an endeavour to document the present armamentarium of antidiabetic herbal drug discovery and developments, highlighting mechanism-based antidiabetic properties of over 300 different phytoconstituents of various chemical categories from about 100 different plants modulating different metabolic pathways such as glycolysis, Krebs cycle, gluconeogenesis, glycogen synthesis and degradation, cholesterol synthesis, carbohydrate metabolism as well as peroxisome proliferator activated receptor activation, dipeptidyl peptidase inhibition and free radical scavenging action. The aim is to provide a rich reservoir of pharmacologically established antidiabetic phytoconstituents with specific references to the novel, cost-effective interventions, which might be of relevance to other low-income and middle-income countries of the world. PMID:29492244

An adenovirus-derived protein: A novel candidate for anti-diabetic drug development

PubMed Central

Hegde, Vijay; Na, Ha-Na; Dubuisson, Olga; Burke, Susan J.; Collier, J. Jason; Burk, David; Mendoza, Tamra; Dhurandhar, Nikhil V.

2016-01-01

Aims Exposure to human adenovirus Ad36 is causatively and correlatively linked with better glycemic control in animals and humans, respectively. Although the anti-hyperglycemic property of Ad36 may offer some therapeutic potential, it is impractical to use an infectious agent for therapeutic benefit. Cell- based studies identified that Ad36 enhances cellular glucose disposal via its E4orf1 protein. Ability to improve glycemic control in vivo is a critical prerequisite for further investigating the therapeutic potential of E4orf1. Therefore, the aim of this study was to determine the ability of E4orf1 to improve glycemic control independent of insulin despite high fat diet. Materials & Methods 8–9wk old male C57BL/6J mice fed a high-fat diet (60% kcal) were injected with a retrovirus plasmid expressing E4orf1, or a null vector (Control). Glycemic control was determined by glucose and insulin tolerance test. Islet cell size, amount of insulin and glucagon were determined in formalin-fixed pancreas. Rat insulinoma cell line (832/13) was infected with E4orf1 or control to determine changes in glucose stimulated insulin secretion. Protein from flash frozen adipose tissue depots, liver and muscle was used to determine molecular signaling by western blotting. Results In multiple experiments, retrovirus-mediated E4orf1 expression in C57BL/6J mice significantly and reproducibly improved glucose excursion following a glucose load despite a high fat diet (60% energy). Importantly, E4orf1 improved glucose clearance without increasing insulin sensitivity, production or secretion, underscoring its insulin-independent effect. E4orf1 modulated molecular signaling in mice tissue, which included greater protein abundance of adiponectin, p-AKT and Glucose transporter Glu4. Conclusions This study provides the proof of concept for translational development of E4orf1 as a potential anti-diabetic agent. High fat intake and impaired insulin signaling are often associated with obesity, diabetes and insulin resistance. Hence, the ability of E4orf1 to improve glycemic control despite high fat diet and independent of insulin, is particularly attractive. PMID:26700141

Evaluation of α-Glucosidase Inhibitory Effect of 50% Ethanolic Standardized Extract of Orthosiphon stamineus Benth in Normal and Streptozotocin-Induced Diabetic Rats

PubMed Central

Mohamed, Elsnoussi Ali; Ang, Lee Fung; Asmawi, Mohd. Zaini

2015-01-01

In the present study, a 50% ethanolic extract of Orthosiphon stamineus was tested for its α-glucosidase inhibitory activity. In vivo assays of the extract (containing 1.02%, 3.76%, and 3.03% of 3′hydroxy-5,6,7,4′-tetramethoxyflavone, sinensetin, and eupatorin, resp.) showed that it possessed an inhibitory activity against α-glucosidase in normal rats loaded with starch and sucrose. The results showed that 1000 mg/kg of the 50% ethanolic extract of O. stamineus significantly (P < 0.05) decreased the plasma glucose levels of the experimental animals in a manner resembling the effect of acarbose. In streptozotocin-induced diabetic rats, only the group treated with 1000 mg/kg of the extract showed significantly (P < 0.05) lower plasma glucose levels after starch loading. Hence, α-glucosidase inhibition might be one of the mechanisms by which O. stamineus extract exerts its antidiabetic effect. Furthermore, our findings indicated that the 50% ethanolic extract of O. stamineus can be considered as a potential agent for the management of diabetes mellitus. PMID:26649063

Evaluation of α-Glucosidase Inhibitory Effect of 50% Ethanolic Standardized Extract of Orthosiphon stamineus Benth in Normal and Streptozotocin-Induced Diabetic Rats.

PubMed

Mohamed, Elsnoussi Ali; Ahmad, Mariam; Ang, Lee Fung; Asmawi, Mohd Zaini; Yam, Mun Fei

2015-01-01

In the present study, a 50% ethanolic extract of Orthosiphon stamineus was tested for its α-glucosidase inhibitory activity. In vivo assays of the extract (containing 1.02%, 3.76%, and 3.03% of 3'hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin, resp.) showed that it possessed an inhibitory activity against α-glucosidase in normal rats loaded with starch and sucrose. The results showed that 1000 mg/kg of the 50% ethanolic extract of O. stamineus significantly (P < 0.05) decreased the plasma glucose levels of the experimental animals in a manner resembling the effect of acarbose. In streptozotocin-induced diabetic rats, only the group treated with 1000 mg/kg of the extract showed significantly (P < 0.05) lower plasma glucose levels after starch loading. Hence, α-glucosidase inhibition might be one of the mechanisms by which O. stamineus extract exerts its antidiabetic effect. Furthermore, our findings indicated that the 50% ethanolic extract of O. stamineus can be considered as a potential agent for the management of diabetes mellitus.

Antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Linn.) in streptozotocin-induced diabetic rats.

PubMed

Petchi, Ramesh R; Parasuraman, S; Vijaya, C

2013-09-01

To study the antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Asteraceae) in streptozotocin-induced diabetic rats. The whole plant of T. procumbens was collected in different regions of Madurai districts, Tamil Nadu. The air dried whole plant of T. procumbens was extracted with ethanol (95%) in a Soxhlet apparatus for 72 h. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/jk, i.p.) and nicotinamide (120 mg/kg, i.p) injection. The dry mass of the extract was used for preliminary phytochemical and pharmacological analysis. Diabetic rats were treated with glibenclamide (0.25 mg/kg, p.o.) or T. procumbens extract (250 and 500 mg/k, p.o.) for 21 consecutive days. The blood samples were collected at regular intervals to access hypoglycemic effect of an ethanolic extract of the whole plant of T. procumbens. At the end of the experiment, serum lipid profile and liver enzymes levels were analyzed for all the experimental animals and compared with diabetic control. The preliminary phytochemical analysis of an ethanolic extract of the whole plant of T. procumbens indicated the presence of alkaloids, tannins, flavonoids, saponins, and phenolic compounds. The ethanolic extract of the whole plant of T. procumbens at 250 and 500 mg/kg has significant antidiabetic and antihyperlipidemic activities. The diabetic control animals exhibited a significant decrease in body weight compared with control animals. T. procumbens inhibited streptozotocin-induced weight loss and significantly alter the lipid levels. The ethanolic extract of the whole plant of T. procumbens showed significant antidiabetic and antihyperlipidemic activities against streptozotocin-induced diabetes in rats.

Antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Linn.) in streptozotocin-induced diabetic rats

PubMed Central

Petchi, Ramesh R.; Parasuraman, S.; Vijaya, C.

2013-01-01

Objective: To study the antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Asteraceae) in streptozotocin-induced diabetic rats. Materials and Methods: The whole plant of T. procumbens was collected in different regions of Madurai districts, Tamil Nadu. The air dried whole plant of T. procumbens was extracted with ethanol (95%) in a Soxhlet apparatus for 72 h. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/jk, i.p.) and nicotinamide (120 mg/kg, i.p) injection. The dry mass of the extract was used for preliminary phytochemical and pharmacological analysis. Diabetic rats were treated with glibenclamide (0.25 mg/kg, p.o.) or T. procumbens extract (250 and 500 mg/k, p.o.) for 21 consecutive days. The blood samples were collected at regular intervals to access hypoglycemic effect of an ethanolic extract of the whole plant of T. procumbens. At the end of the experiment, serum lipid profile and liver enzymes levels were analyzed for all the experimental animals and compared with diabetic control. Results: The preliminary phytochemical analysis of an ethanolic extract of the whole plant of T. procumbens indicated the presence of alkaloids, tannins, flavonoids, saponins, and phenolic compounds. The ethanolic extract of the whole plant of T. procumbens at 250 and 500 mg/kg has significant antidiabetic and antihyperlipidemic activities. The diabetic control animals exhibited a significant decrease in body weight compared with control animals. T. procumbens inhibited streptozotocin-induced weight loss and significantly alter the lipid levels. Conclusion: The ethanolic extract of the whole plant of T. procumbens showed significant antidiabetic and antihyperlipidemic activities against streptozotocin-induced diabetes in rats. PMID:24808679

Antioxidant and antidiabetic properties of condensed tannins in acetonic extract of selected raw and processed indigenous food ingredients from Kenya.

PubMed

Kunyanga, Catherine Nkirote; Imungi, Jasper Kathenya; Okoth, Michael; Momanyi, Clare; Biesalski, Han Konrad; Vadivel, Vellingiri

2011-05-01

Recently, tannins have received considerable attention as health-promoting component in various plant foods and several studies have reported on its nutraceutical properties. However, no study has established the role of condensed tannins in indigenous foods of Kenya. Therefore, this study was designed to evaluate the antioxidant activity (DPPH and FRAP) and antidiabetic effects (α-amylase and α-glucosidase inhibition activities) of condensed tannins in some selected raw and traditionally processed indigenous cereals, legumes, oil seeds, and vegetables. The condensed tannin content of the grains and vegetables ranged between 2.55 and 4.35 g/100 g DM and 1.53 and 5.73 g/100 g DM, respectively. The scavenging effect of acetonic extract on DPPH radical ranged from 77% to 90% while the reducing power was found to be 31 to 574 mmol Fe(II)/g DM in all the investigated food ingredients. The condensed tannin extracts of the analyzed samples showed promising antidiabetic effects with potential α-amylase and α-glucosidase inhibition activities of 23% to 44% and 58% to 88%, respectively. Condensed tannins extracted from the amaranth grain, finger millet, field bean, sunflower seeds, drumstick, and amaranth leaves exerted significantly higher antioxidant and antidiabetic activities than other food ingredients. Among the traditional processing methods, roasting of grains and cooking of vegetables were found to be more suitable mild treatments for preserving the tannin compound and its functional properties as opposed to soaking + cooking and blanching treatments. The identified elite sources of optimally processed indigenous food ingredients with promising results could be used as health-promoting ingredients through formulation of therapeutic diets. © 2011 Institute of Food Technologists®

Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root’s hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice

PubMed Central

Ahangarpour, Akram; Heidari, Hamid; Oroojan, Ali Akbar; Mirzavandi, Farhang; Nasr Esfehani, Khalil; Dehghan Mohammadi, Zeinab

2017-01-01

Objective: Arctium lappa (burdock), (A. lappa) root has hypoglycemic and antioxidative effects, and has been used for treatment of diabetes in tradition medicine. This study was conducted to evaluate the antidiabetic and hypolipidemic properties of A. lappa root extract on nicotinamide-streptozotocin (NA-STZ)-induced type2 diabetes in mice. Materials and Methods: In this investigation, 70 adult male NMRI mice (30-35g) randomly divided into 7 groups (n=10) as follow: 1-control, 2-type 2 diabetic mice, 3-diabetic mice that received glibenclamide (0.25 mg/kg) as an anti-diabetic drug, 4, 5, 6 and 7- diabetic and normal animals that were pre-treated with 200 and 300 mg/kg A. lappa root extract, respectively, for 28 days. Diabetes has been induced by intraperitoneal injection of NA and STZ. Finally, the blood sample was taken and insulin, glucose, SGOT, SGPT, alkaline phosphatase, leptin and lipid levels was evaluated. Results: Induction of diabetes decreased the level of insulin, leptin and high density lipoprotein (HDL) and increased the level of other lipids, glucose, and hepatic enzymes significantly (p<0.05). Administration of both doses of the extract significantly decreased the level of triglyceride, very low density lipoprotein, glucose and alkaline phosphatase in diabetic mice (p<0.05). Insulin levels increased in animals treated with 200 mg/kg (p<0.05) and HDL and leptin levels increased in animals treated with 300 mg/kg of the extract (p<0.01). Conclusion: The results showed that A. lappa root extract, at specific doses, has an anti-diabetic effect through its hypolipidemic and insulinotropic properties. Hence, this plant extract may be beneficial in the treatment of diabetes. PMID:28348972

Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root's hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice.

PubMed

Ahangarpour, Akram; Heidari, Hamid; Oroojan, Ali Akbar; Mirzavandi, Farhang; Nasr Esfehani, Khalil; Dehghan Mohammadi, Zeinab

2017-01-01

Arctium lappa (burdock), (A. lappa) root has hypoglycemic and antioxidative effects, and has been used for treatment of diabetes in tradition medicine. This study was conducted to evaluate the antidiabetic and hypolipidemic properties of A. lappa root extract on nicotinamide-streptozotocin (NA-STZ)-induced type2 diabetes in mice. In this investigation, 70 adult male NMRI mice (30-35g) randomly divided into 7 groups (n=10) as follow: 1-control, 2-type 2 diabetic mice, 3-diabetic mice that received glibenclamide (0.25 mg/kg) as an anti-diabetic drug, 4, 5, 6 and 7- diabetic and normal animals that were pre-treated with 200 and 300 mg/kg A. lappa root extract, respectively, for 28 days. Diabetes has been induced by intraperitoneal injection of NA and STZ. Finally, the blood sample was taken and insulin, glucose, SGOT, SGPT, alkaline phosphatase, leptin and lipid levels was evaluated. Induction of diabetes decreased the level of insulin, leptin and high density lipoprotein (HDL) and increased the level of other lipids, glucose, and hepatic enzymes significantly (p<0.05). Administration of both doses of the extract significantly decreased the level of triglyceride, very low density lipoprotein, glucose and alkaline phosphatase in diabetic mice (p<0.05). Insulin levels increased in animals treated with 200 mg/kg (p<0.05) and HDL and leptin levels increased in animals treated with 300 mg/kg of the extract (p<0.01). The results showed that A. lappa root extract, at specific doses, has an anti-diabetic effect through its hypolipidemic and insulinotropic properties. Hence, this plant extract may be beneficial in the treatment of diabetes.

Cost effectiveness of dipeptidyl peptidase-4 inhibitors for type 2 diabetes.

PubMed

Geng, Jinsong; Yu, Hao; Mao, Yiwei; Zhang, Peng; Chen, Yingyao

2015-06-01

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs used for treating type 2 diabetes mellitus. While many studies have reported on the cost-effectiveness of DPP-4 inhibitors for treating type 2 diabetes, a systematic review of economic evaluations of DPP-4 inhibitors is currently lacking. The aim of this systematic review was to assess the cost effectiveness of DPP-4 inhibitors for patients with type 2 diabetes. MEDLINE, EMBASE, National Health Service Economic Evaluation Database (NHS EED), Web of Science, EconLit databases, and the Cochrane Library were searched in November 2013. Studies assessing the cost effectiveness of DPP-4 inhibitors for type 2 diabetes were eligible for analysis. DPP-4 inhibitor monotherapy or combinations with other antidiabetic agents were included in the review. The DPP-4 inhibitors were all marketed drugs. Two reviewers independently reviewed titles, abstracts, and articles sequentially to select studies for data abstraction based on the inclusion and exclusion criteria. Disagreements were resolved by consensus. The quality of included studies was assessed according to the 24-item checklist of the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. The costs reported by the included studies were converted to US dollars via purchasing power parities (PPP) in the year 2013 using the CCEMG-EPPI-Center Cost Converter. A total of 11 published studies were selected for inclusion; all were cost-utility analyses. Nine studies were conducted from a payer perspective and one used a societal perspective; however, the perspective of the other study was unclear. Four studies were of good quality, six were of moderate quality, and one was of low quality. Of the seven studies comparing DPP-4 inhibitors plus metformin with sulfonylureas plus metformin, six concluded that DPP-4 inhibitors were cost effective in patients with type 2 diabetes who were no longer adequately controlled by metformin monotherapy. Five studies compared DPP-4 inhibitors with thiazolidinediones, and whether DPP-4 inhibitors were cost effective was uncertain. Only two economic evaluations provided data to compare DPP-4 inhibitors versus insulin, and the results favored the use of DPP-4 inhibitors as second-line therapy. Synthesis of the data was impossible because of heterogeneity in the methodology and data sources of the economic evaluations, and the inclusion criteria excluded conference abstracts. It was difficult to find reliable weightings for each of the items of the CHEERS checklist, and the ratings were dichotomous. This study provides the first systematic evaluation of DPP-4 inhibitors for patients with type 2 diabetes. It found that, in patients with type 2 diabetes who do not achieve glycemic targets with antidiabetic monotherapy, DPP-4 inhibitors as add-on treatment may represent a cost-effective option compared with sulfonylureas and insulin. However, high-quality cost-effectiveness analyses that utilize long-term follow-up data and have no conflicts of interest are still needed.

Drug development from the bench to the pharmacy: with special reference to dipeptidyl peptidase-4 inhibitor development.

PubMed

Carr, R D

2016-06-01

The dipeptidyl peptidase-4 (DPP-4) inhibitor concept is an example of prospective drug design and development based upon a distinct endocrine hypothesis. The design of enzyme inhibitors is a pragmatic approach to drug design; being compatible with the identification and optimization of small molecules that have properties commensurate with oral administration, as well as acceptable drug metabolism, distribution and elimination characteristics. Glucagon-like peptide 1 (GLP-1), a hormone with a spectrum of favourable metabolic actions, including glucose-dependent stimulation of insulin and inhibition of glucagon secretion, provided the endocrine basis from which the idea of using DPP-4 inhibitors as anti-diabetic agents was developed. The origin of the DPP-4 inhibitor concept was inspired by the angiotensin-converting enzyme inhibitor approach, which succeeded in establishing a class of extensively used therapeutic agents for the treatment of cardiovascular disorders. © 2016 Diabetes UK.

Marine Natural Product Bis-indole Alkaloid Caulerpin: Chemistry and Biology.

PubMed

Lunagariya, Jignesh; Bhadja, Poonam; Zhong, Shenghui; Vekariya, Rohit; Xu, Shihai

2017-09-27

Marine bis-indole alkaloids comprise a large and increasingly growing class of secondary metabolites, and continue to deliver a great variety of structural templates. The alkaloids derived from marine resources play a crucial role in medicinal chemistry and as chemical agents. In particular, bis-indole alkaloid caulerpin isolated from marine green algae Caulerpa and a red algae Chondria armata at various places around the world, and tested against several therapeutic areas such as anti-diabetic, antinociceptive, anti-inflammatory, anti-tumor, anti-larvicidal, anti-herpes, anti-tubercular, anti-microbial and immunostimulating activity as well as means of other chemical agents. Herein, we summarized discovery of caulerpin, and its potential medicinal and chemical applications in chronological order with various aspects. Additionally, synthesis of caulerpin, its functional analogues, and structural isomer have also been reviewed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti-Obesity, Anti-Diabetic and Lipid Modulating Agents

PubMed Central

Hansen, Gitte; Fabricius, Katrine; Hansen, Henrik B.; Jelsing, Jacob; Vrang, Niels

2015-01-01

Aim Unlike rats and mice, hamsters develop hypercholesterolemia, and hypertriglyceridemia when fed a cholesterol-rich diet. Because hyperlipidemia is a hallmark of human obesity, we aimed to develop and characterize a novel diet-induced obesity (DIO) and hypercholesterolemia Golden Syrian hamster model. Methods and Results Hamsters fed a highly palatable fat- and sugar-rich diet (HPFS) for 12 weeks showed significant body weight gain, body fat accumulation and impaired glucose tolerance. Cholesterol supplementation to the diet evoked additional hypercholesterolemia. Chronic treatment with the GLP-1 analogue, liraglutide (0.2 mg/kg, SC, BID, 27 days), normalized body weight and glucose tolerance, and lowered blood lipids in the DIO-hamster. The dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin (3.0 mg/kg, PO, QD) also improved glucose tolerance. Treatment with peptide YY3-36 (PYY3-36, 1.0 mg/kg/day) or neuromedin U (NMU, 1.5 mg/kg/day), continuously infused via a subcutaneous osmotic minipump for 14 days, reduced body weight and energy intake and changed food preference from HPFS diet towards chow. Co-treatment with liraglutide and PYY3-36 evoked a pronounced synergistic decrease in body weight and food intake with no lower plateau established. Treatment with the cholesterol uptake inhibitor ezetimibe (10 mg/kg, PO, QD) for 14 days lowered plasma total cholesterol with a more marked reduction of LDL levels, as compared to HDL, indicating additional sensitivity to cholesterol modulating drugs in the hyperlipidemic DIO-hamster. In conclusion, the features of combined obesity, impaired glucose tolerance and hypercholesterolemia in the DIO-hamster make this animal model useful for preclinical evaluation of novel anti-obesity, anti-diabetic and lipid modulating agents. PMID:26266945

Drug-class-specific changes in the volume and cost of antidiabetic medications in Poland between 2012 and 2015.

PubMed

Śliwczyński, Andrzej; Brzozowska, Melania; Jacyna, Andrzej; Iltchev, Petre; Iwańczuk, Tymoteusz; Wierzba, Waldemar; Marczak, Michał; Orlewska, Katarzyna; Szymański, Piotr; Orlewska, Ewa

2017-01-01

to investigate the drug-class-specific changes in the volume and cost of antidiabetic medications in Poland in 2012-2015. This retrospective analysis was conducted based on the National Health Fund database covering an entire Polish population. The volume of antidiabetic medications is reported according to ATC/DDD methodology, costs-in current international dollars, based on purchasing power parity. During a 4-year observational period the number of patients, consumption of antidiabetic drugs and costs increased by 17%, 21% and 20%, respectively. Biguanides are the basic diabetes medication with a 39% market share. The insulin market is still dominated by human insulins, new antidiabetics (incretins, thiazolidinediones) are practically absent. Insulins had the largest share in diabetes medications expenditures (67% in 2015). The increase in antidiabetic medications costs over the analysed period of time was mainly caused by the increased use of insulin analogues. The observed tendencies correspond to the evidence-based HTA recommendations. The reimbursement status, the ratio of cost to clinical outcomes and data on the long-term safety have a deciding impact on how a drug is used.

Why Antidiabetic Vanadium Complexes are Not in the Pipeline of "Big Pharma" Drug Research? A Critical Review.

PubMed

Scior, Thomas; Guevara-Garcia, Jose Antonio; Do, Quoc-Tuan; Bernard, Philippe; Laufer, Stefan

2016-01-01

Public academic research sites, private institutions as well as small companies have made substantial contributions to the ongoing development of antidiabetic vanadium compounds. But why is this endeavor not echoed by the globally operating pharmaceutical companies, also known as "Big Pharma"? Intriguingly, today's clinical practice is in great need to improve or replace insulin treatment against Diabetes Mellitus (DM). Insulin is the mainstay therapeutically and economically. So, why do those companies develop potential antidiabetic drug candidates without vanadium (vanadium- free)? We gathered information about physicochemical and pharmacological properties of known vanadium-containing antidiabetic compounds from the specialized literature, and converted the data into explanations (arguments, the "pros and cons") about the underpinnings of antidiabetic vanadium. Some discoveries were embedded in chronological order while seminal reviews of the last decade about the Medicinal chemistry of vanadium and its history were also listed for further understanding. In particular, the concepts of so-called "noncomplexed or free" vanadium species (i.e. inorganic oxido-coordinated species) and "biogenic speciation" of antidiabetic vanadium complexes were found critical and subsequently documented in more details to answer the question.

Synergistic Anti-Cancer Effect of Phenformin and Oxamate

PubMed Central

Miskimins, W. Keith; Ahn, Hyun Joo; Kim, Ji Yeon; Ryu, Sun; Jung, Yuh-Seog; Choi, Joon Young

2014-01-01

Phenformin (phenethylbiguanide; an anti-diabetic agent) plus oxamate [lactate dehydrogenase (LDH) inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS). Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively. PMID:24465604

Synergistic anti-cancer effect of phenformin and oxamate.

PubMed

Miskimins, W Keith; Ahn, Hyun Joo; Kim, Ji Yeon; Ryu, Sun; Jung, Yuh-Seog; Choi, Joon Young

2014-01-01

Phenformin (phenethylbiguanide; an anti-diabetic agent) plus oxamate [lactate dehydrogenase (LDH) inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS). Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively.

Herbal Therapies for Type 2 Diabetes Mellitus: Chemistry, Biology, and Potential Application of Selected Plants and Compounds

PubMed Central

Chang, Cicero L. T.; Bartolome, Arlene P.; Chen, Yi-Ching; Chiu, Shao-Chih

2013-01-01

Diabetes mellitus has been recognized since antiquity. It currently affects as many as 285 million people worldwide and results in heavy personal and national economic burdens. Considerable progress has been made in orthodox antidiabetic drugs. However, new remedies are still in great demand because of the limited efficacy and undesirable side effects of current orthodox drugs. Nature is an extraordinary source of antidiabetic medicines. To date, more than 1200 flowering plants have been claimed to have antidiabetic properties. Among them, one-third have been scientifically studied and documented in around 460 publications. In this review, we select and discuss blood glucose-lowering medicinal herbs that have the ability to modulate one or more of the pathways that regulate insulin resistance, β-cell function, GLP-1 homeostasis, and glucose (re)absorption. Emphasis is placed on phytochemistry, anti-diabetic bioactivities, and likely mechanism(s). Recent progress in the understanding of the biological actions, mechanisms, and therapeutic potential of compounds and extracts of plant origin in type 2 diabetes is summarized. This review provides a source of up-to-date information for further basic and clinical research into herbal therapy for type 2 diabetes. Emerging views on therapeutic strategies for type 2 diabetes are also discussed. PMID:23662132

Evaluation and structure-activity relationship analysis of a new series of 4-imino-5H-pyrazolo[3,4-d]pyrimidin-5-amines as potential antibacterial agents

NASA Astrophysics Data System (ADS)

Beyzaei, Hamid; Aryan, Reza; Moghaddam-Manesh, Mohammadreza; Ghasemi, Behzad; Karimi, Pouya; Samareh Delarami, Hojat; Sanchooli, Mahmood

2017-09-01

The synthesis of pyrazolo[3,4-d]pyrimidine derivatives is important due to their presence in various biologically active compounds such as anticancer, antimicrobial, antiparasitic, anti-inflammatory and antidiabetic agents. In this project, a new and efficient approach for the synthesis of some novel 4-imino-5H-pyrazolo[3,4-d]pyrimidin-5-amines from reaction of 5-amino-pyrazole-4-carbonitrile with various hydrazides in ethanolic sodium ethoxide medium was reported. Antimicrobial activities of all synthesized derivatives were evaluated against eight Gram-positive and five Gram-negative pathogenic bacteria. The moderate to good inhibitory effects were observed based on inhibition zone diameter (IZD), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. In order to determine the reasonable relationship between antibacterial activities and physiochemical properties of the derivatives, computational studies were carried out in terms of geometry optimization, short-range van der Waals forces, dipole moments, atomic charges and frontier orbital energies. It was found that both short-range forces and covalent bonds are important in the observed inhibitory effects of the molecules. The results suggested that pyrazolo[3,4-d]pyrimidine derivatives prefer a soft nucleophilic attack on bio-macromolecular targets. Furthermore, our models proposed that the antibacterial activities of these derivatives can be improved by substituting large electron donating groups on the 6-phenyl rings.

Paroxetine decreased plasma exposure of glyburide partly via inhibiting intestinal absorption in rats.

PubMed

Jiang, Shuwen; Zhao, Weiman; Chen, Yang; Zhong, Zeyu; Zhang, Mian; Li, Feng; Xu, Ping; Zhao, Kaijing; Li, Ying; Liu, Li; Liu, Xiaodong

2015-06-01

Accumulating evidences have shown that diabetes is often accompanied with depression, thus it is possible that oral antidiabetic agent glyburide and antidepressive agent paroxetine are co-administered in diabetic patients. The aim of this study was to assess interactions between glyburide and paroxetine in rats. Effect of paroxetine on pharmacokinetics of orally administered glyburide was investigated. Effect of naringin (NAR), an inhibitor of rat intestinal organic anion transporting polypeptides 1a5 (Oatp1a5), on pharmacokinetics of glyburide was also studied. The results showed that co-administration of paroxetine markedly reduced plasma exposure and prolonged Tmax of glyburide, accompanied by significant increase in fecal excretion of glyburide. Co-administration of naringin also significantly decreased plasma exposure of glyburide. Data from intestinal perfusion experiments showed that both paroxetine and naringin significantly inhibited intestinal absorption of glyburide. Caco-2 cells were used to investigate whether paroxetine and naringin affected intestinal transport of glyburide and fexofenadine (a substrate of Oatp1a5). The results showed that both paroxetine and naringin greatly inhibited absorption of glyburide and fexofenadine. All results gave a conclusion that co-administration of paroxetine decreased plasma exposure of glyburide in rats via inhibiting intestinal absorption of glyburide, which may partly be attributed to the inhibition of intestinal Oatp1a5 activity. Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Hypoglycemic and Antidiabetic Effect of Pleurotus sajor-caju Aqueous Extract in Normal and Streptozotocin-Induced Diabetic Rats

PubMed Central

Ng, Sze Han; Mohd Zain, Mohd Shazwan; Zakaria, Fatariah; Wan Ishak, Wan Rosli; Wan Ahmad, Wan Amir Nizam

2015-01-01

Introduction. Pleurotus sajor-caju (PSC) is an edible oyster mushroom featuring high nutritional values and pharmacological properties. Objective. To investigate the hypoglycemic and antidiabetic effects of single and repeated oral administration of PSC aqueous extract in normal and diabetic rats. Materials and Methods. A single dose of 500, 750, or 1000 mg/kg of the PSC extract was given to experimental rats to determine the effects on blood glucose (BG) and oral glucose tolerance test (OGTT). The effective dose (750 mg/kg) of PSC extract was repeatedly administrated daily for 21 days in diabetic rats to examine its antidiabetic effects in terms of BG control, body weight, urine sugar, HbA1c, and several serum profiles. Results. The dose of 750 mg/kg showed the most significant BG reduction (23.5%) in normal rats 6 hours after administration in BG study (p < 0.05). In OGTT study, the same dose produced a maximum BG fall of 41.3% in normal rats and 36.5% in diabetic rats 3 hours after glucose administration. In 21-day study, treated diabetic rats showed significant improvement in terms of fasting BG, body weight, and urine sugar as compared to control diabetic rats. Conclusion. The study evidenced scientifically the beneficial use of PSC as an alternative medicine in diabetes management. PMID:26682215

Effects of phentermine and phenformin on biomarkers of aging in rats.

PubMed

Anisimov, Vladimir N; Ukraintseva, Svetlana V; Anikin, Ivan V; Popovich, Irina G; Zabezhinski, Mark A; Bertsein, Lev M; Arutjunyan, Alexander V; Ingram, Donald K; Lane, Mark A; Roth, George S

2005-01-01

Caloric restriction (CR) is the only treatment known to substantially prolong both average and maximal life span in experimental animals. Interventions that mimic certain effects of CR could be potential anti-aging treatments in humans. Drugs which reduce appetite (anorexiants) represent one class of candidate treatments. Agents that reduce the glucose utilization by the organism could also represent another class of candidate CR mimetics. In our study, we addressed the following questions: (1) Does treatment with an anorexiant reduce caloric intake and body weight of experimental animals comparable to that caused by CR? (2) Does treatment with an antidiabetic agent influence caloric intake and body weight? (3) Does treatment with any of these drugs affect metabolic parameters of an organism in the way similar to that observed with CR? One hundred and twenty 6-month-old female Wistar-derived LIO rats were randomly subdivided into four groups and exposed to: (1) ad libitum feeding with placebo (controls); (2) the antidiabetic drug phenformin (2 mg/kg); (3) the anorectic drug phentermine (1 mg/kg), and (4) the same amount of food as the group with the least food intake during the previous week (pair-fed controls). Food and water intake, body weight, and rectal temperature were measured weekly during 16 weeks. At the end of the 16th week of the experiment, serum levels of glucose, total beta-lipoprotein and pre-beta-lipoprotein fractions, cholesterol, triglycerides, insulin, total triiodothyronine, and free thyroxine were estimated. The contents of diene conjugates and Schiff's bases, total antioxidant activity, the activities of Cu/Zn superoxide dismutase, glutathione S-transferase, and glutathione peroxidase, and the generation of reactive oxygen species (ROS) were studied in brain and liver homogenates and in the serum. The controls exposed to pair feeding had a significantly reduced food consumption (about 20%) as compared with the ad libitum fed controls and thus exhibited a moderate CR. Treatment with phentermine reduced the caloric intake by about 12% as compared with the ad libitum fed controls. Body weight and water intake in this group were only slightly decreased (by about 2 and 5%, respectively) as compared with the controls. The mean rectal temperature in the phentermine group (38 degrees C) was significantly higher than in the ad libitum fed (37.8 degrees C) and pair-fed (37.6 degrees C) controls. Treatment with phentermine also resulted in significantly reduced ROS levels in all tissues studied, while the highest ROS production was found in ad libitum (blood serum) and pair-fed (brain) controls. Treatment with phenformin did not significantly influence food and water consumption, body weight, and temperature when compared with the ad libitum fed controls. Rats treated with this antidiabetic drug showed intermediate values of ROS generation. Differences among the groups in total antioxidant activity were not obvious. Treatment with phentermine reduces caloric intake slightly less than is commonly observed in CR studies. CR due to forcibly reduced feeding and CR due to substance-suppressed appetite appear to act through different metabolic mechanisms and thus may affect aging and longevity in different ways. Copyright (c) 2005 S. Karger AG, Basel

A review of the new GLP-1 receptor agonist/basal insulin fixed-ratio combination products.

PubMed

Nuffer, Wesley; Guesnier, Ashley; Trujillo, Jennifer M

2018-03-01

There have been several new treatment approaches established for the management of hyperglycemia in type 2 diabetes (T2D), with treatment guidelines listing both glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and basal insulin therapies as considerations for patients who have failed to control their blood glucose with oral antidiabetic agents. New studies have highlighted the importance of initiating combination therapy earlier in the T2D disease process to avoid clinical inertia and prevent the long-term complications arising from uncontrolled diabetes. Until recently, both GLP-1 RAs and basal insulin therapies were only available as single agents, but there are now two combination pen devices that deliver both a GLP-1 RA and basal insulin simultaneously. This article reviews the current clinical evidence evaluating the use of these combination GLP-1 RA/basal insulin preparations to treat T2D, presents both potential benefits as well as possible downsides with the use of these agents, and discusses the current place in therapy these products represent in the management of T2D.

Distress and Its Effect on Adherence to Antidiabetic Medications Among Type 2 Diabetes Patients in Coastal South India

PubMed Central

Kumar, Nithin; Unnikrishnan, Bhaskaran; Thapar, Rekha; Mithra, Prasanna; Kulkarni, Vaman; Holla, Ramesh; Bhagawan, Darshan; Kumar, Avinash; Aithal, Shodhan

2017-01-01

Background: Distress can bring about an unfavorable attitude among the patients toward tackling their disease which can affect adherence to medications. The purpose of this study was to assess the effect of distress on adherence to medication among patients with diabetes. Methodology: In this cross-sectional study, 124 type 2 diabetes patients above 18 years, attending the hospitals affiliated to Kasturba Medical College, Mangalore, selected using nonprobability sampling were interviewed to assess the presence of diabetes-related distress (DRD) and their level of adherence to medications. Distress was assessed using diabetes distress scale. Morisky Adherence Questionnaire was used to assess the level of adherence. Approval was obtained from the Institutional Ethics Committee. Multivariate logistic regression was conducted to assess the influence of domains of distress on adherence to antidiabetic medication and P < 0.05 was considered statistically significant. Results: In our study, 41.9% (n = 52) of the participants had high diabetes distress. Exactly 43.5% (n = 54) of the participants had low adherence to antidiabetic medications. On univariate analysis, participants with low regimen distress, low physician distress, and low interpersonal distress were found to have good adherence to antidiabetic medication. However, on multivariate analysis, only low regimen distress was found to be significantly associated with good adherence to medication among the study participants. Conclusion: DRD is a problem in our study participants which affects the adherence to medications. Identifying distress at an early stage can help doctors formulate and implement remedial measures, thereby improving adherence to medications. PMID:28781491

News from Tartary: an ethnopharmacological approach to drug and therapeutic discovery

PubMed Central

Hamza, Nawel; Berke, Benedicte; Umar, Anwar

2016-01-01

Ethnopharmacology aims to identify new therapeutic agents based on their traditional use. It begins by the identification of disease states, and of the traditional therapies for these, most commonly herbals. Herbals of interest are selected from ethnopharmacological surveys, and tested on experimental models of the diseases of interest. Once the activity of the traditional remedy is demonstrated, including dose‐dependence, if possible comparatively to reference medications, the active ingredients can be explored, if possible using bioguided extraction. Identified molecules can then be further developed as medicinal products or pharmaceutical medicines (e.g., artemisine), or the herbal product can be developed as such (e.g. St John's wort). We provide examples of various study programmes, concerning the antiplatelet and antithrombotic effects of Armagnac extracts from Southwest France; antithrombotic and antihypertensive effects of extracts of Ocimum basilicum L; antithrombotic, antihypertensive and antihyperlipidemic effects of Cydonia oblonga; Antiproliferative and antithrombotic effects of Abnorma Savda Munziq of traditional Uyghur medicine; and the antidiabetic and hepatoprotective effects of Centaurium erythraea Rafn, Artemisia herba‐alba Asso and Trigonella foenum‐graecum L., all in collaboration between University of Bordeaux, France, Xinjiang Medical University in Urumqi, China and University Mentouri in Constantine, Algeria. PMID:27297624

Repaglinide, but not nateglinide administered supraspinally and spinally exerts an anti-diabetic action in d-glucose fed and streptozotocin-treated mouse models.

PubMed

Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Suh, Hong-Won

2013-12-01

We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to 30 µg of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models.

Association Between Loyalty to Community Pharmacy and Medication Persistence and Compliance, and the Use of Guidelines-Recommended Drugs in Type 2 Diabetes

PubMed Central

Dossa, Anara Richi; Grégoire, Jean-Pierre; Lauzier, Sophie; Guénette, Line; Sirois, Caroline; Moisan, Jocelyne

2015-01-01

Abstract Pharmacists record data on all drugs claimed and may build a personal relationship with their clients. We hypothesized that loyalty to a single pharmacy could be associated with a better quality of drug use. To assess the association between pharmacy loyalty and quality of drug use among individuals treated with oral antidiabetes drugs (OADs). This is a cohort study using Quebec Health Insurance Board data. Associations were assessed using multivariable logistic regression. New OAD users, aged ≥18 years. Individuals who filled all their prescription drugs in the same pharmacy during the first year of treatment were considered loyal. During year 2 of treatment we assessed 4 quality indicators of drug use: persistence with antidiabetes treatment, compliance with antidiabetes treatment among those considered persistent, use of an angiotensin-converting enzyme inhibitor or of an angiotensin II receptor blocker (ACEi/ARB), and use of a lipid-lowering drug. Of 124,009 individuals, 59.75% were identified as loyal. Nonloyal individuals were less likely to persist with their antidiabetes treatment (adjusted odds ratio = 0.89; 95% CI: 0.86–0.91), to comply with their antidiabetes treatment (0.82; 0.79–0.84), to use an ACEi/ARB (0.85; 0.83–0.88) and to use a lipid-lowering drug (0.83; 0.80–0.85). Quality of drug use decreased as the number of different pharmacies increased (linear contrast tests <0.001). Results underscore the important role pharmacists could play in helping their clients with chronic diseases to better manage their drug treatments. Further research is needed to determine to what extent the positive effects associated with pharmacy loyalty are specifically due to pharmacists. PMID:26166087

Association Between Loyalty to Community Pharmacy and Medication Persistence and Compliance, and the Use of Guidelines-Recommended Drugs in Type 2 Diabetes: A Cohort Study.

PubMed

Dossa, Anara Richi; Grégoire, Jean-Pierre; Lauzier, Sophie; Guénette, Line; Sirois, Caroline; Moisan, Jocelyne

2015-07-01

Pharmacists record data on all drugs claimed and may build a personal relationship with their clients. We hypothesized that loyalty to a single pharmacy could be associated with a better quality of drug use.To assess the association between pharmacy loyalty and quality of drug use among individuals treated with oral antidiabetes drugs (OADs).This is a cohort study using Quebec Health Insurance Board data. Associations were assessed using multivariable logistic regression.New OAD users, aged ≥18 years.Individuals who filled all their prescription drugs in the same pharmacy during the first year of treatment were considered loyal. During year 2 of treatment we assessed 4 quality indicators of drug use: persistence with antidiabetes treatment, compliance with antidiabetes treatment among those considered persistent, use of an angiotensin-converting enzyme inhibitor or of an angiotensin II receptor blocker (ACEi/ARB), and use of a lipid-lowering drug.Of 124,009 individuals, 59.75% were identified as loyal. Nonloyal individuals were less likely to persist with their antidiabetes treatment (adjusted odds ratio = 0.89; 95% CI: 0.86-0.91), to comply with their antidiabetes treatment (0.82; 0.79-0.84), to use an ACEi/ARB (0.85; 0.83-0.88) and to use a lipid-lowering drug (0.83; 0.80-0.85). Quality of drug use decreased as the number of different pharmacies increased (linear contrast tests <0.001).Results underscore the important role pharmacists could play in helping their clients with chronic diseases to better manage their drug treatments. Further research is needed to determine to what extent the positive effects associated with pharmacy loyalty are specifically due to pharmacists.

Repaglinide, but Not Nateglinide Administered Supraspinally and Spinally Exerts an Anti-Diabetic Action in D-Glucose Fed and Streptozotocin-Treated Mouse Models

PubMed Central

Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Kim, Sung-Su; Kim, Chea-Ha; Kim, Su-Jin; Lim, Su-Min; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi

2013-01-01

We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to 30 µg of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models. PMID:24381497

The lysosome among targets of metformin: new anti-inflammatory uses for an old drug?

PubMed

Lockwood, Thomas D

2010-05-01

Rheumatoid arthritis and type-2 diabetes exhibit progressive co-morbidity. Chloroquine (CQ) reportedly improves both. CQ inhibits lysosomal function in cultured cells at supra-therapeutic concentration; however, this is doubted as target mechanism. Some anti-diabetic biguanides are metal-interactive lysosomal inhibitors; and all bind Zn(2+). i) To bioassay the potency of CQ using (3)H-leucine release from perfused myocardial tissue. ii) To determine whether metformin (MET) is CQ-mimetic, and interactive with Zn(2+). Therapeutic CQ concentration (0.1 - 0.5 microM) clearly does cause lysosomal inhibition although delayed and submaximal. MET alone (10 microM) caused sub-maximal inhibition. Supra-physiological extracellular Zn(2+) (5 - 50 microM) alone increased tissue Zn(2+) content, and inhibited lysosomal proteolysis. Physiological equivalent Zn(2+) (approximately 1 microM) had no effect. MET (

Gymnemagenin-producing endophytic fungus isolated from a medicinal plant Gymnema sylvestre R.Br.

PubMed

Parthasarathy, Ramalingam; Sathiyabama, Muthukrishnan

2014-03-01

Gymnema sylvestre is a plant containing the triterpenoid gymnemagenin, which is used in the pharmaceutical industry as an antidiabetic agent. The objective of this study was to determine whether endophytic fungi, isolated from G. sylvestre, produce gymnemagenin. We isolated an endophytic fungal strain from the leaves of G. sylvestre which produces gymnemagenin in the medium. The fungus was identified as Penicillium oxalicum based on morphological and molecular methods. The strain had a component with the same TLC Rf value and HPLC retention time as authentic gymnemagenin. The presence of gymnemagenin was further confirmed by FTIR, UV, and (1)H NMR analyses.

Why Antidiabetic Vanadium Complexes are Not in the Pipeline of “Big Pharma” Drug Research? A Critical Review

PubMed Central

Scior, Thomas; Guevara-Garcia, Jose Antonio; Do, Quoc-Tuan; Bernard, Philippe; Laufer, Stefan

2016-01-01

Public academic research sites, private institutions as well as small companies have made substantial contributions to the ongoing development of antidiabetic vanadium compounds. But why is this endeavor not echoed by the globally operating pharmaceutical companies, also known as “Big Pharma”? Intriguingly, today’s clinical practice is in great need to improve or replace insulin treatment against Diabetes Mellitus (DM). Insulin is the mainstay therapeutically and economically. So, why do those companies develop potential antidiabetic drug candidates without vanadium (vanadium-free)? We gathered information about physicochemical and pharmacological properties of known vanadium-containing antidiabetic compounds from the specialized literature, and converted the data into explanations (arguments, the “pros and cons”) about the underpinnings of antidiabetic vanadium. Some discoveries were embedded in chronological order while seminal reviews of the last decade about the Medicinal chemistry of vanadium and its history were also listed for further understanding. In particular, the concepts of so-called “noncomplexed or free” vanadium species (i.e. inorganic oxido-coordinated species) and “biogenic speciation” of antidiabetic vanadium complexes were found critical and subsequently documented in more details to answer the question. PMID:26997154

Traditional plants used for the treatment of diabetes mellitus in Sursagar constituency, Jodhpur, Rajasthan - An ethnomedicinal survey.

PubMed

Goyal, Manoj

2015-11-04

In Jodhpur, large number of people suffering with non-insulin dependent diabetes mellitus (type 2 diabetes). They are using medicinal plants along with modern medicine for the management of diabetes. The aim of this work is to document the anti-diabetic plants and determine the most relevant anti-diabetic plant species using the Disease Consensus Index. Ethnomedicinal survey was conducted for selection of anti-diabetic plant. Structured questionnaire was developed for calculation of Disease Consensus Index and administered to fifty Type 2 diabetic patients for recording their response. Twenty-one species of anti-diabetic plants were recorded, Momordica charantia (score: 0.71), Azadirachta indica (score: 0.64), Trigonella foenum-graecum (score: 0.63), Capparis decidua (score: 0.60), Withania coagulans (score: 0.54), Gymnema sylvestre (score: 0.52) and Syzygium cumini (score: 0.51) were the most significant anti-diabetic plants of the area of study, having DCI more than 0.5. Use of anti-diabetic plants is prevalent diabetic patients of the area. C. decidua, W. coagulans and G. sylvestre are recommend the further phytochemical and pharmacological investigation due to high DCI score and relatively unexplored status. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Diabetic Complications and Insight into Antidiabetic Potentialities of Ethno-medicinal Plants: A review.

PubMed

Bilal, Muhammad; Iqbal, Muhammad Sarfaraz; Shah, Syed Bilal; Rasheed, Tahir; Iqbal, Hafiz M N

2018-02-21

The naturally inspired treatment options for several disease conditions and human-health related disorders such as diabetes mellitus have gained considerable research interest. In this context, naturally occurring plants and herbs with medicinal functionalities have gained special place than ever before in the current medicinal world. The objective of this review is to extend the current knowledge in the clinical field related to the diabetic complications. A special focus has also been given to the anti-diabetic potentialities of ethnomedicinal plants. Herein, we reviewed and compiled salient information from the authentic bibliographic databases including PubMed, Scopus, Elsevier, Springer, Bentham Science and other scientific databases. The patents were searched and reviewed from http://www.freepatentsonline.com. Diabetes mellitus is a group of metabolic disorders associated with the endocrine system that resulted in hyperglycemic conditions. Metabolic disorders can cause many complications such as neuropathy, retinopathy, nephropathy, ischemic heart disease, stroke, and microangiopathy. Traditional botanical therapies have been used around the world to treat diabetes. Among several medications and different medicines, various herbs are known to cure and control diabetes; also have no side effects. History has shown that medicinal plants have long been used for traditional healing around the world to treat diabetes. More than 800 plants around the world are shown by ethnobotanical information as traditional remedies for the treatment of diabetes. Several parts of these plants have been evaluated and appreciated for hypoglycemic activity. Medicinal plants have been found to be more effective than conventional drug compounds with no/fewer side effects and relatively inexpensive. In this review paper, we have reviewed plants with anti-diabetic and related beneficial medicinal effects. This review may be helpful for researchers, diabetic patient and decision makers in the field of ethnobotanical sciences. These efforts may also provide treatment to everyone and focus on the role of traditional novel medicine plants that have anti-diabetic abilities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Customization of biliopancreatic limb length to modulate and sustain antidiabetic effect of gastric bypass surgery.

PubMed

Pal, A; Rhoads, D B; Tavakkoli, A

2018-02-01

Although Roux-en-Y Gastric Bypass (RYGB) remains the most effective treatment for obesity and type 2 diabetes (T2D), many patients fail to achieve remission, or relapse. Increasing intestinal limb lengths of RYGB may improve outcomes, but the mechanistic basis for this remains unclear. We hypothesize biliopancreatic (BP) limb length modulates the antidiabetic effect of RYGB. Rats underwent RYGB with a 20-cm (RYGB-20cm) or 40-cm (RYGB-40cm) BP limb and were compared with control animals. After 2 and 4 wk, portal and systemic blood was sampled during intestinal glucose infusion. Portosystemic gradient was used to calculate intestinal glucose utilization (G util ), absorption (G absorp ), and hormone secretion. Intestinal morphology and gene expression were assessed. At 2 wk, G absorp progressively decreased with increasing BP limb length; this pattern persisted at 4 wk. G util increased ≈70% in both RYGB-20cm and -40cm groups at 2 wk. At 4 wk, G util progressively increased with limb length. Furthermore, Roux limb weight, and expression of hexokinase and preproglucagon, exhibited a similar progressive increase. At 4 wk, glucagon-like peptide-1 and -2 levels were higher after RYGB-40cm, with associated increased secretion. We conclude that BP limb length modulates multiple antidiabetic mechanisms, analogous to the dose-response relationship of a drug. Early postoperatively, a longer BP limb reduces G absorp . Later, G util , Roux limb hypertrophy, hormone secretion, and hormone levels are increased with longer BP limb. Sustained high incretin levels may prevent weight regain and T2D relapse. These data provide the basis for customizing BP limb length according to patient characteristics and desired metabolic effect. NEW & NOTEWORTHY Biliopancreatic limb length in gastric bypass modulates multiple antidiabetic mechanisms, analogous to the dose-response relationship of a drug. With a longer biliopancreatic limb, Roux limb hypertrophy, increased glucose utilization, reduced glucose absorption, and sustained high incretin levels may prevent weight regain and diabetes relapse.

Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones

PubMed Central

Chao, Lily; Marcus-Samuels, Bernice; Mason, Mark M.; Moitra, Jaideep; Vinson, Charles; Arioglu, Elif; Gavrilova, Oksana; Reitman, Marc L.

2000-01-01

There is uncertainty about the site(s) of action of the antidiabetic thiazolidinediones (TZDs). These drugs are agonist ligands of the transcription factor PPARγ, which is abundant in adipose tissue but is normally present at very low levels in liver and muscle. We have studied the effects of TZDs in A-ZIP/F-1 mice, which lack white adipose tissue. The A-ZIP/F-1 phenotype strikingly resembles that of humans with severe lipoatrophic diabetes, including the lack of fat, marked insulin resistance and hyperglycemia, hyperlipidemia, and fatty liver. Rosiglitazone or troglitazone treatment did not reduce glucose or insulin levels, suggesting that white adipose tissue is required for the antidiabetic effects of TZDs. However, TZD treatment was effective in lowering circulating triglycerides and increasing whole body fatty acid oxidation in the A-ZIP/F-1 mice, indicating that this effect occurs via targets other than white adipose tissue. A-ZIP/F-1 mice have markedly increased liver PPARγ mRNA levels, which may be a general property of fatty livers. Rosiglitazone treatment increased the triglyceride content of the steatotic livers of A-ZIP/F-1 and ob/ob mice, but not the “lean” livers of fat-transplanted A-ZIP/F-1 mice. In light of this evidence that rosiglitazone acts differently in steatotic livers, the effects of rosiglitazone, particularly on hepatic triglyceride levels, should be examined in humans with hepatic steatosis. PMID:11086023

Isothiocyanate-rich Moringa oleifera extract reduces weight gain, insulin resistance, and hepatic gluconeogenesis in mice.

PubMed

Waterman, Carrie; Rojas-Silva, Patricio; Tumer, Tugba Boyunegmez; Kuhn, Peter; Richard, Allison J; Wicks, Shawna; Stephens, Jacqueline M; Wang, Zhong; Mynatt, Randy; Cefalu, William; Raskin, Ilya

2015-06-01

Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo. C57BL/6L mice fed very high fat diet (VHFD) supplemented with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat mass, had improved glucose tolerance and insulin signaling, and did not develop fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced plasma insulin, leptin, resistin, cholesterol, IL-1β, TNFα, and lower hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in adipose tissue in vivo argued these are not likely primary targets for the anti-obesity and anti-diabetic effects observed. Data suggest that MICs are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert their effects by inhibiting rate-limiting steps in liver gluconeogenesis resulting in direct or indirect increase in insulin signaling and sensitivity. These conclusions suggest that MC may be an effective dietary food for the prevention and treatment of obesity and type 2 diabetes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Glycogen synthase kinase 3: more than a namesake.

PubMed

Rayasam, Geetha Vani; Tulasi, Vamshi Krishna; Sodhi, Reena; Davis, Joseph Alex; Ray, Abhijit

2009-03-01

Glycogen synthase kinase 3 (GSK3), a constitutively acting multi-functional serine threonine kinase is involved in diverse physiological pathways ranging from metabolism, cell cycle, gene expression, development and oncogenesis to neuroprotection. These diverse multiple functions attributed to GSK3 can be explained by variety of substrates like glycogen synthase, tau protein and beta catenin that are phosphorylated leading to their inactivation. GSK3 has been implicated in various diseases such as diabetes, inflammation, cancer, Alzheimer's and bipolar disorder. GSK3 negatively regulates insulin-mediated glycogen synthesis and glucose homeostasis, and increased expression and activity of GSK3 has been reported in type II diabetics and obese animal models. Consequently, inhibitors of GSK3 have been demonstrated to have anti-diabetic effects in vitro and in animal models. However, inhibition of GSK3 poses a challenge as achieving selectivity of an over achieving kinase involved in various pathways with multiple substrates may lead to side effects and toxicity. The primary concern is developing inhibitors of GSK3 that are anti-diabetic but do not lead to up-regulation of oncogenes. The focus of this review is the recent advances and the challenges surrounding GSK3 as an anti-diabetic therapeutic target.

Antidiabetic and Antioxidant Activity of Scoparia dulcis Linn.

PubMed

Mishra, M R; Mishra, A; Pradhan, D K; Panda, A K; Behera, R K; Jha, S

2013-09-01

The hypoglycaemic activity of methanol extract of Scoparia dulcis was performed on both in vitro and in vivo models along with determination of total extractable polyphenol. Methanol extract of Scoparia dulcis contains 4.9% and water extract contains 3.2% of total extractable polyphenol. The antioxidant activity showed very promising result in both the tested methods that is 2,2-diphenyl-1-picrylhydrazyl and ferric ion reducing capacity. The antioxidant activity is directly correlated to the antidiabetic potential of drug. The two enzymes (amylase and glycosidase) found in intestine are responsible for the increasing postprandial glucose in body. In vitro model was performed on these enzymes and the results showed that methanol extract of Scoparia dulcis was effective to check the postprandial glucose level. The in vivo hypoglycaemic activity of methanol extract of Scoparia dulcis was performed on streptozotocin-induced diabetes mellitus showed significant inhibition of blood glucose level as compared to control and similar to that of standard glibenclamide. The overall data potentiates the traditional value of Scoparia dulcis as an antidiabetic drug.

Catechin-loaded Eudragit microparticles for the management of diabetes: formulation, characterization and in vivo evaluation of antidiabetic efficacy.

PubMed

Meena, Kedar Prasad; Vijayakumar, Mahalingam Rajamanickam; Dwibedy, Priti S

2017-06-01

Catechin (CT) is natural molecule proved for antidiabetic activity. Clinical application of CT is highly restricted because of its low bioavailability and ineffectiveness in in vivo conditions. Therefore, the main objective of the present investigation was to formulate CT-loaded Eudragit RS 100 microparticles and evaluated for its potential against diabetes. CT microparticles showing highest entrapment efficiency of 92.3 ± 6.5% and higher percentage yield of 63.46 ± 4.3% was selected as optimised formulation. CT microparticles treated rats showed significantly lower blood glucose, cholesterol, LDL, free fatty acid and triglyceride concentrations in comparison to pristine CT-treated rats. The glucose and lipid profiles of microparticle formulation were akin to normal rats. Moreover, CT microparticles did not produce obesity even after 60 days which is a comment side effect of antidiabetic drugs. These results indicate that the CT microparticles can be applied as potential and safe carrier for the treatment of diabetes.

Important Aspects of Post-Prandial Antidiabetic Drug, Acarbose.

PubMed

Singla, Rajeev Kumar; Singh, Radha; Dubey, Ashok Kumar

2016-01-01

Acarbose, a well known and efficacious α-amylase and α-glucosidase inhibitor, is a postprandial acting antidiabetic drug. DNS-based α-amylase inhibitory assays showed that use of acarbose at concentrations above 125 µg/ml resulted in release of reducing sugar in the reaction, an unexpected observation. Objective of the present study was to design experimental strategies to address this unusual finding. Acarbose was found to be susceptible to thermo-lysis. Further, besides being an inhibitor, it could also be hydrolyzed by porcine pancreatic α-amylase, but had weaker affinity for α - amylase compared to starch. GRIP docking was done for the mechanistic analysis of the active site in the enzyme for substrate, inhibitor and, inhibitor's metabolite (K2). Interaction between acarbose and α-amylase involved significant hydrogen binding compared to that of starch, producing a stronger enzyme-inhibitor complex. Further, docking analysis led us to predict the site on α-amylase where the inhibitor (acarbose) bound more tightly, which possibly affected the binding and hydrolysis of starch exerting its effective anti-diabetic function.

Binding Energy calculation of GSK-3 protein of Human against some anti-diabetic compounds of Momordica charantia linn (Bitter melon)

PubMed Central

Hazarika, Ridip; Parida, Pratap; Neog, Bijoy; Yadav, Raj Narain Singh

2012-01-01

Diabetes is one of the major life threatening diseases worldwide. It creates major health problems in urban India. Glycogen Synthase Kinase-3 (GSK-3) protein of human is known for phosphorylating and inactivating glycogen synthase which also acts as a negative regulator in the hormonal control of glucose homeostasis. In traditional medicine, Momordica charantia is used as antidiabetic plant because of its hypoglycemic effect. Hence to block the active site of the GSK-3 protein three anti-diabetic compounds namely, charantin, momordenol & momordicilin were taken from Momordica charantia for docking study and calculation of binding energy. The aim of present investigation is to find the binding energy of three major insulin-like active compounds against glycogen synthase kinase-3 (GSK-3), one of the key proteins involved in carbohydrate metabolism, with the help of molecular docking using ExomeTM Horizon suite. The study recorded minimum binding energy by momordicilin in comparison to the others. PMID:22493531

Binding Energy calculation of GSK-3 protein of Human against some anti-diabetic compounds of Momordica charantia linn (Bitter melon).

PubMed

Hazarika, Ridip; Parida, Pratap; Neog, Bijoy; Yadav, Raj Narain Singh

2012-01-01

Diabetes is one of the major life threatening diseases worldwide. It creates major health problems in urban India. Glycogen Synthase Kinase-3 (GSK-3) protein of human is known for phosphorylating and inactivating glycogen synthase which also acts as a negative regulator in the hormonal control of glucose homeostasis. In traditional medicine, Momordica charantia is used as antidiabetic plant because of its hypoglycemic effect. Hence to block the active site of the GSK-3 protein three anti-diabetic compounds namely, charantin, momordenol & momordicilin were taken from Momordica charantia for docking study and calculation of binding energy. The aim of present investigation is to find the binding energy of three major insulin-like active compounds against glycogen synthase kinase-3 (GSK-3), one of the key proteins involved in carbohydrate metabolism, with the help of molecular docking using ExomeTM Horizon suite. The study recorded minimum binding energy by momordicilin in comparison to the others.

Diabetes and Ramadan: An Update On Use of Glycemic Therapies During Fasting

PubMed Central

Ahmed, Mohamed H.; Abdu, Tarig A. M.

2011-01-01

The fasting of Ramadan is observed by a large proportion of Muslims with diabetes. Recommendations for the management of diabetes during Ramadan were last published in 2005 by the American Diabetes Association. Several studies in this field have since been published, some addressing the use of new pharmacological agents in managing diabetes during Ramadan. The incritin memetics are potentially safe during Ramadan; the DPP4 inhibitors vildagliptin and sitagliptin provide an effective and safe therapeutic option, administered either alone or in combination with metformin or sulfonylureas. There are no published studies on the use of GLP-1 receptor agonists during Ramadan. Among the sulfonylureas, gliclazide MR (modified release) and glimepride can be safely used during Ramadan, but glibenclamide should be avoided due to the associated risk of hypoglycemia. In selected patients with type 1 and type 2 diabetes, the long-acting insulin analogues glargine and detemir, as well as the premixed insulin analogues, can be used with minimal risk of metabolic derangement or hypoglycemia; the risk is higher in type 1 diabetes. Insulin pumps can potentially empower patients with diabetes and enable safe fasting during the month of Ramadan. Further clinical trials are needed to evaluate the safety and efficacy of new antidiabetic agents and new diabetes-related technologies during Ramadan. PMID:21727749

Saxagliptin for the treatment of diabetes - a focus on safety.

PubMed

Cernea, Simona; Cahn, Avivit; Raz, Itamar

2016-05-01

The safety of agents used to treat type 2 diabetes (T2D), a chronic disease requiring life-long intervention, is of particular interest. Saxagliptin is a potent and selective DPP-4 inhibitor that has emerged as a therapeutic option for T2D. Its safety was assessed in a development program of 20 phase 2/3 randomized clinical trials and in SAVOR-TIMI 53 trial that evaluated the cardiovascular outcomes. In order to capture any further safety signals, mainly in the long-term, a post-marketing safety surveillance is ongoing. This paper discusses the tolerability and safety profile of the agent, including cardiovascular, renal, pancreatic, hepatic and bone adverse events. Saxagliptin is a safe therapeutic option for patients with T2D, with low risk of hypoglycemia and good tolerability. It demonstrated cardiovascular safety (including in patients with pre-existing cardiovascular disease and/or HF) and safety with respect to all-cause mortality and adverse events of special interest. In SAVOR-TIMI53, saxagliptin was associated with an unexpected increased risk of HF hospitalization, mainly in the first 12 months; a mechanistic explanation for this has not been found. Further research needs to elucidate the effect of antidiabetic drugs on the heart, by including biomarkers and echocardiographic sub-studies within large outcome trials.

Diabetes and Ramadan: an update on use of glycemic therapies during fasting.

PubMed

Ahmed, Mohamed H; Abdu, Tarig A M

2011-01-01

The fasting of Ramadan is observed by a large proportion of Muslims with diabetes. Recommendations for the management of diabetes during Ramadan were last published in 2005 by the American Diabetes Association. Several studies in this field have since been published, some addressing the use of new pharmacological agents in managing diabetes during Ramadan. The incritin memetics are potentially safe during Ramadan; the DPP4 inhibitors vildagliptin and sitagliptin provide an effective and safe therapeutic option, administered either alone or in combination with metformin or sulfonylureas. There are no published studies on the use of GLP-1 receptor agonists during Ramadan. Among the sulfonylureas, gliclazide MR (modified release) and glimepride can be safely used during Ramadan, but glibenclamide should be avoided due to the associated risk of hypoglycemia. In selected patients with type 1 and type 2 diabetes, the long-acting insulin analogues glargine and detemir, as well as the premixed insulin analogues, can be used with minimal risk of metabolic derangement or hypoglycemia; the risk is higher in type 1 diabetes. Insulin pumps can potentially empower patients with diabetes and enable safe fasting during the month of Ramadan. Further clinical trials are needed to evaluate the safety and efficacy of new antidiabetic agents and new diabetes-related technologies during Ramadan.

Uptake, translocation and possible biodegradation of the antidiabetic agent metformin by hydroponically grown Typha latifolia.

PubMed

Cui, Hao; Schröder, Peter

2016-05-05

The increasing load of pharmaceutical compounds has raised concerns about their potential residues in aquatic environments and ecotoxicity. Metformin (MET), a widely prescribed antidiabetic II medicine, has been detected in high concentration in sewage and in wastewater treatment effluents. An uptake and translocation study was carried out to assess the ultimate fate of MET in phytoremediation. MET was removed from media by Typha latifolia, and the removal processes followed first order kinetics. After 28 days, the removal efficiencies were in a range of 74.0±4.1-81.1±3.3%. In roots, MET concentration was increasing during the first two weeks of the experiment but thereafter decreasing. In contrast, MET concentration was continuously increasing in rhizomes and leaves. Bioaccumulation of MET in roots was much higher than in leaves and rhizomes. As degradation product of metformin in the plant, methylbiguanide (MBG) was detected whereas guanylurea was undetectable. Moreover, MBG concentration in roots was increasing with exposure time. An enzymatic degradation experiment showed the degradation rate followed the order of MET

Parkinson's Disease, Diabetes and Cognitive Impairment.

PubMed

Ashraghi, Mohammad R; Pagano, Gennaro; Polychronis, Sotirios; Niccolini, Flavia; Politis, Marios

2016-01-01

Parkinson's disease is a chronic neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulinresistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment. To review experimental and clinical evidence of underlying Parkinson's pathophysiology in common with diabetes and cognitive impairment. Anti-diabetic agents and recent patents for insulin-resistance that might be repositioned in the treatment of Parkinson's also have been included in this review. A narrative review using MEDLINE database. Common antidiabetic treatments such as DPP4 inhibitors, GLP-1 agonists and metformin have shown promise in the treatment of Parkinson's disease and cognitive impairment in animals and humans. Study of the pathophysiology of neurodegeneration common between diabetes and Parkinson's disease has given rise to new treatment possibilities. Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

Antidiabetic effect of Scoparia dulcis: effect on lipid peroxidation in streptozotocin diabetes.

PubMed

Pari, L; Latha, M

2005-03-01

Oxidative damage has been suggested to be a contributory factor in the development and complications of diabetes. The antioxidant effect of an aqueous extract of Scoparia dulcis, an indigenous plant used in Ayurvedic medicine in India was studied in rats with streptozotocin-induced diabetes. Oral administration of Scoparia dulcis plant extract (SPEt) (200 mg/kg body weight) for 3 weeks resulted in a significant reduction in blood glucose and an increase in plasma insulin. The aqueous extract also resulted in decreased free radical formation in tissues (liver and kidney) studied. The decrease in thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HPX) and increase in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and glutathione-S-transferase (GST) clearly show the antioxidant properties of SPEt in addition to its antidiabetic effect. The effect of SPEt at 200 mg/kg body weight was better than glibenclamide, a reference drug.

Cyanidin-3-glucoside isolated from mulberry fruits protects pancreatic β-cells against glucotoxicity-induced apoptosis.

PubMed

Lee, Jong Seok; Kim, Young Rae; Park, Jun Myoung; Kim, Young Eon; Baek, Nam In; Hong, Eock Kee

2015-04-01

The present study investigated the cytoprotective effects of cyanidin‑3‑glucoside (C3G), isolated from mulberry fruits, on the glucotoxicity‑induced apoptosis of pancreatic β‑cells to evaluate the antidiabetic effects of this compound. MIN6N pancreatic β‑cells were used to investigate the cytoprotective effects of C3G. In addition, the effects of C3G on the glucotoxicity‑induced apoptosis of pancreatic β‑cells was evaluated using MTT assay, immunofluorescent staining, flow cytometric and western blot analyses. The pancreatic β‑cells cultured under high glucose conditions exhibited distinct apoptotic features. C3G decreased the generation of intracellular reactive oxygen species, DNA fragmentation and the rate of apoptosis. C3G also prevented pancreatic β‑cell apoptosis induced by high glucose conditions by interfering with the intrinsic apoptotic pathways. In addition, C3G treatment resulted in increased insulin secretion compared with treatment with high glucose only. In conclusion, the results of the present study suggested that C3G obtained from mulberry fruits may be a potential phytotherapeutic agent for the prevention of diabetes.

Exubera® (inhaled insulin): an evidence-based review of its effectiveness in the management of diabetes

PubMed Central

Profit, Louise

2005-01-01

Introduction: Inadequate glycemic control contributes to the development and progression of complications, which are associated with a significant economic burden on healthcare systems. However, optimal glycemic control is difficult to sustain with oral antidiabetic agents and adherence to intensive insulin regimens is compromised by patient compliance to multiple daily injections. Therefore, alternative delivery systems are required to improve the acceptability of insulin therapy. Aims: This review assesses the evidence for the therapeutic value of inhaled insulin (Exubera®) in the management of type 1 and type 2 diabetes. Evidence review: Evidence indicates that glycemic control, as measured by plasma HbA1c levels, with Exubera is as effective as subcutaneous insulin in patients with type 1 or type 2 diabetes. There is also good evidence that Exubera provides improved patient satisfaction and ease of use compared with subcutaneous insulin. However, the cost effectiveness of Exubera and its place in therapy compared with other inhaled insulin delivery systems currently in development remain to be determined. Outcomes summary: Exubera is an alternative treatment option for the management of diabetes which provides effective glycemic control with improved patient satisfaction. PMID:22500147

Insulin-like biological activity of culinary and medicinal plant aqueous extracts in vitro.

PubMed

Broadhurst, C L; Polansky, M M; Anderson, R A

2000-03-01

To evaluate the possible effects on insulin function, 49 herb, spice, and medicinal plant extracts were tested in the insulin-dependent utilization of glucose using a rat epididymal adipocyte assay. Cinnamon was the most bioactive product followed by witch hazel, green and black teas, allspice, bay leaves, nutmeg, cloves, mushrooms, and brewer's yeast. The glucose oxidation enhancing bioactivity was lost from cinnamon, tea, witch hazel, cloves, bay leaf and allspice by poly(vinylpyrrolidone) (PVP) treatment, indicating that the active phytochemicals are likely to be phenolic in nature. The activity of sage, mushrooms, and brewers's yeast was not removed by PVP. Some products such as Korean ginseng, flaxseed meal, and basil have been reported to be effective antidiabetic agents; however, they were only marginally active in our assay. Our technique measures direct stimulation of cellular glucose metabolism, so it may be that the active phytochemicals in these plants improve glucose metabolism via other mechanisms or that this in vitro screening is not a reliable predictor of hypoglycemic effects in vivo for some products. In summary, the positive effects of specific plant extracts on insulin activity suggest a possible role of these plants in improving glucose and insulin metabolism.

Discovery of diethyl 2,5-diaminothiophene-3,4-dicarboxylate derivatives as potent anticancer and antimicrobial agents and screening of anti-diabetic activity: synthesis and in vitro biological evaluation. Part 1.

PubMed

Bozorov, Khurshed; Ma, Hai-Rong; Zhao, Jiang-Yu; Zhao, Hai-Qing; Chen, Hua; Bobakulov, Khayrulla; Xin, Xue-Lei; Elmuradov, Burkhon; Shakhidoyatov, Khusnutdin; Aisa, Haji A

2014-09-12

Series of diethyl 2,5-diaminothiophene-3,4-dicarboxylate (DDTD) derivatives: azomethines of DDTD (2a-l) have been synthesized and screened for their anticancer, antimicrobial and anti-diabetic activities. The novel synthesized compounds were characterized by (1)H, (13)C NMR, MS and FT-IR analyses. All compounds were evaluated for their antiproliferative activity against three types of cancer cell line such as T47D and MCF-7 (human breast cancer), Hela (human cervical cancer) and Ishikawa (human endometrial cancer) lines. The results showed that most compounds exhibited significant antiproliferative activity against breast cancer cells. The majority of azomethines DDTD influenced strongly against breast cancer cells T47D and MCF-7, among them compounds 2b (2.3 μM), 2c (12.1 μM), 2e (13.2 μM), 2i (14.9 μM), 2j (16.0 μM), 2k (7.1 μM), 2l (8.6 μM) manifest potent anticancer activity against cancer cell T47D than Doxorubicin (DOX, 15.5 μM). Compound 2j has shown potent activity on all three types of cancer cells concurrently and IC50 values were considerably low in comparison with positive control DOX. In addition, all compounds were tested for antimicrobial activity against Staphylococcus aureus ATCC 6538 (Gram positive bacteria), Escherichia coli ATCC 11229 (Gram negative bacteria) and Candida albicans ATCC 10231 (Fungi) strains and 2j which contains in the ring nitrofurfural fragment, showed the highest effect on the three species of microbial pathogens simultaneously. Some compounds induced enzymatic inhibition in a concentration-dependent manner on PTP-1B inhibitor. Copyright © 2014. Published by Elsevier Masson SAS.

Cardiovascular risk associated with acarbose versus metformin as the first-line treatment in patients with type 2 diabetes: a nationwide cohort study.

PubMed

Chang, Chia-Hsuin; Chang, Yi-Cheng; Lin, Jou-Wei; Chen, Shu-Ting; Chuang, Lee-Ming; Lai, Mei-Shu

2015-03-01

Metformin is the first-line oral therapy for type 2 diabetes with proven benefits against cardiovascular risk. Recent evidence suggested that acarbose might be similar to metformin in glucose-lowering efficacy and cardiovascular risk reduction. Therefore, international guidelines have suggested the use of acarbose as alternative first-line antidiabetic therapy. To compare the cardiovascular outcomes in the first-line users of acarbose vs metformin. DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: A nationwide cohort study was conducted by analyzing the Taiwan National Health Insurance (NHI) Database. A total of 17,366 acarbose initiators and 230,023 metformin initiators were identified between January 1, 2009 and December 31, 2010. The primary outcome is hospitalization due to any cardiovascular events, including acute myocardial infarction, congestive heart failure, and ischemic stroke. The propensity score method was used to adjust for baseline differences between the two groups. Patients were followed from drug initiation to the earliest of outcome occurrence, death or disenrollment from NHI, or study termination. In intention-to-treat analyses, acarbose was associated with a higher risk of any cardiovascular event (adjusted hazard ratio [HR]: 1.05; 95% confidence interval [CI], 1.01-1.09), heart failure (HR, 1.08; 95% CI, 1.00-1.16), and ischemic stroke (HR, 1.05, 95% CI, 1.00-1.10) than metformin. No significant difference in risk was found in subgroups of patients with or without underlying hypertension, ischemic heart disease, or cerebrovascular disease. Similar results were found in auxiliary as-treated analyses or analyses stratified by propensity score quintiles. Our data do not support that acarbose has a cardio-protective effect similar to metformin as a first-line antidiabetic agent.

Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes.

PubMed

Albarracin, Cesar A; Fuqua, Burcham C; Evans, Joseph L; Goldfine, Ira D

2008-01-01

Chromium and biotin play essential roles in regulating carbohydrate metabolism. This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of the combination of chromium picolinate and biotin on glycaemic control. Four hundred and forty-seven subjects with poorly controlled type 2 diabetes (HbA(1c) > or = 7.0%) were enrolled and received either chromium picolinate (600 microg Cr(+3)) with biotin (2 mg), or matching placebo, for 90 days in combination with stable oral anti-diabetic agents (OADs). Major endpoints were reductions in HbA(1c), fasting glucose, and lipids. Safety and tolerability were assessed. Change in HbA(1c) was significantly different between treatment groups (p = 0.03). HbA(1c) in the chromium picolinate/biotin group decreased 0.54%. The decrease in HbA(1c) was most pronounced in chromium picolinate/biotin subjects whose baseline HbA(1c) > or = 10%, and highly significant when compared with placebo (-1.76% vs - 0.68%; p = 0.005). Fasting glucose levels were reduced in the entire chromium picolinate/biotin group versus placebo (-9.8 mg/dL vs 0.7 mg/dL; p = 0.02). Reductions in fasting glucose were also most marked in those subjects whose baseline HbA(1c) > or = 10.0%, and significant when compared to placebo (-35.8 mg/dL vs. 16.2 mg/dL; p = 0.01). Treatment was well tolerated with no adverse effects dissimilar from placebo. These results suggest that the chromium picolinate/biotin combination, administered as an adjuvant to current prescription anti-diabetic medication, can improve glycaemic control in overweight to obese individuals with type 2 diabetes; especially those patients with poor glycaemic control on oral therapy. 2007 John Wiley & Sons, Ltd

Insulin-secretagogue, antihyperlipidemic and other protective effects of gallic acid isolated from Terminalia bellerica Roxb. in streptozotocin-induced diabetic rats.

PubMed

Latha, R Cecily Rosemary; Daisy, P

2011-01-15

Diabetes mellitus causes derangement of carbohydrate, protein and lipid metabolism which eventually leads to a number of secondary complications. Terminalia bellerica is widely used in Indian medicine to treat various diseases including diabetes. The present study was carried out to isolate and identify the putative antidiabetic compound from the fruit rind of T. bellerica and assess its chemico-biological interaction in experimental diabetic rat models. Bioassay guided fractionation was followed to isolate the active compound, structure was elucidated using (1)H and (13)C NMR, IR, UV and mass spectrometry and the compound was identified as gallic acid (GA). GA isolated from T. bellerica and synthetic GA was administered to streptozotocin (STZ)-induced diabetic male Wistar rats at different doses for 28 days. Plasma glucose level was significantly (p<0.05) reduced in a dose-dependent manner when compared to the control.Histopathological examination of the pancreatic sections showed regeneration of β-cells of islets of GA-treated rats when compared to untreated diabetic rats. In addition, oral administration of GA (20mg/kg bw) significantly decreased serum total cholesterol, triglyceride, LDL-cholesterol, urea, uric acid, creatinine and at the same time markedly increased plasma insulin, C-peptide and glucose tolerance level. Also GA restored the total protein, albumin and body weight of diabetic rats to near normal. Thus our findings indicate that gallic acid present in fruit rind of T. bellerica is the active principle responsible for the regeneration of β-cells and normalizing all the biochemical parameters related to the patho-biochemistry of diabetes mellitus and hence it could be used as a potent antidiabetic agent. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Does dapagliflozin regress left ventricular hypertrophy in patients with type 2 diabetes? A prospective, double-blind, randomised, placebo-controlled study.

PubMed

Brown, Alexander J M; Lang, Chim; McCrimmon, Rory; Struthers, Allan

2017-08-23

Patients with diabetes have a two to fourfold increased risk for development of and death from cardiovascular disease [CVD]. The current oral hypoglycaemic agents result in limited reduction in this cardiovascular risk. Sodium glucose linked co-transporter type 2 [SGLT2] inhibitors are a relatively new class of antidiabetic agent that have been shown to have potential cardiovascular benefits. In support of this, the EMPA-REG trial showed a striking 38% and 35% reduction in cardiovascular mortality and heart failure [HF] hospitalisation respectively. The exact mechanism (s) responsible for these effects remain (s) unclear. One potential mechanism is regression of Left ventricular hypertrophy (LVH). The DAPA-LVH trial is a prospective, double-blind, randomised, placebo-controlled 'proof of concept' single-centre study that has been ongoing since January 2017. It is designed specifically to assess whether the SGLT2 inhibitor dapagliflozin regresses left ventricular [LV] mass in patients with diabetes and left ventricular hypertrophy [LVH]. We are utilising cardiac and abdominal magnetic resonance imaging [MRI] and ambulatory blood pressure monitoring to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard care over a 1 year observation period. The primary endpoint is to detect the changes in LV mass. The secondary outcomes are to assess the changes in, LV volumes, blood pressure, weight, visceral and subcutaneous fat. This trial will be able to determine if SGLT2 inhibitor therapy reduces LV mass in patient with diabetes and LVH thereby strengthening their position as oral hypoglycaemic agents with cardioprotective benefits. Clinical Trials.gov: NCT02956811 . Registered November 2016.

The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial.

PubMed

Singer, Gregory M; Geohas, Jeff

2006-12-01

Preclinical studies have shown that the combination of chromium picolinate and biotin significantly enhances glucose uptake in skeletal muscle cells and enhances glucose disposal. The present pilot study was conducted to determine if supplementation with chromium picolinate and biotin can improve glycemic control in patients with type 2 diabetes mellitus with suboptimal glycemic control despite use of oral antihyperglycemic agents. Forty-three subjects with impaired glycemic control (2-h glucose >200 mg/dL; glycated hemoglobin >or=7%), despite treatments with oral antihyperglycemic agents, were randomized to receive 600 microg of chromium as chromium picolinate and biotin (2 mg/day) (Diachrome(, Nutrition 21, Inc., Purchase, NY) in addition to their prestudy oral antihyperglycemic agent therapy. Measurements of glycemic control and blood lipids were taken at baseline and after 4 weeks. After 4 weeks, there was a significantly greater reduction in the total area under the curve for glucose during the 2-h oral glucose tolerance test for the treatment group (mean change -9.7%) compared with the placebo group (mean change +5.1%, P < 0.03). Significantly greater reductions were also seen in fructosamine (P < 0.03), triglycerides (P < 0.02), and triglycerides/ high-density lipoprotein cholesterol ratio (P < 0.05) in the treatment group. No significant adverse events were attributed to chromium picolinate and biotin supplementation. This pilot study demonstrates that supplementation with a combination of chromium picolinate and biotin in poorly controlled patients with diabetes receiving antidiabetic therapy improved glucose management and several lipid measurements. Chromium picolinate/ biotin supplementation may represent an effective adjunctive nutritional therapy to people with poorly controlled diabetes with the potential for improving lipid metabolism.

Antioxidant and antidiabetic properties of tartary buckwheat rice flavonoids after in vitro digestion*

PubMed Central

Bao, Tao; Wang, Ye; Li, Yu-ting; Gowd, Vemana; Niu, Xin-he; Yang, Hai-ying; Chen, Li-shui; Chen, Wei; Sun, Chong-de

2016-01-01

Oxidative stress and diabetes have a tendency to alter protein, lipid, and DNA moieties. One of the strategic methods used to reduce diabetes-associated oxidative stress is to inhibit the carbohydrate-digesting enzymes, thereby decreasing gastrointestinal glucose production. Plant-derived natural antioxidant molecules are considered a therapeutic tool in the treatment of oxidative stress and diabetes. The objective of this study was to identify tartary buckwheat rice flavonoids and evaluate the effect of in vitro digestion on their antioxidant and antidiabetic properties. High performance liquid chromatography (HPLC) analysis indicated the presence of rutin as a major component and quercitrin as a minor component of both digested and non-digested flavonoids. Both extracts showed a significant antioxidant capacity, but digested flavonoids showed reduced activity compared to non-digested. There were some decreases of the antioxidant activities (2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS), 2,2-diphenyl-1-picrylhydrazy (DPPH) radical, and ferric reducing antioxidant power (FRAP)) of digested tartary buckwheat rice flavonoids compared with non-digested. Flavonoids from both groups significantly inhibited reactive oxygen species (ROS) production and α-glucosidase activity. Both digested and non-digested flavonoids markedly increased glucose consumption and glycogen content in HepG2 cells. Tartary buckwheat rice flavonoids showed appreciable antioxidant and antidiabetic properties, even after digestion. Tartary buckwheat rice appears to be a promising functional food with potent antioxidant and antidiabetic properties. PMID:27921399

Antidiabetic effect of Cinnamomum cassia and Cinnamomum zeylanicum in vivo and in vitro.

PubMed

Verspohl, Eugen J; Bauer, Katrin; Neddermann, Eckhard

2005-03-01

Rats were given Cinnamomum cassia bark or extracts from Cinnamomum cassia and zeylanicum to evaluate blood glucose and plasma insulin levels in rats under various conditions. The cassia extract was superior to the zeylanicum extract. The cassia extract was slightly more efficacious than the equivalent amount of Cassia bark. A decrease in blood glucose levels was observed in a glucose tolerance test (GTT), whereas it was not obvious in rats that were not challenged by a glucose load. The elevation in plasma insulin was direct since a stimulatory in vitro effect of insulin release from INS-1 cells (an insulin secreting cell line) was observed. Thus the cassia extract has a direct antidiabetic potency. Copyright 2005 John Wiley & Sons, Ltd.

Immunomodulatory and Antidiabetic Effects of a New Herbal Preparation (HemoHIM) on Streptozotocin-Induced Diabetic Mice.

PubMed

Kim, Jong-Jin; Choi, Jina; Lee, Mi-Kyung; Kang, Kyung-Yun; Paik, Man-Jeong; Jo, Sung-Kee; Jung, Uhee; Park, Hae-Ran; Yee, Sung-Tae

2014-01-01

Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia japonica Miyabe) was developed to protect immune, hematopoietic, and self-renewal tissues against radiation. This study determined whether or not HemoHIM could alter hyperglycemia and the immune response in diabetic mice. Both nondiabetic and diabetic mice were orally administered HemoHIM (100 mg/kg) once a day for 4 weeks. Diabetes was induced by single injection of streptozotocin (STZ, 200 mg/kg, i.p.). In diabetic mice, HemoHIM effectively improved hyperglycemia and glucose tolerance compared to the diabetic control group as well as elevated plasma insulin levels with preservation of insulin staining in pancreatic β-cells. HemoHIM treatment restored thymus weight, white blood cells, lymphocyte numbers, and splenic lymphocyte populations (CD4(+) T and CD8(+) T), which were reduced in diabetic mice, as well as IFN-γ production in response to Con A stimulation. These results indicate that HemoHIM may have potential as a glucose-lowering and immunomodulatory agent by enhancing the immune function of pancreatic β-cells in STZ-induced diabetic mice.

Characterization of Momordica charantia L. polysaccharide and its protective effect on pancreatic cells injury in STZ-induced diabetic mice.

PubMed

Zhang, Cong; Chen, Hongman; Bai, Weiqi

2018-04-10

A polysaccharide with a molecular weight of 13,029Da was isolated from Momordica charantia (MCP) fruit and purified by ion-exchange and size-exclusion chromatography. The isolated polysaccharide MCPIIa contained L-Rha, D-GalA, D-Gal, D-Xyl, L-Ara in a molar ratio of 12:3.05:19.89:5.95:56. IR spectrum and NMR studies indicated that the MCPIIa sugar units were linked, via β-glycosidic bonds, to a large number of arabinofuranose, glucuronic acid, and xylopyranosyl residues. In addition, the hypoglycemic effect of MCPIIa was investigated in streptozotocin (STZ)-induced diabetic mice. After STZ-induction, MCPIIa (100, 200, or 300mg/kg body weight) was administered orally, once daily, for 28days. Glycemia in STZ-diabetogenic mice was significantly reduced, and compared with diabetes mellitus (DM) mice, serum insulin concentration increased significantly, following MCPIIa administration. Transmission electron microscopy showed an alleviation of STZ-lesions in pancreatic tissue from mice treated with MCPIIa. These results indicate that MCPIIa may be useful as an anti-diabetic agent. Copyright © 2018 Elsevier B.V. All rights reserved.

Peptide based therapeutics and their use for the treatment of neurodegenerative and other diseases.

PubMed

Baig, Mohammad Hassan; Ahmad, Khurshid; Saeed, Mohd; Alharbi, Ahmed M; Barreto, George E; Ashraf, Ghulam Md; Choi, Inho

2018-04-17

Bioactive peptides are actively involved in different biological functions and importantly contribute to human health, and the use of peptides as therapeutics has a long successful history in disease management. A number of peptides have wide-ranging therapeutic effects, such as antioxidant, antimicrobial, and antithrombotic effects. Neurodegenerative diseases are typically caused by abnormal aggregations of proteins or peptides, and the depositions of these aggregates in or on neurons, disrupt signaling and eventually kill neurons. During recent years, research on short peptides has advanced tremendously. This review offers a brief introduction to peptide based therapeutics and their application in disease management and provides an overview of peptide vaccines, and toxicity related issues. In addition, the importance of peptides in the management of different neurodegenerative diseases and their therapeutic applications is discussed. The present review provides an understanding of peptides and their applications for the management of different diseases, but with focus on neurodegenerative diseases. The role of peptides as anti-cancer, antimicrobial and antidiabetic agents has also been discussed. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Coriolus versicolor aqueous extract ameliorates insulin resistance with PI3K/Akt and p38 MAPK signaling pathways involved in diabetic skeletal muscle.

PubMed

Xian, Hui-Min; Che, Hui; Qin, Ying; Yang, Fan; Meng, Song-Yan; Li, Xiao-Guang; Bai, Yun-Long; Wang, Li-Hong

2018-03-01

Patients with type 2 diabetes mellitus (T2DM) are usually with poor immunity and easier to suffer from cancer and microbial infections. Herein, we report an efficient anti-diabetic medicinal mushroom, Coriolus versicolor (CV). This study aimed to investigate the anti-diabetic and anti-insulin-resistance effects of CV aqueous extract in myoblasts (L6 cells) and skeletal muscle of T2DM rat. Our results showed that CV extract treatment significantly reduced blood glucose levels of T2DM rats, whereas CV extract increased glucose consumption in insulin resistant L6 cells. Besides, the translocation and expression of glucose transporter 4 were enhanced by CV extract, which indicated that CV extract was effective in diabetic skeletal muscle. Moreover, CV extract treatments resulted in remarkable anti-insulin-resistance effects, which was reflected by the change of gene and protein expression levels in PI3K/Akt and p38 MAPK pathways. PI3K inhibitor, LY29004, and p38 MAPK inhibitor, SB203580 confirmed it further. In conclusion, our results demonstrated that the CV extract exhibited anti-diabetic and anti-insulin-resistance effects in diabetic skeletal muscle, and the effects were mediated by PI3K/Akt and p38 MAPK pathways. These findings are remarkable when considering the use of commercially available CV by diabetic patients who also suffer from cancer or microbial infections. Copyright © 2017 John Wiley & Sons, Ltd.

Cookies elaborated with oat and common bean flours improved serum markers in diabetic rats.

PubMed

Pérez-Ramírez, Iza F; Becerril-Ocampo, Laura J; Reynoso-Camacho, Rosalía; Herrera, Mayra D; Guzmán-Maldonado, S Horacio; Cruz-Bravo, Raquel K

2018-02-01

Common beans have been associated with anti-diabetic effects, due to its high content of bioactive compounds. Nevertheless, its consumption has decreased worldwide. Therefore, there is an increasing interest in the development of novel functional foods elaborated with common beans. The aim of this study was to evaluate the anti-diabetic effect of oat-bean flour cookies, and to analyze its bioactive composition, using commercial oat-wheat cookies for comparative purposes. Oat-bean cookies (1.2 g kg -1 ) slightly decreased serum glucose levels (∼1.1-fold) and increased insulin levels (∼1.2-fold) in diabetic rats, reducing the hyperglycemic peak in healthy rats (∼1.1-fold). Oat-bean cookies (0.8 and 1.2 g kg -1 ) exerted a greater hypolipidemic effect than commercial oat-wheat cookies (1.2 g kg -1 ), as observed in decreased serum triglycerides and low-density lipoprotein cholesterol. Furthermore, the supplementation with 1.2 g kg -1 oat-bean cookies decreased atherogenic index and serum C-reactive protein levels, suggesting their cardioprotective potential. The beneficial effect of oat-bean cookies was associated with their high content of dietary fiber and galacto oligosaccharides, as well as chlorogenic acid, rutin, protocatechuic acid, β-sitosterol and soyasaponins. These results suggest that common beans can be used as functional ingredients for the elaboration of cookies with anti-diabetic effects. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Plants used to treat diabetes in Sri Lankan Siddha Medicine - An ethnopharmacological review of historical and modern sources.

PubMed

Sathasivampillai, Saravanan V; Rajamanoharan, Pholtan R S; Munday, Michael; Heinrich, Michael

2017-02-23

In recent decades diabetes mellitus has become a considerable health problem in countries like Sri Lanka and results in an increasing economic burden hampering the social and economic development of these countries. About 60% to 70% of the rural population in Sri Lanka rely on indigenous medicinal systems as their main source for primary health care. Siddha (Tamil) Medicine is one of the four Sri Lankan traditional medicinal systems and it is practised mostly in the eastern and northern provinces of Sri Lanka where the majority of Tamils reside. The foundation of this study is a documentation of plant species recorded in historical and modern Sri Lankan Siddha Medical documents used to treat diabetes. Based on the systematic documentation and analysis of Siddha concepts about diabetes and its signs and preparations used to treat diabetes in Sri Lankan Siddha Medicine, the plant species included in these preparations (excluding globally or very widely used, very well studied species) were evaluated in terms of the current state-of-the-art about these species' pharmacology and effectiveness in order to lay a foundation for their further development. Historic and modern Sri Lankan university texts books in Tamil were used as sources for information on diabetes Siddha concepts and antidiabetic Sri Lankan Siddha Medicine preparations. Information on the known antidiabetic effects of extracts and compounds obtained from these species were used in order to assess the current state of the art of these species. Information of ingredients, preparation methods, amount of ingredients used, and dosages of 60 antidiabetic Sri Lankan Siddha Medicine preparations were obtained. Animal parts including marine organisms, inorganic substances, and plants are the three types of ingredients used. Overall 171 plant species in 73 families were documented. Senna auriculata (L.) Roxb. (Fabaceae) was identified as the most frequently cited species. Globally distributed and very well studied plants were excluded in the pharmacological and clinical literature review which includes 123 plant species. The majority (48%) of the plant species reviewed were studied up to in vivo level as the current maximum level of scientific evidence available. Followed by 41% of species have not been studied for antidiabetic activities or did not show antidiabetic activity. Moreover, 6% and 5% were studied up to in vitro and in clinical levels, respectively. The majority of the species were studied only in the models that represent type 1 diabetes. This is the first study systematically assessing the importance of preparations and plants used in antidiabetic Sri Lankan Siddha Medicine preparations. Antidiabetic plants are a crucial health care resource in Sri Lankan Siddha Medicine. This study also identified a wide range of methodological problems in the studies conducted so far. More and better type 2 diabetes models should be employed in future studies. This comprehensive review creates the basis for a more systematic study of these local resources. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Blood Glucose Reduction by Diabetic Drugs with Minimal Hypoglycemia Risk for Cardiovascular Outcomes: Evidence from Meta-regression Analysis of Randomized Controlled Trials.

PubMed

Huang, Chi-Jung; Wang, Wei-Ting; Sung, Shih-Hsien; Chen, Chen-Huan; Lip, Gregory Yh; Cheng, Hao-Min; Chiang, Chern-En

2018-05-02

To investigate the effects of blood glucose control with antihyperglycemic agents with minimal hypoglycemia risk on cardiovascular outcomes in patients with type 2 diabetes (T2D). Randomized controlled trials (RCTs) comparing the relative efficacy and safety of antidiabetic drugs with less hypoglycemia risk were comprehensively searched in MEDLINE, Embase, and the Cochrane Library up to January 27, 2018. Mixed-effects meta-regression analysis was conducted to explore the relationship between haemoglobin A1c (HbA1c) reduction and the risk of major adverse cardiovascular events (MACE), myocardial infarction, stroke, cardiovascular death, all-cause death, and hospitalization for heart failure. Ten RCTs comprising 92400 participants with T2D were included and provided information on 9773 MACE during a median follow-up of 2.6 years. The mean HbA1c concentration was 0.42% lower (median, 0.27-0.86%) for participants given antihyperglycemic agents than those given placebo. The meta-regression analysis demonstrated that HbA1c reduction was significantly associated with a decreased risk of MACE (β value, -0.39 to -0.55; P<0.02) even after adjusting for each of the following possible confounding factors including age, sex, baseline HbA1c, duration of follow-up, difference in achieved systolic blood pressure, difference in achieved body weight, or risk difference in hypoglycemia. Lowering HbA1c by 1% conferred a significant risk reduction of 30% (95% CI, 17-40%) for MACE. By contrast, the meta-regression analysis for trials using conventional agents failed to demonstrate a significant relationship between achieved HbA1c difference and MACE risk (P>0.74). Compared with placebo, newer T2D agents with less hypoglycemic hazard significantly reduced the risk of MACE. The MACE reduction seems to be associated with HbA1c reduction in a linear relationship. This article is protected by copyright. All rights reserved.

Combination of SGLT-2 inhibitors and GLP-1 receptor agonists: potential benefits in surrogate and hard endpoints.

PubMed

Doumas, Michael; Imprialos, Κonstantinos; Stavropoulos, Konstantinos; Reklou, Andromachi; Sachinidis, Alexandros; Athyros, Vasilios G

2018-06-03

The treatment of type 2 diabetes mellitus (T2DM) is complex; only few patients successfully attain glycemic targets with monotherapy, most requiring drug combination therapy. The goal of this review was to identify in PubMed the complimentary ways of action leading to clinical benefit (in lowering HbA1c, body weight, renal, and cardiac risk factors and events) of the combination of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA). SGLT2i, an emerging class of antidiabetic agents with an insulin-independent mechanism of action, are suitable for use in combination with any other class of antidiabetics, including insulin. The use of SGLT2i causes a reduction in cardiovascular disease (CVD) morbidity (mainly heart failure-HF) as well as total and CVD mortality. Besides insulin, SGLT2i may also be combined with incretin-based therapies, such as GLP-1 RA. The later appear to reduce the rate or the progression of both macrovascular (mainly myocardial infarction-MI and stroke) and microvascular complications of DM, having a beneficial effect on all-cause mortality and CVD mortality, as well as CVD events. SGLT2i and GLP-1 RA may have a synergic effect on glucose reduction, weight reduction, renal impairment (both an independent lethal disease and a CVD risk factor) improvement, and cardiac event reduction, because the first reduces HF and related events and the second decreases CVD risk (mainly MI and stroke). Both also reduce total mortality, especially when combined with a statin. The combination of metformin with SGLT2i, GLP-1 RA, and a potent statin, in high CVD risk patients with DM, is expected to substantially reduce CVD mortality and morbidity, improving the quality of life of patients with DM at the same time. Prospective studies are needed to confirm this finding. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparative Effects of Some Medicinal Plants: Anacardium occidentale, Eucalyptus globulus, Psidium guajava, and Xylopia aethiopica Extracts in Alloxan-Induced Diabetic Male Wistar Albino Rats.

PubMed

Okpashi, Victor Eshu; Bayim, Bayim Peter-Robins; Obi-Abang, Margaret

2014-01-01

Insulin therapy and oral antidiabetic agents/drugs used in the treatment of diabetes mellitus have not sufficiently proven to control hyperlipidemia, which is commonly associated with the diabetes mellitus. Again the hopes that traditional medicine and natural plants seem to trigger researchers in this area is yet to be discovered. This research was designed to compare the biochemical effects of some medicinal plants in alloxan-induced diabetic male Wistar rats using named plants that are best at lowering blood glucose and hyperlipidemia and ameliorating other complications of diabetes mellitus by methods of combined therapy. The results obtained showed 82% decrease in blood glucose concentration after the 10th hour to the fortieth hour. There was significant increase P < 0.05 in the superoxide dismutase activity of the test group administered 100 mg/kg of A. Occidentale. There was no significant difference P > 0.05 recorded in the glutathione peroxidase activity of E. globulus (100 mg/kg) when compared to the test groups of P. guajava (250 mg/kg) and X. aethiopica (250 mg/kg). Catalase activity showed significant increase P < 0.05 in the catalase activity, compared to test groups. While at P > 0.05, there was no significant difference seen between test group and treated groups. Meanwhile, degree of significance was observed in other parameters analysed. The biochemical analysis conducted in this study showed positive result, attesting to facts from previous works. Though these individual plants extracts exhibited significant increase in amelorating diabetes complication and blood glucose control compared to glibenclamide, a synthetic antidiabetic drug. Greater performance was observed in the synergy groups. Therefore, a poly/combined formulation of these plants extracts yielded significant result as well as resolving some other complications associated with diabetics.

Comparative Effects of Some Medicinal Plants: Anacardium occidentale, Eucalyptus globulus, Psidium guajava, and Xylopia aethiopica Extracts in Alloxan-Induced Diabetic Male Wistar Albino Rats

PubMed Central

Okpashi, Victor Eshu; Bayim, Bayim Peter-Robins; Obi-Abang, Margaret

2014-01-01

Insulin therapy and oral antidiabetic agents/drugs used in the treatment of diabetes mellitus have not sufficiently proven to control hyperlipidemia, which is commonly associated with the diabetes mellitus. Again the hopes that traditional medicine and natural plants seem to trigger researchers in this area is yet to be discovered. This research was designed to compare the biochemical effects of some medicinal plants in alloxan-induced diabetic male Wistar rats using named plants that are best at lowering blood glucose and hyperlipidemia and ameliorating other complications of diabetes mellitus by methods of combined therapy. The results obtained showed 82% decrease in blood glucose concentration after the 10th hour to the fortieth hour. There was significant increase P < 0.05 in the superoxide dismutase activity of the test group administered 100 mg/kg of A. Occidentale. There was no significant difference P > 0.05 recorded in the glutathione peroxidase activity of E. globulus (100 mg/kg) when compared to the test groups of P. guajava (250 mg/kg) and X. aethiopica (250 mg/kg). Catalase activity showed significant increase P < 0.05 in the catalase activity, compared to test groups. While at P > 0.05, there was no significant difference seen between test group and treated groups. Meanwhile, degree of significance was observed in other parameters analysed. The biochemical analysis conducted in this study showed positive result, attesting to facts from previous works. Though these individual plants extracts exhibited significant increase in amelorating diabetes complication and blood glucose control compared to glibenclamide, a synthetic antidiabetic drug. Greater performance was observed in the synergy groups. Therefore, a poly/combined formulation of these plants extracts yielded significant result as well as resolving some other complications associated with diabetics. PMID:25525518

Evaluation of antioxidant, antibacterial, and antidiabetic potential of two traditional medicinal plants of India: Swertia cordata and Swertia chirayita.

PubMed

Roy, Priyanka; Abdulsalam, Fatima I; Pandey, D K; Bhattacharjee, Aniruddha; Eruvaram, Naveen Reddy; Malik, Tabarak

2015-06-01

Swertia cordata and Swertia chirayita are temperate Himalayan medicinal plants used as potent herbal drugs in Indian traditional systems of medicine (Ayurvedic, Unani and Siddha). Assessment of Antioxidant, antibacterial, and antidiabetic potential of Swertia cordata and Swertia chirayita. Phytochemicals of methanolic and aqueous extracts of the two Swertia species were analyzed. The antioxidant potential of all the extracts was assessed by measuring total phenolic content, total flavonoid content and free radical scavenging potential was assessed by 1,1-diphenyl-2-picrilhydrazyl (DPPH) assay, antibacterial activity was assessed against various pathogenic and nonpathogenic bacteria in vitro by Kirby-Bauer agar well diffusion method and antidiabetic activity was assessed by α-amylase inhibition. Methanolic leaf extracts of both the species of Swertia contain significant antibacterial as well as anti-diabetic potential, whereas methanolic root extracts of both species were found to have potential antioxidant activity. However, Swertia chirayita showed better activities than Swertia cordata although both species have good reputation in traditional Indian medicine. Both the species are having high medicinal potential in terms of their antioxidant, antibacterial and antidiabetic activities. Studies are required to further elucidate antioxidant, anti-diabetic and antibacterial potentials using various in-vitro, in-vivo biochemical and molecular biology techniques.

Evaluation of antioxidant, antibacterial, and antidiabetic potential of two traditional medicinal plants of India: Swertia cordata and Swertia chirayita

PubMed Central

Roy, Priyanka; Abdulsalam, Fatima I.; Pandey, D. K.; Bhattacharjee, Aniruddha; Eruvaram, Naveen Reddy; Malik, Tabarak

2015-01-01

Background: Swertia cordata and Swertia chirayita are temperate Himalayan medicinal plants used as potent herbal drugs in Indian traditional systems of medicine (Ayurvedic, Unani and Siddha). Objective: Assessment of Antioxidant, antibacterial, and antidiabetic potential of Swertia cordata and Swertia chirayita. Materials and Methods: Phytochemicals of methanolic and aqueous extracts of the two Swertia species were analyzed. The antioxidant potential of all the extracts was assessed by measuring total phenolic content, total flavonoid content and free radical scavenging potential was assessed by 1,1-diphenyl-2-picrilhydrazyl (DPPH) assay, antibacterial activity was assessed against various pathogenic and nonpathogenic bacteria in vitro by Kirby-Bauer agar well diffusion method and antidiabetic activity was assessed by α-amylase inhibition. Results: Methanolic leaf extracts of both the species of Swertia contain significant antibacterial as well as anti-diabetic potential, whereas methanolic root extracts of both species were found to have potential antioxidant activity. However, Swertia chirayita showed better activities than Swertia cordata although both species have good reputation in traditional Indian medicine. Conclusion: Both the species are having high medicinal potential in terms of their antioxidant, antibacterial and antidiabetic activities. Studies are required to further elucidate antioxidant, anti-diabetic and antibacterial potentials using various in-vitro, in-vivo biochemical and molecular biology techniques. PMID:26109789

Standardized chungkookjang, short-term fermented soybeans with Bacillus lichemiformis, improves glucose homeostasis as much as traditionally made chungkookjang in diabetic rats

PubMed Central

Yang, Hye Jeong; Kim, Hyun Jin; Kim, Min Jung; Kang, Suna; Kim, Da Sol; Daily, James W.; Jeong, Do Youn; Kwon, Dae Young; Park, Sunmin

2013-01-01

As the traditional homemade chungkookjang is replaced by standardized chungkookjang fermented by inoculating Bacillus spp., it is desirable to maintain the anti-diabetic efficacy of the most potent traditional varieties. Preliminary in vitro research suggested that anti-diabetic efficacy can be achieved by using B. lichemiformis as a starter and fermenting for 48 h. Experimental type 2 diabetic male rats induced by partial pancreatectomy and high fat diets were administered either control diet, 10% cooked soybeans, 10% traditional chungkookjang with potent anti-diabetic efficacy, or standardized chungkookjang fermented with B. lichemiformis for 48 h. Rats were fed their respective diets for 8 weeks after surgery. Cooked soybeans as well as both chungkookjangs partially restored fasting serum glucose concentrations, but only the chungkoojangs increased fasting insulin levels. That trend was also seen in the glucose-stimulated insulin secretion during hyperglycemic clamp and was explained by the greater β-cell mass and BrdU incorporation indicating increased proliferation of β-cells. The euglycemic hyperinsulinemic clamp indicated that all soy products improved insulin sensitivity. Phosphorylation of Akt and AMPK in the liver increased in an ascending order of the control, cooked soybeans, traditional chungkookjang and standardized chungkookjang while PEPCK expression was lowered in a descending order of the control, cooked soybeans, traditional chungkookjang and standardized chungkookjang. These results indicate that standardized chungkookjang is most effective for improving hepatic insulin signaling. In conclusion, chungkookjang fermented with B. lichemiformis retains the anti-diabetic properties of the most efficacious traditional chungkookjang and it may be even more effective for improving insulin function than traditionally prepared chungkookjang. PMID:23341698

Drug-drug interactions between immunosuppressants and antidiabetic drugs in the treatment of post-transplant diabetes mellitus.

PubMed

Vanhove, Thomas; Remijsen, Quinten; Kuypers, Dirk; Gillard, Pieter

2017-04-01

Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT)-2 inhibitors. Currently available data, although limited, suggest that these increases are modest and, particularly with regard to gliptins and SGLT-2 inhibitors, unlikely to result in hypoglycemia. The interaction with repaglinide is more pronounced but does not preclude concomitant use if repaglinide dose is gradually titrated. Mycophenolate mofetil and azathioprine do not engage in DDIs with any antidiabetic drug. Although calcineurin inhibitors (CNIs) and mammalian target of rapamycin inhibitors (mTORi) are intrinsically prone to DDIs, their disposition is not influenced by metformin, pioglitazone, sulfonylureas (except possibly glyburide) or insulin. An effect of gliptins on the disposition of CNIs and mTORi is unlikely, but has not been definitively ruled out. Based on their disposition profiles, glyburide and canagliflozin could affect CNI and mTORi disposition although this requires further study. Finally, delayed gastric emptying as a result of glucagon-like peptide-1 agonists seems to have a limited, but not necessarily negligible effect on CNI disposition. Copyright © 2016 Elsevier Inc. All rights reserved.

Food and Insulin Effect on QT/QTC Interval of ECG

ClinicalTrials.gov

2014-08-19

Effects of Different Meals on the QT/QTc Interval; Insulin and Oral Hypoglycemic [Antidiabetic] Drugs Causing Adverse Effects in Therapeutic Use; C-Peptide Effects on the QT/QTc Interval; Moxifloxacin ECG Profile in Fed and Fasted State; Japanese vs. Caucasian TQT Comparison

Pharmacological importance of sulphated polysaccharide carrageenan from red seaweed Kappaphycus alvarezii in comparison with commercial carrageenan.

PubMed

Suganya, Arumugampillai Manimehalai; Sanjivkumar, Muthusamy; Chandran, Manohar Navin; Palavesam, Arunachalam; Immanuel, Grasian

2016-12-01

Pharmacological properties of native carrageenan (κ) extracted from Kappaphycus alvarezii and commercial carrageenan (Sigma-Aldrich) were evaluated using in vitro antioxidant, anticancer and antidiabetic studies. Phytochemical analysis of native and commercial carrageenans showed the presence of alkaloids, saponins, steroids, gums & mucilages and carbohydrate. Both native and commercial carrageenans exhibited better antioxidant activities such as total antioxidant capacity (87±0.47 and 82.6±0.47μg A.A/g), hydroxyl radical scavenging activity (61.4±0.27 and 58.66±0.31μg/ml), nitric oxide radical scavenging activity (80.42±0.22 and 73.66±0.22μg/ml), DPPH radical scavenging activity (56.26±0.20 and 53.67±0.082μg/ml) and reducing power assay (46.57±0.32 and 42.54±0.27μg/ml) at the maximum concentration of 100μg/ml carrageenans. These results indicated that native carrageenan from K. alvarezii possessed better antioxidant potential in comparison with commercial carrageenan. Anticancer activities of both carrageenans showed excellent inhibition on the growth of breast, colon, liver and osteosarcoma cell lines at the maximum concentration of 150μg/ml. Native carrageenan exhibited an excellent anticancer activity on colon carcinoma cell lines (67.66±0.168%) with the IC 50 value of 73.87μg/ml and commercial carrageenan possessed a potent inhibition on the growth of breast cancer cell lines (67.33±0.077%) with the IC 50 value of 123.8μg/ml. These results clearly indicated the beneficial effect of native and commercial carrageenans as anticancer agents being a free radical scavenger. Anti-diabetic property of both carrageenans showed inhibition effect on α- glucosidase enzyme. The inhibitory effect depends on concentration of carrageenans and it was recorded that maximum (74.49±1.05 and 67.42±0.63) inhibitory effect of α- glucosidase enzyme at 500μg/ml concentration. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Antidiabetic effects of flavonoids from Sophora flavescens EtOAc extract in type 2 diabetic KK-ay mice.

PubMed

Yang, Xinzhou; Yang, Jing; Xu, Chan; Huang, Mi; Zhou, Qi; Lv, Jingnan; Ma, Xinhua; Ke, Changqiang; Ye, Yang; Shu, Guangwen; Zhao, Ping

2015-08-02

Bitter and cold Chinese medicines have been long used for the treatment for diabetes mellitus (DM) for thousands of years in China. The roots of Sophora flavescens Ait., one of bitter and cold Chinese medicines commonly used to remove lung heat have been used to counteract DM and exerted good clinical effects for diabetic patients in some folk hospitals in Fujian province, PR China. However, the corresponding active principles and antidiabetic mechanism of this Traditional Chinese Medicine remain unclear. Therefore, in this study, we aim at chemical profiling of the active principles, validating the potential antidiabetic effects of the active EtOAc extract (SF-EtOAc) in vitro and in vivo, and elucidating its probable antidiabetic mechanism as well as evaluating its acute oral toxicity. An off-line semi-preparative LC-NMR and LC-UV-ESI MS protocol was developed to determine the chemical principles of the active EtOAc extract rapidly and unambiguously. The effect of SF-EtOAc on the glucose transporter type 4 (GLUT4) translocation in L6 myotubes was examined. T2DM KK-Ay mice were induced by high-fat diet. SF-EtOAc was orally administration at the dose of 30, 60 and 120 mg/kg/d, for 21 days. Metformin was used as positive control. Body weight, plasma glucose, oral glucose tolerance test, serum insulin and blood-lipid indexes were measured. Phosphorylation of the AMP-activated protein kinase (AMPK) expression in liver was measured. We found that SF-EtOAc significantly improved oral glucose tolerance, increased serum high density lipoprotein cholesterol (HDL-C) and reduced body weight, blood glucose levels and other related blood-lipid indexes. Mechanistically, SF-EtOAc elevated phosphorylation of AMP-activated protein kinase (AMPK) and stimulated membrane translocation of GLUT4. Moreover, it was unveiled that oral median lethal dose (LD50) of SF-EtOAc was more than 7500 mg/kg, suggesting that SF-EtOAc was practically non-toxic for mice. SF-EtOAc improves glucose tolerance, reduces hyperglycemia and resumes insulin levels, at least in part, by activating GLUT4 translocation which may be modulated by AMPK pathway. According to the results of the present study, SF-EtOAc possesses a potent antidiabetic activity and could be used as a safe remedy for the treatment of diabetes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Strategies for prevention of hyperglycaemic emergencies in Nigeria.

PubMed

Balogun, Wo; Adeleye, Jo

2008-12-01

The mortality and morbidity of acute metabolic complications of diabetes, particularly DKA and HHS are unacceptably high in Nigeria. Prevention of occurrence of these hyperglycaemic emergencies (HE) is the only rational way for a resource poor country like Nigeria. Prevention requires careful identification of precipitating factors of HE. The leading precipitating factors of HE in Nigeria are infections, inadequate or inappropriate use of anti-diabetic agents, especially insulin. HE may also be the first presentation in persons previously unknown to have diabetes. Measures to prevent HE include creation of awareness in the public, effective and systematic education of the persons living with diabetes and capacity building and manpower development of the healthcare personnel. There should be critical appraisal of our healthcare system with a view to restructuring so it can be more accessible to patients and can deliver quality diabetes care. Finally government must sincerely provide an alternative of healthcare financing for the citizens, especially those living with chronic medical conditions like diabetes.

STRATEGIES FOR PREVENTION OF HYPERGLYCAEMIC EMERGENCIES IN NIGERIA

PubMed Central

Balogun, WO; Adeleye, JO

2008-01-01

The mortality and morbidity of acute metabolic complications of diabetes, particularly DKA and HHS are unacceptably high in Nigeria. Prevention of occurrence of these hyperglycaemic emergencies (HE) is the only rational way for a resource poor country like Nigeria. Prevention requires careful identification of precipitating factors of HE. The leading precipitating factors of HE in Nigeria are infections, inadequate or inappropriate use of anti-diabetic agents, especially insulin. HE may also be the first presentation in persons previously unknown to have diabetes. Measures to prevent HE include creation of awareness in the public, effective and systematic education of the persons living with diabetes and capacity building and manpower development of the healthcare personnel. There should be critical appraisal of our healthcare system with a view to restructuring so it can be more accessible to patients and can deliver quality diabetes care. Finally government must sincerely provide an alternative of healthcare financing for the citizens, especially those living with chronic medical conditions like diabetes. PMID:25161450

α-Glucosidase and tyrosinase inhibitory effects of an abietane type diterpenoid taxoquinone from Metasequoia glyptostroboides.

PubMed

Bajpai, Vivek K; Park, Yong-Ha; Na, MinKyun; Kang, Sun Chul

2015-03-26

Nowadays plant derived natural compounds have gained huge amount of research attention especially in food and medicine industries due to their multitude of biological and therapeutic properties as alternative medicines. In this study, a diterpenoid compound taxoquinone, isolated from Metasequoia glyptostroboides was evaluated for its α-glucosidase and tyrosinase inhibitory efficacy in terms of its potent anti-diabetic and depigmentation potential, respectively. As a result, taxoquinone at the concentration range of 100-3,000 μg/mL and 200-1,000 μg/mL showed potent efficacy on inhibiting α-glucosidase and tyrosinase enzymes by 9.24-51.32% and 11.14-52.32%, respectively. The findings of this study clearly evident potent therapeutic efficacy of an abietane diterpenoid taxoquinone isolated from M. glyptostroboides with a possibility for using it as a novel candidate in food and medicine industry as a natural alternative medicine to prevent diabetes mellitus type-2 related disorders and as a depigmentation agent.

(S)-[6]-Gingerol enhances glucose uptake in L6 myotubes by activation of AMPK in response to [Ca2+]i.

PubMed

Li, Yiming; Tran, Van H; Koolaji, Nooshin; Duke, Colin; Roufogalis, Basil D

2013-01-01

The aim of this study was to investigate the mechanism of (S)-[6]-gingerol in promoting glucose uptake in L6 skeletal muscle cells. The effect of (S)-[6]-gingerol on glucose uptake in L6 myotubes was examined using 2-[1,2-3H]-deoxy-D-glucose. Intracellular Ca2+ concentration was measured using Fluo-4. Phosphorylation of AMPKα was determined by Western blotting analysis. (S)-[6]-Gingerol time-dependently enhanced glucose uptake in L6 myotubes. (S)-[6]-Gingerol elevated intracellular Ca2+ concentration and subsequently induced a dose- and time-dependent enhancement of threonine172 phosphorylated AMPKα in L6 myotubes via modulation by Ca2+/calmodulin-dependent protein kinase kinase. The results indicated that (S)-[6]-gingerol increased glucose uptake in L6 skeletal muscle cells by activating AMPK. (S)-[6]-gingerol, a major component of Zingiber officinale, may have potential for development as an antidiabetic agent.

Evidence of Immunosuppressive and Th2 Immune Polarizing Effects of Antidiabetic Momordica charantia Fruit Juice.

PubMed

Fachinan, Rufine; Fagninou, Adnette; Nekoua, Magloire Pandoua; Amoussa, Abdou Madjid; Adjagba, Marius; Lagnika, Latifou; Lalèyè, Anatole; Moutairou, Kabirou; Yessoufou, Akadiri

2017-01-01

The mechanism of action of the antidiabetic capacity of Momordica charantia is still under investigation. Here, we assessed phytochemical compositions, antioxidant activity, and effects of total and filtered fruit and leafy stem juices of Momordica charantia on human T cell proliferation and differentiation through quantification of Th1/Th2 cytokines. In the absence of stimulation, total fruit and leafy stem juices induced significant T cell proliferation. Under PHA stimulation, both juices potentiated plant-induced T cell proliferation. However, the filtered fruit and leafy stem juices significantly inhibited PHA-stimulated T cell proliferation, while neither juice influenced T cell proliferation. Moreover, total and filtered fruit juice increased IL-4 secretion, while total and filtered leafy stem juice enhanced IFN- γ production. Phytochemical screening revealed the presence of tannins, flavonoids, anthocyans, steroids, and triterpenoids in both juices. Alkaloids, quinone derivatives, cardenolides, and cyanogenic derivatives were undetectable. The saponins present in total juices were undetectable after filtration. Moreover, both juices had appreciable antioxidant capacity. Our study supports the type 1 antidiabetic effect of filtered fruit juice of M. charantia which may be related to its immunosuppressive and T-helper 2 cell inducing capacities. Due to their immune-stimulatory activities and their ability to increase T-helper 1 cell cytokines, total fruit and leafy stem juices may serve in the treatment of immunodeficiency and certain infections.

Evidence of Immunosuppressive and Th2 Immune Polarizing Effects of Antidiabetic Momordica charantia Fruit Juice

PubMed Central

Amoussa, Abdou Madjid; Adjagba, Marius; Lagnika, Latifou; Lalèyè, Anatole

2017-01-01

The mechanism of action of the antidiabetic capacity of Momordica charantia is still under investigation. Here, we assessed phytochemical compositions, antioxidant activity, and effects of total and filtered fruit and leafy stem juices of Momordica charantia on human T cell proliferation and differentiation through quantification of Th1/Th2 cytokines. In the absence of stimulation, total fruit and leafy stem juices induced significant T cell proliferation. Under PHA stimulation, both juices potentiated plant-induced T cell proliferation. However, the filtered fruit and leafy stem juices significantly inhibited PHA-stimulated T cell proliferation, while neither juice influenced T cell proliferation. Moreover, total and filtered fruit juice increased IL-4 secretion, while total and filtered leafy stem juice enhanced IFN-γ production. Phytochemical screening revealed the presence of tannins, flavonoids, anthocyans, steroids, and triterpenoids in both juices. Alkaloids, quinone derivatives, cardenolides, and cyanogenic derivatives were undetectable. The saponins present in total juices were undetectable after filtration. Moreover, both juices had appreciable antioxidant capacity. Our study supports the type 1 antidiabetic effect of filtered fruit juice of M. charantia which may be related to its immunosuppressive and T-helper 2 cell inducing capacities. Due to their immune-stimulatory activities and their ability to increase T-helper 1 cell cytokines, total fruit and leafy stem juices may serve in the treatment of immunodeficiency and certain infections. PMID:28812026

Antidiabetic and renoprotective effects of Cladophora glomerata Kützing extract in experimental type 2 diabetic rats: a potential nutraceutical product for diabetic nephropathy.

PubMed

Srimaroeng, Chutima; Ontawong, Atcharaporn; Saowakon, Naruwan; Vivithanaporn, Pornpun; Pongchaidecha, Anchalee; Amornlerdpison, Doungporn; Soodvilai, Sunhapas; Chatsudthipong, Varanuj

2015-01-01

Cladophora glomerata extract (CGE) has been shown to exhibit antigastric ulcer, anti-inflammatory, analgesic, hypotensive, and antioxidant activities. The present study investigated antidiabetic and renoprotective effects of CGE in type 2 diabetes mellitus (T2DM) rats. The rats were induced by high-fat diet and streptozotocin and supplemented daily with 1 g/kg BW of CGE for 12 weeks. The renal transport function was assessed by the uptake of para-aminohippurate mediated organic anion transporters 1 (Oat1) and 3 (Oat3), using renal cortical slices. These two transporters were known to be upregulated by insulin and PKCζ while they were downregulated by PKCα activation. Compared to T2DM, CGE supplemented rats had significantly improved hyperglycaemia, hypertriglyceridemia, insulin resistance, and renal morphology. The baseline uptake of para-aminohippurate was not different among experimental groups and was correlated with Oat1 and 3 mRNA expressions. Nevertheless, while insulin-stimulated Oat1 and 3 functions in renal slices were blunted in T2DM rats, they were improved by CGE supplementation. The mechanism of CGE-restored insulin-stimulated Oat1 and 3 functions was clearly shown to be associated with upregulated PKCζ and downregulated PKCα expressions and activations. These findings indicate that CGE has antidiabetic effect and suggest it may prevent diabetic nephropathy through PKCs in a T2DM rat model.

Marine Organisms with Anti-Diabetes Properties

PubMed Central

Lauritano, Chiara; Ianora, Adrianna

2016-01-01

Diabetes is a chronic degenerative metabolic disease with high morbidity and mortality rates caused by its complications. In recent years, there has been a growing interest in looking for new bioactive compounds to treat this disease, including metabolites of marine origin. Several aquatic organisms have been screened to evaluate their possible anti-diabetes activities, such as bacteria, microalgae, macroalgae, seagrasses, sponges, corals, sea anemones, fish, salmon skin, a shark fusion protein as well as fish and shellfish wastes. Both in vitro and in vivo screenings have been used to test anti-hyperglycemic and anti-diabetic activities of marine organisms. This review summarizes recent discoveries in anti-diabetes properties of several marine organisms as well as marine wastes, existing patents and possible future research directions in this field. PMID:27916864

Glycaemic control and antidiabetic treatment trends in primary care centres in patients with type 2 diabetes mellitus during 2007–2013 in Catalonia: a population-based study

PubMed Central

Mata-Cases, Manel; Franch-Nadal, Josep; Real, Jordi; Mauricio, Dídac

2016-01-01

Objectives To assess trends in prescribing practices of antidiabetic agents and glycaemic control in patients with type 2 diabetes mellitus (T2DM). Design Cross-sectional analysis using yearly clinical data and antidiabetic treatments prescribed obtained from an electronic population database. Setting Primary healthcare centres, including the entire population attended by the Institut Català de la Salut in Catalonia, Spain, from 2007 to 2013. Participants Patients aged 31–90 years with a diagnosis of T2DM. Results The number of registered patients with T2DM in the database was 257 072 in 2007, increasing up to 343 969 in 2013. The proportion of patients not pharmacologically treated decreased by 9.7% (95% CI −9.48% to −9.92%), while there was an increase in the percentage of patients on monotherapy (4.4% increase; 95% CI 4.16% to 4.64%), combination therapy (2.8% increase; 95% CI 2.58% to 3.02%), and insulin alone or in combination (increasing 2.5%; 95% CI 2.2% to 2.8%). The use of metformin and dipeptidyl peptidase-IV inhibitors increased gradually, while sulfonylureas, glitazones and α-glucosidase inhibitors decreased. The use of glinides remained stable, and the use of glucagon-like peptide-1 receptor agonists was still marginal. Regarding glycaemic control, there were no relevant differences across years: mean glycated haemoglobin (HbA1c) value was around 7.2%; the percentage of patients reaching an HbA1c≤7% target ranged between 52.2% and 55.6%; and those attaining their individualised target from 72.8% to 75.7%. Conclusions Although the proportion of patients under pharmacological treatment increased substantially over time and there was an increase in the use of combination therapies, there have not been relevant changes in glycaemic control during the 2007–2013 period in Catalonia. PMID:27707830

An open-label drug-drug interaction study of the steady-state pharmacokinetics of topiramate and glyburide in patients with type 2 diabetes mellitus.

PubMed

Manitpisitkul, Prasarn; Curtin, Christopher R; Shalayda, Kevin; Wang, Shean-Sheng; Ford, Lisa; Heald, Donald L

2013-12-01

Topiramate is approved for epilepsy and migraine headache management and has potential antidiabetic activity. Because topiramate and antidiabetic drugs may be co-administered, the potential drug-drug interactions between topiramate and glyburide (glibenclamide), a commonly used sulfonylurea antidiabetic agent, was evaluated at steady state in patients with type 2 diabetes mellitus (T2DM). This was a single-center, open-label, phase I, drug interaction study of topiramate (150 mg/day) and glyburide (5 mg/day alone and concomitantly) in patients with T2DM. The study consisted of 14-day screening, 48-day open-label treatment, and a 7-day follow-up phase. Serial blood and urine were obtained and analyzed by liquid chromatography coupled mass spectrometry/mass spectrometry for topiramate, glyburide, and its active metabolites M1 (4-trans-hydroxy-glyburide) and M2 (3-cis-hydroxy-glyburide) concentrations. Pharmacokinetic parameters were estimated by model-independent methods. Changes in fasting plasma glucose from baseline and safety parameters were monitored throughout the study. Of 28 enrolled patients, 24 completed the study. Co-administration of topiramate resulted in a significant (p < 0.05) decrease in the glyburide area under the concentration-time curve (25 %) and maximum plasma concentration (22 %), and reduction in systemic exposure of M1 (13 %) and M2 (15 %). Renal clearance of M1 (13 %) and M2 (12 %) increased during treatment with topiramate. Steady-state pharmacokinetics of topiramate were unaffected by co-administration of glyburide. Co-administration of topiramate and glyburide was generally tolerable in patients with T2DM. Glyburide did not affect the pharmacokinetics of topiramate. Co-administration of topiramate decreased systemic exposure of glyburide and its active metabolites; combined treatment may require dosing adjustments of glyburide as per clinical judgment and glycemic control.

mTOR and Cardiovascular Diseases: Diabetes Mellitus.

PubMed

Vergès, Bruno

2018-02-01

The mammalian targets of rapamycin (mTOR) inhibitors are potent immunosuppressors used for prevention of acute rejection after transplantation and have been more recently used as anticancer drugs. mTOR inhibitors have a significant impact on glucose metabolism and frequently induce diabetes. mTOR inhibitors, when used as immunosuppressive agents (sirolimus, everolimus), can induce diabetes with an incidence which is low when used without calcineurin inhibitors but high when used in combination with calcineurin inhibitors (from 11.0% to 38.1%). mTOR inhibitors used as anticancer agents (everolimus, temsirolimus) increase significantly the risk for new-onset diabetes and induce a 5-fold increase in the risk for severe hyperglycemia. The deleterious effect of mTOR inhibitors on glucose metabolism is due to an increased insulin resistance secondary to a reduction of the insulin signaling pathway within the cell and a reduction of insulin secretion via a direct effect on the pancreatic beta cells. Because of the risk for diabetes, it is recommended, when starting a treatment with an mTOR inhibitor, to check fasting blood glucose every 2 weeks during the first month of treatment then every month and HbA1c every 3 months and to intensify self-monitoring of blood glucose in patients with known diabetes. When fasting blood glucose is more than 126 mg/dL (7.0 mmol/L), when plasma glucose is more than 200 mg/dL at any time, or when HbA1c is more than 6.5%, it is recommended to start antidiabetic treatment.

Cognitive remission: a novel objective for the treatment of major depression?

PubMed

Bortolato, Beatrice; Miskowiak, Kamilla W; Köhler, Cristiano A; Maes, Michael; Fernandes, Brisa S; Berk, Michael; Carvalho, André F

2016-01-22

Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD. Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD.

α-Glucosidase inhibitory effect of resveratrol and piceatannol.

PubMed

Zhang, Albert J; Rimando, Agnes M; Mizuno, Cassia S; Mathews, Suresh T

2017-09-01

Dietary polyphenols have been shown to inhibit α-glucosidase, an enzyme target of some antidiabetic drugs. Resveratrol, a polyphenol found in grapes and wine, has been reported to inhibit the activity of yeast α-glucosidase. This triggered our interest to synthesize analogs and determine their effect on mammalian α-glucosidase activity. Using either sucrose or maltose as substrate resveratrol, piceatannol and 3'-hydroxypterostilbene showed strong inhibition of mammalian α-glucosidase activity; pinostilbene, cis-desoxyrhapontigenin and trans-desoxyrhapontigenin had moderate inhibition. Compared to acarbose (IC 50 3-13 μg/ml), piceatannol and resveratrol inhibited mammalian α-glucosidase to a lesser extent (IC 50 14-84 and 111-120 μg/ml, respectively). 3'-Hydroxypterostilbene (IC 50 105-302 μg/ml) was 23-35-fold less potent than acarbose. We investigated the effect of piceatannol and resveratrol on postprandial blood glucose response in high-fat-fed C57Bl/6 mice. Animals administered resveratrol (30 mg/kg body weight [BW]) or piceatannol (14 mg/kg BW) 60 min prior to sucrose or starch loading had a delayed absorption of carbohydrates, resulting in significant lowering of postprandial blood glucose concentrations, similar to the antidiabetic drug acarbose, while no significant effect was observed with the glucose-loaded animals. Our studies demonstrate that the dietary polyphenols resveratrol and piceatannol lower postprandial hyperglycemia and indicate that inhibition of intestinal α-glucosidase activity may be a potential mechanism contributing to their antidiabetic property. Copyright © 2017 Elsevier Inc. All rights reserved.

A novel Gymnema sylvestre extract stimulates insulin secretion from human islets in vivo and in vitro.

PubMed

Al-Romaiyan, A; Liu, B; Asare-Anane, H; Maity, C R; Chatterjee, S K; Koley, N; Biswas, T; Chatterji, A K; Huang, G-C; Amiel, S A; Persaud, S J; Jones, P M

2010-09-01

Many plant-based products have been suggested as potential antidiabetic agents, but few have been shown to be effective in treating the symptoms of Type 2 diabetes mellitus (T2DM) in human studies, and little is known of their mechanisms of action. Extracts of Gymnema sylvestre (GS) have been used for the treatment of T2DM in India for centuries. The effects of a novel high molecular weight GS extract, Om Santal Adivasi, (OSA(R)) on plasma insulin, C-peptide and glucose in a small cohort of patients with T2DM are reported here. Oral administration of OSA(R) (1 g/day, 60 days) induced significant increases in circulating insulin and C-peptide, which were associated with significant reductions in fasting and post-prandial blood glucose. In vitro measurements using isolated human islets of Langerhans demonstrated direct stimulatory effects of OSA(R) on insulin secretion from human ß-cells, consistent with an in vivo mode of action through enhancing insulin secretion. These in vivo and in vitro observations suggest that OSA(R) may provide a potential alternative therapy for the hyperglycemia associated with T2DM. Copyright 2010 John Wiley & Sons, Ltd.

Enhanced Incretin Effects of Exendin-4 Expressing Chimeric Plasmid Based On Two-Step Transcription Amplification System with Dendritic Bioreducible Polymer for the Treatment of Type 2 Diabetes

PubMed Central

Kim, Pyung-Hwan; Lee, Minhyung; Nam, Kihoon; Kim, Sung Wan

2014-01-01

Glucagon-like peptide 1 (GLP-1) agonist, exenxdin-4, is currently being advanced as a promising diabetes remedy via a variety of incretin actions similar with GLP-1. In this study, we investigated an effective anti-diabetic therapy via exendin-4 expressing chimeric plasmid based on two-step transcription amplification (TSTA) system with dendrimer-type bioreducible polymer for more improved incretin-based gene therapy. Arginine-grafted poly (cystaminebisacrylamide-diaminohexane) (ABP)-conjugated poly (amido amine) (PAMAM) dendrimer (PAM-ABP) was used as gene carrier. PAM-ABP/chimeric DNA polyplex was markedly elevated exendin-4 expression in ectopic cells as well as increased insulin production through an enhanced activation of protein kinase K (PKA) induced by up-regulation of exendin-4-stimulated cyclic adenosine monophosphate (cAMP) in pancreatic β-cell. Consistent with these results, intravenous administration of PAM-ABP/chimeric DNA polyplex improved glucoregulotory effects, as well as increased insulin secretion by high expression of exendin-4 in blood in type 2 diabetic mice with no any toxicity. Our exendin-4 system can be attributed to provide a potential diabetes therapeutic agent for improved incretin gene therapy. PMID:24839613

Molecular Mechanisms Underlying the Cardiovascular Benefits of SGLT2i and GLP-1RA.

PubMed

Khat, Dorrin Zarrin; Husain, Mansoor

2018-06-09

In addition to their effects on glycemic control, two specific classes of relatively new anti-diabetic drugs, namely the sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated reduced rates of major adverse cardiovascular events (MACE) in subjects with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). This review summarizes recent experimental results that inform putative molecular mechanisms underlying these benefits. SGLT2i and GLP-1RA exert cardiovascular effects by targeting in both common and distinctive ways (A) several mediators of macro- and microvascular pathophysiology: namely (A1) inflammation and atherogenesis, (A2) oxidative stress-induced endothelial dysfunction, (A3) vascular smooth muscle cell reactive oxygen species (ROS) production and proliferation, and (A4) thrombosis. These agents also exhibit (B) hemodynamic effects through modulation of (B1) natriuresis/diuresis and (B2) the renin-angiotensin-aldosterone system. This review highlights that while GLP-1RA exert direct effects on vascular (endothelial and smooth muscle) cells, the effects of SGLT2i appear to include the activation of signaling pathways that prevent adverse vascular remodeling. Both SGLT2i and GLP-1RA confer hemodynamic effects that counter adverse cardiac remodeling.

Glycogen synthase kinase 3: more than a namesake

PubMed Central

Rayasam, Geetha Vani; Tulasi, Vamshi Krishna; Sodhi, Reena; Davis, Joseph Alex; Ray, Abhijit

2009-01-01

Glycogen synthase kinase 3 (GSK3), a constitutively acting multi-functional serine threonine kinase is involved in diverse physiological pathways ranging from metabolism, cell cycle, gene expression, development and oncogenesis to neuroprotection. These diverse multiple functions attributed to GSK3 can be explained by variety of substrates like glycogen synthase, τ protein and β catenin that are phosphorylated leading to their inactivation. GSK3 has been implicated in various diseases such as diabetes, inflammation, cancer, Alzheimer's and bipolar disorder. GSK3 negatively regulates insulin-mediated glycogen synthesis and glucose homeostasis, and increased expression and activity of GSK3 has been reported in type II diabetics and obese animal models. Consequently, inhibitors of GSK3 have been demonstrated to have anti-diabetic effects in vitro and in animal models. However, inhibition of GSK3 poses a challenge as achieving selectivity of an over achieving kinase involved in various pathways with multiple substrates may lead to side effects and toxicity. The primary concern is developing inhibitors of GSK3 that are anti-diabetic but do not lead to up-regulation of oncogenes. The focus of this review is the recent advances and the challenges surrounding GSK3 as an anti-diabetic therapeutic target. British Journal of Pharmacology (2009) doi:10.1111/j.1476-5381.2008.00085.x PMID:19366350

Inhibitory activities of the alkaloids from Coptidis Rhizoma against aldose reductase.

PubMed

Jung, Hyun Ah; Yoon, Na Young; Bae, Hyun Ju; Min, Byung-Sun; Choi, Jae Sue

2008-11-01

As part of our ongoing search of natural sources for therapeutic and preventive agents for diabetic complications, the rat lens aldose reductase (RLAR) inhibitory effect of Coptidis Rhizoma (the rhizome of Coptis chinensis Franch) was evaluated. Its extract and fractions exhibited broad and moderate RLAR inhibitory activities of 38.9 approximately 67.5 microg/mL. In an attempt to identify bioactive components, six quaternary protoberberine-type alkaloids (berberine, palmatine, jateorrhizine, epiberberine, coptisine, and groenlandicine) and one quaternary aporphine-type alkaloid (magnoflorine) were isolated from the most active n-BuOH fraction, and the chemical structures therein were elucidated on the basis of spectroscopic evidence and comparison with published data. The anti-diabetic complications capacities of seven C. chinensis-derived alkaloids were evaluated via RLAR and human recombinant AR (HRAR) inhibitory assays. Although berberine and palmatine were previously reported as prime contributors to AR inhibition, these two major components exhibited no AR inhibitory effects at a higher concentration of 50 microg/ml in the present study. Conversely, epiberberine, coptisine, and groenlandicine exhibited moderate inhibitory effects with IC(50) values of 100.1, 118.4, 140.1 microM for RLAR and 168.1, 187.3, 154.2 microM for HRAR. The results clearly indicated that the presence of the dioxymethylene group in the D ring and the oxidized form of the dioxymethylene group in the A ring were partly responsible for the AR inhibitory activities of protoberberine-type alkaloids. Therefore, Coptidis Rhizoma, and the alkaloids contained therein, would clearly have beneficial uses in the development of therapeutic and preventive agents for diabetic complications and diabetes mellitus.

Functional food red yeast rice (RYR) for metabolic syndrome amelioration: a review on pros and cons.

PubMed

Patel, Seema

2016-05-01

Red yeast rice (RYR), the fermentation product of mold Monascus purpureus has been an integral part of Oriental food and traditional Chinese medicine, long before the discovery of their medicinal roles. With the identification of bioactive components as polyketide pigments (statins), and unsaturated fatty acids, RYR has gained a nutraceutical status. Hypercholesterolemic effect of this fermented compound has been validated and monacolin K has been recognized as the pivotal component in cholesterol alleviation. Functional similarity with commercial drug lovastatin sans the side effects has catapulted its popularity in other parts of the world as well. Apart from the hypotensive role, ameliorative benefits of RYR as anti-inflammatory, antidiabetic, anticancer and osteogenic agent have emerged, fueling intense research on it. Mechanistic studies have revealed their interaction with functional agents like coenzyme Q10, astaxanthin, vitamin D, folic acid, policosanol, and berberine. On the other hand, concurrence of mycotoxin citrinin and variable content of statin has marred its integration in mainstream medication. In this disputable scenario, evaluation of the scopes and lacunae to overcome seems to contribute to an eminent area of healthcare. Red yeast rice (RYR), the rice-based fermentation product of mold Monascus purpureus is a functional food. Its bioactive component monacolin K acts like synthetic drug lovastatin, without the severe side effects of the latter. RYR has been validated to lower cholesterol, control high blood pressure; confer anti-flammation, hypoglycaemic, anticancer and osteogenic properties. However, dose inconsistency and co-occurrence of toxin citrinin hampers its dietary supplementation prospect. Further research might facilitate development of RYR as a nutraceutical.

Antiobesity Pharmacotherapy for Patients with Type 2 Diabetes: Focus on Long-Term Management

PubMed Central

Jeon, Won Seon

2014-01-01

Type 2 diabetes and obesity have a complex relationship; obesity is linked to insulin resistance, the precursor to type 2 diabetes. The management of obesity is an important method to delay onset of diabetes and improve the glycemic durability of antidiabetic agents. However, insulin and some of the oral hypoglycemic agents used to treat diabetes cause significant weight gain, and it is difficult for patients with diabetes to reduce and maintain their weight by life-style changes alone. Thus, antiobesity medications or bariatric surgery may be a necessary adjunct for certain obese patients with diabetes. In 2012, the U.S. Food and Drug Administration (FDA) approved lorcaserin and phentermine/topiramate extended-release for the management of chronic weight, and approval for naltrexone/bupropion sustained-release as an adjunct to exercise and reduced caloric intake followed in 2014. Liraglutide is pending FDA approval for antiobesity drug. Here we review the efficacy of approved and new promising drugs for the management of obesity. PMID:25559569

Synthesis, characterization, bioactivity and potential application of phenolic acid grafted chitosan: A review.

PubMed

Liu, Jun; Pu, Huimin; Liu, Shuang; Kan, Juan; Jin, Changhai

2017-10-15

In recent years, increasing attention has been paid to the grafting of phenolic acid onto chitosan in order to enhance the bioactivity and widen the application of chitosan. Here, we present a comprehensive overview on the recent advances of phenolic acid grafted chitosan (phenolic acid-g-chitosan) in many aspects, including the synthetic method, structural characterization, biological activity, physicochemical property and potential application. In general, four kinds of techniques including carbodiimide based coupling, enzyme catalyzed grafting, free radical mediated grafting and electrochemical methods are frequently used for the synthesis of phenolic acid-g-chitosan. The structural characterization of phenolic acid-g-chitosan can be determined by several instrumental methods. The physicochemical properties of chitosan are greatly altered after grafting. As compared with chitosan, phenolic acid-g-chitosan exhibits enhanced antioxidant, antimicrobial, antitumor, anti-allergic, anti-inflammatory, anti-diabetic and acetylcholinesterase inhibitory activities. Notably, phenolic acid-g-chitosan shows potential applications in many fields as coating agent, packing material, encapsulation agent and bioadsorbent. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antidiabetic activities of aqueous and ethanolic extracts of Piper betle leaves in rats.

PubMed

Arambewela, L S R; Arawwawala, L D A M; Ratnasooriya, W D

2005-11-14

Leaves of Piper betle (Piperaceae) possess several bioactivities and are used in traditional medicinal systems. However, its antidiabetic activity has not been scientifically investigated so far. The aim of this study therefore, was to investigate the antidiabetic activity of Piper betle leaves. This was tested in normoglycaemic and strepozotocin (STZ)-induced diabetic rats using oral administration of hot water extract (HWE) and cold ethanolic extract (CEE). In normoglycaemic rats, both HWE and CEE significantly lowered the blood glucose level in a dose-dependent manner. In glucose tolerance test, both extracts markedly reduced the external glucose load. The antidiabetic activity of HWE is comparable to that of CEE. Moreover, HWE failed to inhibit the glucose absorption from the small intestine of rats. Both extracts were found to be non-toxic and well tolerated after following chronic oral administration (no overt signs of toxicity, hepatotoxicity or renotoxicity). However, the weight of the spleen had increased in treated groups possibly indicating lymphoproliferative activity. It is concluded that HWE and CEE of Piper betle leaves possess safe and strong antidiabetic activity.

Something old, something new and something very old: drugs for treating type 2 diabetes.

PubMed

Kaiser, D; Oetjen, E

2014-06-01

Diabetes mellitus belongs to the most rapidly increasing diseases worldwide. Approximately 90-95% of these patients suffer from type 2 diabetes mellitus, which is characterized by peripheral insulin resistance and the progressive loss of beta-cell function and mass. Considering the complications of this chronic disease, a reliable anti-diabetic treatment is indispensable. An ideal oral anti-diabetic drug should not only correct glucose homeostasis but also preserve or even augment beta-cell function and mass, ameliorate the subclinical inflammation present under insulin-resistant conditions and prevent the macro- and microvascular consequences of diabetes in order to reduce the mortality. Despite the many anti-diabetic drugs already in use, there is an ongoing research for additional drugs, guided by different concepts of the pathogenesis of type 2 diabetes. This review will briefly summarize current oral anti-diabetic drugs. In addition, emerging strategies for the treatment of diabetes will be described, among them the inhibition of glucagon action and anti-inflammatory drugs. Their suitability as 'ideal anti-diabetic drugs' will be discussed. © 2014 The British Pharmacological Society.

Pistacia lentiscus Oleoresin: Virtual Screening and Identification of Masticadienonic and Isomasticadienonic Acids as Inhibitors of 11β-Hydroxysteroid Dehydrogenase 1.

PubMed

Vuorinen, Anna; Seibert, Julia; Papageorgiou, Vassilios P; Rollinger, Judith M; Odermatt, Alex; Schuster, Daniela; Assimopoulou, Andreana N

2015-04-01

In traditional medicine, the oleoresinous gum of Pistacia lentiscus var. chia, so-called mastic gum, has been used to treat multiple conditions such as coughs, sore throats, eczema, dyslipidemia, and diabetes. Mastic gum is rich in triterpenes, which have been postulated to exert antidiabetic effects and improve lipid metabolism. In fact, there is evidence of oleanonic acid, a constituent of mastic gum, acting as a peroxisome proliferator-activated receptor γ agonist, and mastic gum being antidiabetic in mice in vivo. Despite these findings, the exact antidiabetic mechanism of mastic gum remains unknown. Glucocorticoids play a key role in regulating glucose and fatty acid metabolism, and inhibition of 11β-hydroxysteroid dehydrogenase 1 that converts inactive cortisone to active cortisol has been proposed as a promising approach to combat metabolic disturbances including diabetes. In this study, a pharmacophore-based virtual screening was applied to filter a natural product database for possible 11β-hydroxysteroid dehydrogenase 1 inhibitors. The hit list analysis was especially focused on the triterpenoids present in Pistacia species. Multiple triterpenoids, such as masticadienonic acid and isomasticadienonic acid, main constituents of mastic gum, were identified. Indeed, masticadienonic acid and isomasticadienonic acid selectively inhibited 11β-hydroxysteroid dehydrogenase 1 over 11β-hydroxysteroid dehydrogenase 2 at low micromolar concentrations. These findings suggest that inhibition of 11β-hydroxysteroid dehydrogenase 1 contributes to the antidiabetic activity of mastic gum. Georg Thieme Verlag KG Stuttgart · New York.

Antidiabetic and Antioxidant Activity of Scoparia dulcis Linn.

PubMed Central

Mishra, M. R.; Mishra, A.; Pradhan, D. K.; Panda, A. K.; Behera, R. K.; Jha, S.

2013-01-01

The hypoglycaemic activity of methanol extract of Scoparia dulcis was performed on both in vitro and in vivo models along with determination of total extractable polyphenol. Methanol extract of Scoparia dulcis contains 4.9% and water extract contains 3.2% of total extractable polyphenol. The antioxidant activity showed very promising result in both the tested methods that is 2,2-diphenyl-1-picrylhydrazyl and ferric ion reducing capacity. The antioxidant activity is directly correlated to the antidiabetic potential of drug. The two enzymes (amylase and glycosidase) found in intestine are responsible for the increasing postprandial glucose in body. In vitro model was performed on these enzymes and the results showed that methanol extract of Scoparia dulcis was effective to check the postprandial glucose level. The in vivo hypoglycaemic activity of methanol extract of Scoparia dulcis was performed on streptozotocin-induced diabetes mellitus showed significant inhibition of blood glucose level as compared to control and similar to that of standard glibenclamide. The overall data potentiates the traditional value of Scoparia dulcis as an antidiabetic drug. PMID:24403665

Antidiabetics and diuretics show phototoxicity in HaCaT cells

NASA Astrophysics Data System (ADS)

Selvaag, Edgar; Petersen, Anita B.; Gniadecki, Robert; Thorn, Tine; Wulf, Hans Christian

2001-10-01

The antidiabetics tolbutamide, glibenclamide, and glipizide, and the diuretics bendroflumethiazide, butizide, furosemide, hydrochlorothiazide, and trichlormethiazide were investigated for potential phototoxicity in the HaCaT cell line. The cells were incubated with the drugs and then exposed to UVA1 irradiation. The effects of the antioxidants L-ascorbic acid, and (alpha) -tocopherol on oxidative DNA damage were assessed. Bendroflumethiazide, furosemide, hydrochlorothiazide, trichlormethiazide, or tolbutamide induced dose-dependent phototoxicity. Cells incubated with bendroflumethiazide, tolbutamide, and glibenclamide, and irradiated with UVA1 demonstrated an increased oxidative DNA damage. Pre-treatment with L-ascorbic acid, or (alpha) -tocopherol, suppressed the UVA-induced DNA damage in cells incubated with 1 mM of bendroflumethiazide, furosemide, glibenclamide, glipizide, tolbutamide, and trichloromethiazide, further implying the involvement of reactive oxygen species in the phototoxic DNA damage. These results may indicate a link between phototoxic and photocancerogenic potential of the sulfonamide-derived oral antidiabetic and diuretic drugs, as it has previously been recognized for psoralen, chlorpromazine, and fluoroquinolones. Excessive exposure to UV light may be deleterious for patients treated with these drugs.

Antidiabetic Activity of Aqueous Leaves Extract of Sesbania sesban (L) Merr. in Streptozotocin Induced Diabetic Rats

PubMed Central

Pandhare, Ramdas B.; Sangameswaran, B.; Mohite, Popat B.; Khanage, Shantaram G.

2011-01-01

The aqueous leaves extract of Sesbania sesban (L) Merr. (Family: Fabaceae) was evaluated for its antidiabetic potential on normal and streptozotocin (STZ)-induced diabetic rats. In the chronic model, the aqueous extract was administered to normal and STZ- induced diabetic rats at the doses of 250 and 500 mg/kg body weight (b.w.) p.o. per day for 30 days. The fasting Blood Glucose Levels (BGL), serum insulin level and biochemical data such as glycosylated hemoglobin, Total Cholesterol (TC), Triglycerides (TG), High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) were evaluated and all were compared to that of the known anti-diabetic drug glibenclamide (0.25 mg/kg b.w.). The statistical data indicated significant increase in the body weight, liver glycogen, serum insulin and HDL levels and decrease in blood glucose, glycosylated hemoglobin, total cholesterol and serum triglycerides when compared with glibenclamide. Thus the aqueous leaves extract of Sesbania sesban had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced diabetic rats. PMID:23407749

Therapeutic strategies to improve control of hypertension.

PubMed

Armario, Pedro; Waeber, Bernard

2013-03-01

Blood pressure is poorly controlled in most European countries and the control rate is even lower in high-risk patients such as patients with chronic kidney disease, diabetic patients or previous coronary heart disease. Several factors have been associated with poor control, some of which involve the characteristic of the patients themselves, such as socioeconomic factors, or unsuitable life-styles, other factors related to hypertension or to associated comorbidity, but there are also factors directly associated with antihypertensive therapy, mainly involving adherence problems, therapeutic inertia and therapeutic strategies unsuited to difficult-to-control hypertensive patients. It is common knowledge that only 30% of hypertensive patients can be controlled using monotherapy; all the rest require a combination of two or more antihypertensive drugs, and this can be a barrier to good adherence and log-term persistence in patients who also often need to use other drugs, such as antidiabetic agents, statins or antiplatelet agents. The fixed combinations of three antihypertensive agents currently available can facilitate long-term control of these patients in clinical practice. If well tolerated, a long-term therapeutic regimen that includes a diuretic, an ACE inhibitor or an angiotensin receptor blocker, and a calcium channel blocker is the recommended optimal triple therapy.

Joint effects of diabetic-related genomic loci on the therapeutic efficacy of oral anti-diabetic drugs in Chinese type 2 diabetes patients

PubMed Central

Chen, Miao; Zhang, Rong; Jiang, Feng; Wang, Jie; Peng, Danfeng; Yan, Jing; Wang, Shiyun; Wang, Tao; Bao, Yuqian; Hu, Cheng; Jia, Weiping

2016-01-01

Previous pharmacogenomic studies of oral anti-diabetic drugs have primarily focused on the effect of a single site. This study aimed to examine the joint effects of multiple loci on repaglinide or rosiglitazone efficacy in newly diagnosed type 2 diabetes mellitus (T2DM) patients. A total of 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks. The reductions in fasting glucose (ΔFPG), 2h glucose (Δ2hPG) and glycated hemoglobin (ΔHbA1c) levels were significantly associated with genetic score that was constructed using the sum of the effect alleles both in the repaglinide (P = 0.0011, 0.0002 and 0.0067, respectively) and rosiglitazone cohorts (P = 0.0002, 0.0014 and 0.0164, respectively) after adjusting for age, gender, body mass index and dosage. Survival analyses showed a trend towards a greater attainment rate of target HbA1c level in individuals with a high genetic score in the repaglinide cohort and rosiglitazone cohort (Plog-rank = 0.0815 and 0.0867, respectively) when the attainment of treatment targets were defined as more than 20% decrease of FPG, 2hPG, and HbA1c levels after treatment. In conclusion, we identified the joint effects of several T2DM-related loci on the efficacy of oral anti-diabetic drugs; moreover, we built a model to predict the drug efficacy. PMID:26983698

Anti-diabetic effect of cinnamon extract on blood glucose in db/db mice.

PubMed

Kim, Sung Hee; Hyun, Sun Hee; Choung, Se Young

2006-03-08

The anti-diabetic effect of Cinnamomi cassiae extract (Cinnamon bark: Lauraceae) in a type II diabetic animal model (C57BIKsj db/db) was studied. Cinnamon extract was administered at different dosages (50, 100, 150 and 200 mg/kg) for 6 weeks. It was found that blood glucose concentration is significantly decreased in a dose-dependent manner (P<0.001) with the most in the 200 mg/kg group compared with the control. In addition, serum insulin levels and HDL-cholesterol levels were significantly higher (P<0.01) and the concentration of triglyceride, total cholesterol and intestinal alpha-glycosidase activity were significantly lower after 6 weeks of the administration. These results suggest that cinnamon extract has a regulatory role in blood glucose level and lipids and it may also exert a blood glucose-suppressing effect by improving insulin sensitivity or slowing absorption of carbohydrates in the small intestine.

An adenovirus-derived protein: A novel candidate for anti-diabetic drug development.

PubMed

Hegde, Vijay; Na, Ha-Na; Dubuisson, Olga; Burke, Susan J; Collier, J Jason; Burk, David; Mendoza, Tamra; Dhurandhar, Nikhil V

2016-02-01

Exposure to human adenovirus Ad36 is causatively and correlatively linked with better glycemic control in animals and humans, respectively. Although the anti-hyperglycemic property of Ad36 may offer some therapeutic potential, it is impractical to use an infectious agent for therapeutic benefit. Cell-based studies identified that Ad36 enhances cellular glucose disposal via its E4orf1 protein. Ability to improve glycemic control in vivo is a critical prerequisite for further investigating the therapeutic potential of E4orf1. Therefore, the aim of this study was to determine the ability of E4orf1 to improve glycemic control independent of insulin despite high fat diet. 8-9wk old male C57BL/6J mice fed a high-fat diet (60% kcal) were injected with a retrovirus plasmid expressing E4orf1, or a null vector (Control). Glycemic control was determined by glucose and insulin tolerance test. Islet cell size, amount of insulin and glucagon were determined in formalin-fixed pancreas. Rat insulinoma cell line (832/13) was infected with E4orf1 or control to determine changes in glucose stimulated insulin secretion. Protein from flash frozen adipose tissue depots, liver and muscle was used to determine molecular signaling by western blotting. In multiple experiments, retrovirus-mediated E4orf1 expression in C57BL/6J mice significantly and reproducibly improved glucose excursion following a glucose load despite a high fat diet (60% energy). Importantly, E4orf1 improved glucose clearance without increasing insulin sensitivity, production or secretion, underscoring its insulin-independent effect. E4orf1 modulated molecular signaling in mice tissue, which included greater protein abundance of adiponectin, p-AKT and Glucose transporter Glu4. This study provides the proof of concept for translational development of E4orf1 as a potential anti-diabetic agent. High fat intake and impaired insulin signaling are often associated with obesity, diabetes and insulin resistance. Hence, the ability of E4orf1 to improve glycemic control despite high fat diet and independent of insulin, is particularly attractive. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

[Impact of anti-diabetic therapy based on glucagon-like peptide-1 receptor agonists on the cardiovascular risk of patients with type 2 diabetes mellitus].

PubMed

Camafort-Babkowski, Miguel

2013-08-17

Anti-diabetic drugs have, in addition to their well-known glucose lowering-effect, different effects in the rest of cardiovascular factors that are associated with diabetes mellitus. Glucagon-like peptide-1 (GLP-1) receptor agonists have recently been incorporated to the therapeutic arsenal of type 2 diabetes mellitus. The objective of this review is to summarize the available evidence on the effect of the GLP-1 receptor agonists on different cardiovascular risk factors, mediated by the effect of GLP-1 receptor agonists on the control of hyperglycaemia and the GLP-1 receptor agonists effect on other cardiovascular risk factors (weight control, blood pressure control, lipid profile and all other cardiovascular risk biomarkers). In addition, we present the emerging evidence with regards to the impact that GLP-1 receptor agonists therapy could have in the reduction of cardiovascular events and the currently ongoing studies addressing this issue. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Physicochemical and crystal structure analyses of the antidiabetic agent troglitazone.

PubMed

Kobayashi, Katsuhiro; Fukuhara, Hiroshi; Hata, Tadashi; Sekine, Akiko; Uekusa, Hidehiro; Ohashi, Yuji

2003-07-01

The antidiabetic agent troglitazone has two asymmetric carbons located at the chroman ring and the thiazolidine ring and is produced as a mixture of equal amounts of four optical isomers, 2R-5S, 2S-5R, 2R-5R, and 2S-5S. The crystalline powdered drug substance consists of two diastereomer pairs, 2R-5R/2S-5S and 2R-5S/2S-5R. There are many types of crystals obtained from various crystallization conditions. The X-ray structure analysis and the physicochemical analyses of troglitazone were performed. The solvated crystals of the 2R-5R/2S-5S pair were crystallized from several solutions: methanol, ethanol, acetonitrile, and dichloromethane. The ratio of solvent and troglitazone was 1 : 2 (L1/2-form). The monohydrate crystals were obtained from aqueous acetone solution (L1-form). On the other hand, only an anhydrate crystal of the 2R-5S/2S-5R pair was crystallized from various solutions (H0-form). The dihydrous mixed crystal (MA2-form) was obtained from a mixture of the two diastereomer pairs of 2R-5R/2S-5S and 2R-5S/2S-5R in equal amounts by the slow evaporation of aqueous acetone solution. The crystal structure of the MA2-form is similar to the H0-form. When the MA2 crystal was kept under low humidity, it was converted into the dehydrated form (MA0-form) with retention of the single crystal form. The structure of the MA0-form is isomorphous to the H0-form. The MA2-form was converted into the MA0-form and vice versa with retention of the single crystal under low and high humidity, respectively. The crystallization and storage conditions of the drug substances were successfully analyzed.

Initiation of insulin glargine therapy in type 2 diabetes subjects suboptimally controlled on oral antidiabetic agents: results from the AT.LANTUS trial.

PubMed

Davies, M; Lavalle-González, F; Storms, F; Gomis, R

2008-05-01

For many patients with type 2 diabetes, oral antidiabetic agents (OADs) do not provide optimal glycaemic control, necessitating insulin therapy. Fear of hypoglycaemia is a major barrier to initiating insulin therapy. The AT.LANTUS study investigated optimal methods to initiate and maintain insulin glargine (LANTUS, glargine, Sanofi-aventis, Paris, France) therapy using two treatment algorithms. This subgroup analysis investigated the initiation of once-daily glargine therapy in patients suboptimally controlled on multiple OADs. This study was a 24-week, multinational (59 countries), multicenter (611), randomized study. Algorithm 1 was a clinic-driven titration and algorithm 2 was a patient-driven titration. Titration was based on target fasting blood glucose < or =100 mg/dl (< or =5.5 mmol/l). Algorithms were compared for incidence of severe hypoglycaemia [requiring assistance and blood glucose <50 mg/dl (<2.8 mmol/l)] and baseline to end-point change in haemoglobin A(1c) (HbA(1c)). Of the 4961 patients enrolled in the study, 865 were included in this subgroup analysis: 340 received glargine plus 1 OAD and 525 received glargine plus >1 OAD. Incidence of severe hypoglycaemia was <1%. HbA(1c) decreased significantly between baseline and end-point for patients receiving glargine plus 1 OAD (-1.4%, p < 0.001; algorithm 1 -1.3% vs. algorithm 2 -1.5%; p = 0.03) and glargine plus >1 OAD (-1.7%, p < 0.001; algorithm 1 -1.5% vs. algorithm 2 -1.8%; p = 0.001). This study shows that initiation of once-daily glargine with OADs results in significant reduction of HbA(1c) with a low risk of hypoglycaemia. The greater reduction in HbA(1c) was seen in patients randomized to the patient-driven algorithm (algorithm 2) on 1 or >1 OAD.

Ibipinabant attenuates β-cell loss in male Zucker diabetic fatty rats independently of its effects on body weight.

PubMed

Rohrbach, K; Thomas, M A; Glick, S; Fung, E N; Wang, V; Watson, L; Gregory, P; Antel, J; Pelleymounter, M A

2012-06-01

To test the antidiabetic efficacy of ibipinabant, this new cannabinoid receptor 1 (CB1) antagonist was compared with food-restriction-induced weight loss, rosiglitazone (4 mg/kg) and rimonabant (3 and 10 mg/kg), using parameters of glycaemic control in male Zucker diabetic fatty (ZDF) rats. Body weight, food and water intake, fasted and non-fasted glucose and insulin, glucose tolerance and glycosylated haemoglobin (HbA1c) were all assessed over the course of the 9-week study. Pancreatic insulin content and islet area were also evaluated. At the end of the study, vehicle-treated ZDF rats were severely hyperglycaemic and showed signs of β-cell decline, including dramatic reductions in unfasted insulin levels. Ibipinanbant (10 mg/kg) reduced the following relative to vehicle controls: fasting glucose (-61%), glucose excursion area under the curve (AUC) in an oral glucose tolerance test (OGTT, -44%) and HbA1c (-50%). Furthermore, non-fasting insulin, islet area and islet insulin content were all increased (71, 40 and 76%, respectively) relative to vehicle controls by the end of the study. All of these effects were similar to those of rimonabant and rosiglitazone, where ibipinabant was slightly more effective than rimonabant at the lowest dose and somewhat less effective than rosiglitazone at all doses. These antidiabetic effects appear independent of weight loss because none of the parameters above were consistently improved by the comparable weight loss induced by food restriction. Ibipinabant may have weight loss-independent antidiabetic effects and may have the potential to attenuate β-cell loss in a model of progressive β-cell dysfunction. © 2012 Blackwell Publishing Ltd.

New therapeutic horizons: mapping the future of glycemic control with incretin-based therapy.

PubMed

Campbell, R Keith; Miller, Sara

2009-01-01

More than 24 million adults and children in the United States are living with diabetes, and the vast majority of those individuals have type 2 diabetes. The clinical benefits of good glycemic control have been well established. Most patients eventually require the use of multiple hyperglycemic drugs in combination to approach or achieve the American Diabetes Association's recommended target A1C value of 7%. The role of incretin-based therapies for both glycemic control and beta-cell protection has become an area of intense interest and development. Although current practice guidelines do not include specific recommendations about when and how to incorporate incretin-based agents, a consensus statement published by the American Diabetes Association/European Association for the Study of Diabetes suggests the addition of a glucagon-like peptide-1 (GLP-1) agonist for patients not at goal A1C with metformin and lifestyle changes. The goal of this article is to review this class of agents, discuss their role in the treatment of type 2 diabetes, and address the practical aspects of integrating incretin-based agents into the management of patients with diabetes. Currently, 3 incretin-based therapies are available and widely used in clinical practice. Several more agents are either under review by the Food and Drug Administration (FDA) or are in the very late stages of development. For diabetes educators trying to help their patients understand the differences among their antidiabetic medications, a comprehensive understanding of these agents and their role in therapy is imperative.

Tackling obesity: new therapeutic agents for assisted weight loss

PubMed Central

Karam, JG; McFarlane, SI

2010-01-01

The pandemic of overweight and obesity continues to rise in an alarming rate in western countries and around the globe representing a major public health challenge in desperate need for new strategies tackling obesity. In the United States nearly two thirds of the population is overweight or obese. Worldwide the number of persons who are overweight or obese exceeded 1.6 billion. These rising figures have been clearly associated with increased morbidity and mortality. For example, in the Framingham study, the risk of death increases with each additional pound of weight gain even in the relatively younger population between 30 and 42 years of age. Overweight and obesity are also associated with increased co-morbid conditions such as diabetes, hypertension and cardiovascular disease as well as certain types of cancer. In this review we discuss the epidemic of obesity, highlighting the pathophysiologic mechanisms of weight gain. We also provide an overview of the assessment of overweight and obese individuals discussing possible secondary causes of obesity. In a detailed section we discuss the currently approved therapeutic interventions for obesity highlighting their mechanisms of action and evidence of their efficacy and safety as provided in clinical trials. Finally, we discuss novel therapeutic interventions that are in various stages of development with a special section on the weight loss effects of anti-diabetic medications. These agents are particularly attractive options for our growing population of obese diabetic individuals. PMID:21437080

Discovery of an Isothiazole-Based Phenylpropanoic Acid GPR120 Agonist as a Development Candidate for Type 2 Diabetes.

PubMed

Zhang, Xuqing; Cai, Chaozhong; Sui, Zhihua; Macielag, Mark; Wang, Yuanping; Yan, Wen; Suckow, Arthur; Hua, Hong; Bell, Austin; Haug, Peter; Clapper, Wilma; Jenkinson, Celia; Gunnet, Joseph; Leonard, James; Murray, William V

2017-09-14

We have discovered a novel series of isothiazole-based phenylpropanoic acids as GPR120 agonists. Extensive structure-activity relationship studies led to the discovery of a potent GPR120 agonist 4x , which displayed good EC 50 values in both calcium and β-arrestin assays. It also presented good pharmaceutical properties and a favorable PK profile. Moreover, it demonstrated in vivo antidiabetic activity in C57BL/6 DIO mice. Studies in WT and knockout DIO mice showed that it improved glucose handling during an OGTT via GPR120. Overall, 4x possessed promising antidiabetic effect and good safety profile to be a development candidate.

A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects.

PubMed

Lee, Jae Man; Lee, Yoon Kwang; Mamrosh, Jennifer L; Busby, Scott A; Griffin, Patrick R; Pathak, Manish C; Ortlund, Eric A; Moore, David D

2011-05-25

Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.

The anti-diabetic effects of ethanol extract from two variants of Artemisia princeps Pampanini in C57BL/KsJ-db/db mice.

PubMed

Jung, U J; Baek, N-I; Chung, H-G; Bang, M-H; Yoo, J-S; Jeong, T S; Lee, K-T; Kang, Y J; Lee, M K; Kim, H J; Yeo, J Y; Choi, M S

2007-10-01

The anti-diabetic effects of two variants of Artemisia princeps Pampanini, sajabalssuk (SB) and sajuarissuk (SS), were investigated in type 2 diabetic animal using their ethanol extracts. Male C57BL/KsJ-db/db (db/db) mice were divided into control, SB ethanol extract (SBE), SS ethanol extract (SSE), or rosiglitazone (RG) groups and their age-matched littermates (db/+) were used. Supplementation of the SBE (0.171 g/100g diet), SSE (0.154 g/100g diet), and RG (0.005 g/100g diet) improved glucose and insulin tolerance and significantly lowered blood glycosylated hemoglobin levels, as compared to the control group. Plasma insulin, C-peptide and glucagon levels in db/db mice were higher in the db/+ mice, however these values were significantly lowered by SBE, SSE or RG-supplement. Hepatic GK activity was significantly lower in the db/db mice than in the db/+ mice, while hepatic G6Pase activity was vice versa. Supplementation of SBE, SSE and RG reversed these hepatic glucose-regulating enzyme activities. In addition, SBE and SSE markedly increased the hepatic glycogen content and muscle ratio as compared to the control group, but they did not alter the food intake, body weight and plasma leptin level. The RG group, however, showed a significant increase in the food intake, body weight and plasma leptin. These results suggest that SBE and SSE exert an anti-diabetic effect in type 2 diabetic mice.

Antidiabetic and Renoprotective Effects of Cladophora glomerata Kützing Extract in Experimental Type 2 Diabetic Rats: A Potential Nutraceutical Product for Diabetic Nephropathy

PubMed Central

Srimaroeng, Chutima; Ontawong, Atcharaporn; Saowakon, Naruwan; Vivithanaporn, Pornpun; Pongchaidecha, Anchalee; Amornlerdpison, Doungporn; Soodvilai, Sunhapas; Chatsudthipong, Varanuj

2015-01-01

Cladophora glomerata extract (CGE) has been shown to exhibit antigastric ulcer, anti-inflammatory, analgesic, hypotensive, and antioxidant activities. The present study investigated antidiabetic and renoprotective effects of CGE in type 2 diabetes mellitus (T2DM) rats. The rats were induced by high-fat diet and streptozotocin and supplemented daily with 1 g/kg BW of CGE for 12 weeks. The renal transport function was assessed by the uptake of para-aminohippurate mediated organic anion transporters 1 (Oat1) and 3 (Oat3), using renal cortical slices. These two transporters were known to be upregulated by insulin and PKCζ while they were downregulated by PKCα activation. Compared to T2DM, CGE supplemented rats had significantly improved hyperglycaemia, hypertriglyceridemia, insulin resistance, and renal morphology. The baseline uptake of para-aminohippurate was not different among experimental groups and was correlated with Oat1 and 3 mRNA expressions. Nevertheless, while insulin-stimulated Oat1 and 3 functions in renal slices were blunted in T2DM rats, they were improved by CGE supplementation. The mechanism of CGE-restored insulin-stimulated Oat1 and 3 functions was clearly shown to be associated with upregulated PKCζ and downregulated PKCα expressions and activations. These findings indicate that CGE has antidiabetic effect and suggest it may prevent diabetic nephropathy through PKCs in a T2DM rat model. PMID:25883984

Synthesis, Characterisation, Molecular Docking, Anti-microbial and Anti-diabetic Screening of Substituted 4-indolylphenyl-6-arylpyrimidine-2-imine Derivatives.

PubMed

Ramya, Veerasamy; Vembu, Santhirakasu; Ariharasivakumar, Ganesan; Gopalakrishnan, Manathusamy

2017-09-01

The purpose of the research is to synthesise a novel series of (E)-2-(4-(1H-indol-3-yl)-6-p-substituted phenylpyrimidin-2-yl)dimethylguanidine derivatives since 3-(1H-indol-3-yl)-1-p-substituted phenylprop-2-en-1-one and evaluate their molecular docking studies, antimicrobial, and anti-diabetic activities. Among all the synthesized compounds ( 11a-g ), compound 11a exhibits excellent CDOCKER energy (-11.36 kcal/mol). The entire compounds ( 11a-g ) confirm very good antimicrobial activity towards the tested microorganisms. In the in vitro anti-diabetic studies, compounds (11a, 11c, and 11g) confirm higher alpha-amylase and alpha-glucosidase inhibition activity. In the in vivo anti-diabetic activities, the synthesized compounds (11a-g) (10 mg/kg, p.o.) investigated by the streptozotocin (60 mg/kg, ip) -nicotinamide (120 mg/kg, p.o.) - induced model in adult male albino Wistar rat and these derivatives show considerable fasting blood glucose level when compared to metformin hydrochloride a potent and well-known anti-diabetic drug as a reference. © Georg Thieme Verlag KG Stuttgart · New York.

Therapeutic Potential of Pterocarpus santalinus L.: An Update

PubMed Central

Bulle, Saradamma; Reddyvari, Hymavathi; Nallanchakravarthula, Varadacharyulu; Vaddi, Damodara Reddy

2016-01-01

Recently there has been increasing interest in plants and plant-derived compounds as raw food and medicinal agents. In Ayurveda, an Indian system of traditional medicine, a wide spectrum of medicinal properties of Pterocarpus santalinus is described. Many important bioactive phytocompounds have been extracted and identified from the heartwood of P. santalinus. Bioactive compounds typically occur in small amounts and have more subtle effects than nutrients. These bioactive compounds influence cellular activities that modify the risk of disease rather than prevent deficiency diseases. A wide array of biological activities and potential health benefits of P. santalinus have been reported, including antioxidative, antidiabetic, antimicrobial, anticancer, and anti-inflammatory properties, and protective effects on the liver, gastric mucosa, and nervous system. All these protective effects were attributed to bioactive compounds present in P. santalinus. The major bioactive compounds present in the heartwood of P. santalinus are santalin A and B, savinin, calocedrin, pterolinus K and L, and pterostilbenes. The bioactive compounds have potentially important health benefits: These compounds can act as antioxidants, enzyme inhibitors and inducers, inhibitors of receptor activities, and inducers and inhibitors of gene expression, among other actions. The present review aims to understand the pharmacological effects of P. santalinus on health and disease with “up-to-date” discussion. PMID:27041873

Therapeutic Potential of Pterocarpus santalinus L.: An Update.

PubMed

Bulle, Saradamma; Reddyvari, Hymavathi; Nallanchakravarthula, Varadacharyulu; Vaddi, Damodara Reddy

2016-01-01

Recently there has been increasing interest in plants and plant-derived compounds as raw food and medicinal agents. In Ayurveda, an Indian system of traditional medicine, a wide spectrum of medicinal properties of Pterocarpus santalinus is described. Many important bioactive phytocompounds have been extracted and identified from the heartwood of P. santalinus. Bioactive compounds typically occur in small amounts and have more subtle effects than nutrients. These bioactive compounds influence cellular activities that modify the risk of disease rather than prevent deficiency diseases. A wide array of biological activities and potential health benefits of P. santalinus have been reported, including antioxidative, antidiabetic, antimicrobial, anticancer, and anti-inflammatory properties, and protective effects on the liver, gastric mucosa, and nervous system. All these protective effects were attributed to bioactive compounds present in P. santalinus. The major bioactive compounds present in the heartwood of P. santalinus are santalin A and B, savinin, calocedrin, pterolinus K and L, and pterostilbenes. The bioactive compounds have potentially important health benefits: These compounds can act as antioxidants, enzyme inhibitors and inducers, inhibitors of receptor activities, and inducers and inhibitors of gene expression, among other actions. The present review aims to understand the pharmacological effects of P. santalinus on health and disease with "up-to-date" discussion.

Preparation of S-Allylcysteine-Enriched Black Garlic Juice and Its Antidiabetic Effects in Streptozotocin-Induced Insulin-Deficient Mice.

PubMed

Kim, Jun Ho; Yu, Su Hyun; Cho, Yun Jeong; Pan, Jeong Hoon; Cho, Hyung Taek; Kim, Jeong Ho; Bong, Hyejin; Lee, Yeojin; Chang, Moon Han; Jeong, Ye Jin; Choi, Garam; Kim, Young Jun

2017-01-18

S-Allylcysteine (SAC), produced in large amounts during the aging process of garlic via enzymatic hydrolysis, is known as a key compound responsible for the multiple pharmacological activities of aged black garlic. This study investigated the effects of enzyme- and high hydrostatic pressure (HHP)-assisted extraction on the content of the bioactive compounds, including SAC, in black garlic juice (BGJ) and evaluated the antidiabetic effects of SAC-enriched BGJ in streptozotocin (STZ)-treated mice. The aging process increased the contents of SAC, total polyphenols, and total flavonoids in garlic juice. More importantly, pretreatment of pectinase cocktail with HHP resulted in a greater increase in those compounds during aging. Enzyme-treated BGJ reduced hyperglycemia and improved islet architecture and β-cell function in STZ-treated mice. Moreover, these effects were more potent than those of BGJ prepared by the conventional aging process. These findings provide useful information for the production of black garlic with improved bioactivities.

The Action of Antidiabetic Plants of the Canadian James Bay Cree Traditional Pharmacopeia on Key Enzymes of Hepatic Glucose Homeostasis

PubMed Central

Nachar, Abir; Vallerand, Diane; Musallam, Lina; Lavoie, Louis; Arnason, John; Haddad, Pierre S.

2013-01-01

We determined the capacity of putative antidiabetic plants used by the Eastern James Bay Cree (Canada) to modulate key enzymes of gluconeogenesis and glycogen synthesis and key regulating kinases. Glucose-6-phosphatase (G6Pase) and glycogen synthase (GS) activities were assessed in cultured hepatocytes treated with crude extracts of seventeen plant species. Phosphorylation of AMP-dependent protein kinase (AMPK), Akt, and Glycogen synthase kinase-3 (GSK-3) were probed by Western blot. Seven of the seventeen plant extracts significantly decreased G6Pase activity, Abies balsamea and Picea glauca, exerting an effect similar to insulin. This action involved both Akt and AMPK phosphorylation. On the other hand, several plant extracts activated GS, Larix laricina and A. balsamea, far exceeding the action of insulin. We also found a significant correlation between GS stimulation and GSK-3 phosphorylation induced by plant extract treatments. In summary, three Cree plants stand out for marked effects on hepatic glucose homeostasis. P. glauca affects glucose production whereas L. laricina rather acts on glucose storage. However, A. balsamea has the most promising profile, simultaneously and powerfully reducing G6Pase and stimulating GS. Our studies thus confirm that the reduction of hepatic glucose production likely contributes to the therapeutic potential of several antidiabetic Cree traditional medicines. PMID:23864882

Antidiabetic activity of flower buds of Michelia champaca Linn

PubMed Central

Jarald, E. Edwin; Joshi, S.B.; Jain, D.C.

2008-01-01

Objective: To identify the antihyperglycemic activity of various extracts, petroleum ether (60-80°), chloroform, acetone, ethanol, aqueous and crude aqueous, of the flower buds of Michelia champaca, and to identify the antidiabetic activity of active antihyperglycemic extract. Materials and Methods: Plant extracts were tested for antihyperglycemic activity in glucose overloaded hyperglycemic rats. The effective antihyperglycemic extract was tested for its hypoglycemic activity at two-dose levels, 200 and 400 mg/kg respectively. To confirm its utility in the higher model, the effective extract of M. champaca was subjected to antidiabetic study in alloxan induced diabetic model at two dose levels, 200 and 400 mg/kg respectively. The biochemical parameters, glucose, urea, creatinine, serum cholesterol, serum triglyceride, high density lipoprotein, low density lipoprotein, hemoglobin and glycosylated hemoglobin were also assessed in the experimental animals. Results: The ethanolic extract of M. champaca exhibited significant antihyperglycemic activity but did not produce hypoglycemia in fasted normal rats. Apart from this extract, the crude aqueous and petroleum ether extracts were found active only at the end of the first hour. Treatment of diabetic rats with ethanolic extract of this plant restored the elevated biochemical parameters significantly (P<0.05) (P<0.01) and the activity was found dose dependent. Conclusion: This study supports the traditional claim and the ethanolic extract of this plant could be added in traditional preparations for the ailment of various diabetes-associated complications. PMID:21279181

Hypoglycaemic effects of the novel antidiabetic agent repaglinide in rats and dogs

PubMed Central

Mark, Michael; Grell, Wolfgang

1997-01-01

Repaglinide, a novel compound with a nonsulphonylurea structure, is currently being clinically tested as a therapeutic agent. In the present study, the hypoglycaemic effects of repaglinide in rats and dogs were investigated. Whereas the R-enantiomer, AG-EE 624 ZW, showed only weak hypoglycaemic activity, the S-enantiomer, repaglinide, turned out to be a potent hypoglycaemic compound in rats after oral as well as after intravenous administration. Only 50% of the dose of repaglinide was needed to be equieffective with the racemic mixture AG-EE 388 ZW. The corresponding ED50 values calculated for the effects after 120 min p.a. (intravenous administration) were 3.4 μg kg−1 (repaglinide) and 6 μg kg−1 (AG-EE 388 ZW). When compared to glimepiride or glibenclamide, repaglinide displayed a 18 to 25 times higher potency in fasted rats. The ED50 values calculated for the effects after 120 min p.a. (oral administration) were 10 μg kg−1 (repaglinide), 182 μg kg−1 (glimepiride) and 255 μg kg−1 (glibenclamide). In glucose loaded rats (0.5, 1.0, 2.0 and 3.0 g kg−1 glucose, p.o.) repaglinide exerted a very strong antihyperglycaemic activity which was even more pronounced than under normoglycaemic conditions. So for a reduction in blood glucose of 1 mmol l−1, 10.3, 9.3, 7.0 8.4 and 7.2 μg kg−1 repaglinide were needed after glucose loads of 0.0, 0.5, 1.0, 2.0 and 3.0 g kg−1, respectively. In beagle dogs repaglinide again showed a pronounced hypoglycaemic effect (ED50 28.3 μg kg−1) which lasted for up to 24 h. However, insulin levels were only transiently increased. The in vivo data presented are well supported by recently published in vitro findings. From its activity profile, repaglinide appears to be a promising new therapeutic agent. PMID:9283692

Antidiabetic activity and phytochemical screening of extracts of the leaves of Ajuga remota Benth on alloxan-induced diabetic mice.

PubMed

Tafesse, Tadesse Bekele; Hymete, Ariaya; Mekonnen, Yalemtsehay; Tadesse, Mekuria

2017-05-02

Ajuga remota Benth is traditionally used in Ethiopia for the management of diabetes mellitus. Since this claim has not been investigated scientifically, the aim of this study was to evaluate the antidiabetic effect and phytochemical screening of the aqueous and 70% ethanol extracts on alloxan-induced diabetic mice. After acute toxicity test, the Swiss albino mice were induced with alloxan to get experimental diabetes animals. The fasting mean blood glucose level before and after treatment for two weeks in normal, diabetic untreated and diabetic mice treated with aqueous and 70% ethanol extracts were performed. Data were statistically evaluated by using Statistical Package for the Social Sciences software version 20. P-value <0.05 was considered statistically significant. The medium lethal doses (LD 50 ) of both extracts were higher than 5000 mg/kg, indicating the extracts are not toxic under the observable condition. Aqueous extracts of A.remota (300 mg/kg and 500 mg/kg body weight) reduced elevated blood glucose levels by 27.83 ± 2.96% and 38.98 ± 0.67% (P < 0.0001), respectively while the 70% ethanol extract caused a reduction of 27.94 ± 1.92% (300 mg/kg) & 28.26 ± 1.82% (500 mg/kg). Treatment with the antidiabetic drug, Glibenclamide (10 mg/kg body weight) lowered blood glucose level by 51.06% (p < 0.05). Phytochemical screening of both extracts indicated the presence of phenolic compounds, flavonoids, saponins, tannins, and steroids, which might contribute to the antidiabetic activity. The extracts, however, did not contain alkaloids and anthraquinones. The aqueous extract (500 mg/kg) showed the highest percentage reduction in blood glucose levels and the ability of A. remota extracts in reducing blood glucose levels presumably due to the presence of antioxidant constituents such as flavonoids. The effect of the extract supported the traditional claim of the plant.

Antidiabetic and antihyperlipidemic effects of ethanolic extract of leaves of Punica granatum in alloxan-induced non–insulin-dependent diabetes mellitus albino rats

PubMed Central

Das, Swarnamoni; Barman, Sarajita

2012-01-01

Objectives: Punica granatum L., (Family: Punicaceae) is used in Indian Unani medicine for treatment of diabetes mellitus. Therefore, the present study was done to evaluate the antidiabetic and antihyperlipidemic effects of ethanolic extract of leaves of P. granatum in alloxan-induced diabetic rats. Materials and Methods: Healthy Wistar albino rats (100-150 g) were divided into four groups of six animals each. Groups A and B received normal saline [(10 ml/kg/day/per oral (p.o.)]; group C received ethanolic extract of leaves of P. granatum (500 mg/kg/p.o.); and group D received glibenclamide (0.5 mg/kg/day/p.o.). The extracts were given for 1 week in all groups. To induce diabetes, alloxan 150 mg/kg, intraperitoneal (i.p.) single dose was administered to groups B, C, and D. Blood glucose and serum lipids [Total Cholesterol (TC), Triglycerides (TG), Low Density Lipoproteins (LDL), and High Density Lipoproteins (HDL)] and the atherogenic index were estimated after one week. For mechanism of antidiabetic action glycogen estimation on the liver, cardiac and skeletal muscle, and intestinal glucose absorption was done. Results: Group B showed a significant (P<0.01) increase in blood glucose as compared to group A. Groups C and D showed significant decrease (P<0.01) in blood glucose level in comparison to group B. The test drug showed a significant (P<0.01) increase in glycogen content in the liver, cardiac, and skeletal muscle; it significantly (P<0.01) reduced intestinal glucose absorption. Groups C and D showed significant (P<0.01) decrease in serum TC, TG, LDL, and AI as compared to Group B, which showed a significant (P<0.01) increase. Groups C and D showed significant (P<0.01) increase in serum HDL as compared to Group B, which showed a significant (P<0.01) decrease in all values. Conclusion: P. granatum leaves possess significant antidiabetic and antihyperlipidemic activity. PMID:22529479

The fatty acid-rich fraction of Eruca sativa (rocket salad) leaf extract exerts antidiabetic effects in cultured skeletal muscle, adipocytes and liver cells.

PubMed

Hetta, Mona H; Owis, Asmaa I; Haddad, Pierre S; Eid, Hoda M

2017-12-01

Eruca sativa Mill. (Brassicaceae), commonly known as rocket salad, is a popular leafy-green vegetable with many health benefits. To evaluate the antidiabetic activities of this plant in major insulin-responsive tissues. Five E. sativa leaf extracts of varying polarity were prepared (aqueous extract, 70% and 95% ethanol extracts, the n-hexane-soluble fraction of the 95% ethanol extract (ES3) and the defatted 95% ethanol extract). Eruca sativa extracts were investigated through a variety of cell-based in vitro bioassays for antidiabetic activities in C2C12 skeletal muscle cells, H4IIE hepatocytes and 3T3-L1 adipocytes. Guided by the results of these bioassays, ES3 was fractionated into the saponifiable (SM) and the unspaonifiable (USM) fractions. Glucose uptake was measured using [ 3 H]-deoxy-glucose, while the effects on hepatic glucose-6-phosphatase (G6Pase) and adipogenesis were assessed using Wako AutoKit Glucose and AdipoRed assays, respectively. ES3 and its SM fraction significantly stimulated glucose uptake with EC 50 values of 8.0 and 5.8 μg/mL, respectively. Both extracts significantly inhibited G6Pase activity (IC 50 values of 4.8 and 9.3 μg/mL, respectively). Moreover, ES3 and SM showed significant adipogenic activities with EC 50 of 4.3 and 6.1 μg/mL, respectively. Fatty acid content of SM was identified by GC-MS. trans-Vaccenic and palmitoleic acids were the major unsaturated fatty acids, while palmitic and azelaic acids were the main saturated fatty acids. These findings indicate that ES3 and its fatty acid-rich fraction exhibit antidiabetic activities in insulin-responsive cell lines and may hence prove useful for the treatment of type 2 diabetes.

Anti-diabetic effect of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) fruit acetone fraction in a type 2 diabetes model of rats.

PubMed

Mohammed, Aminu; Koorbanally, Neil Anthony; Islam, Md Shahidul

2016-03-02

In traditional medicine from West Africa, the fruit decoction of Xylopia aethiopica (Dunal) A. Rich. is widely used for the treatment of diabetes mellitus (DM) either alone or in combination with other plants. The present study is designed to investigate the anti-diabetic effects of X. aethiopica acetone fraction (XAAF) from fruit ethanolic extract in a type 2 diabetes (T2D) model of rats. T2D was induced in rats by feeding a 10% fructose solution ad libitum for 2 weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight) and the animals were orally treated with 150 or 300 mg/kg body weight (bw) of the XAAF once daily for four weeks. After 4 weeks study period, diabetic untreated animals (DBC) exhibited significantly higher serum glucose, serum fructosamine, LDH, CK-MB, serum lipids, liver glycogen, insulin resistance (HOMA-IR), AI, CRI and lower serum insulin, β-cell function (HOMA-β) and glucose tolerance ability compared to the normal animals. Histopathological examination of their pancreas revealed corresponding pathological changes in the islets and β-cells. These alterations were reverted to near-normal after the treatment of XAAF at 150 (DXAL) and 300 (DXAH) mg/kg bw with the effects being more pronounced in the DXAH group compared to the DXAL group. Moreover, the effects in the animals of DXAH group were comparable to the diabetic metformin (DMF) treated animals. In addition, no significant alterations were observed in non-diabetic animals treated with 300 mg/kg bw of XAAF (NXAH). The results of our study suggest that XAAF treatment showed excellent anti-diabetic effects in a T2D model of rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Antidiabetic effects of Cuscuta reflexa Roxb. in streptozotocin induced diabetic rats.

PubMed

Rath, Diptirani; Kar, Durga Madhab; Panigrahi, Sandeep Kumar; Maharana, Laxmidhar

2016-11-04

Cuscuta reflexa Roxb. (Convolvulaceae) is traditionally used to treat diabetes mellitus by tribal people of north-east India and Bangladesh. To evaluate the anti-diabetic effects of methanol and aqueous extracts of the aerial parts of Cuscuta reflexa Roxb. in normal, glucose loaded and Streptozotocin (STZ) induced diabetic rats. The methanol (MECR) and aqueous (AECR) extracts (200 and 400mg/kg body weight) were administered orally to normal and diabetic rats with Metformin and solvent control as comparison groups. Long term effects like FBG, OGTT, lipid profile, HbA1c, body weight, histopathology of major organs, etc. were investigated. MECR and AECR did not have hypoglycemic effects in normal rats. Both AECR and MECR (400mg/kg) treatments showed significant reduction in blood glucose during OGTT in diabetic rats at 3h. Single oral administration of methanol and aqueous extracts (400mg/kg) to diabetic rats significantly reduced (p<0.05) blood glucose level to 61.90% and 55.39% respectively as compared to the Metformin group i.e. 68.32% at the end of 8h. MECR (400mg/kg body weight for 30 days to diabetic rats) showed a significant decrease (p<0.01) of blood glucose level to 60.00% as compared to other groups. The treatment also resulted an improvement in body weights, decreased HbA1c and restored lipid profile. Histopathological injury was not observed, rather repair of beta cells was seen in extract treated diabetic rats. Methanolic extract of C. reflexa has significant antidiabetic effects and improves metabolic alterations thereby justifying its traditional folkloric claims. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[New drugs for small animals in 2014].

PubMed

Emmerich, I U

2015-01-01

In 2014, six active pharmaceutical ingredients were released on the German market for small animals. Those are the ektoparasiticide of the isoxazoline group afoxolaner (NexGard®) and fluralaner (Bravecto®) and the neonicotinoid dinotefuran (Vectra 3D, Vectra Felis), the antidiabetic protamine zinc insulin of human origin (ProZinc®), the antifungal agent ketoconazole (Fugazid®) as well as the cytostatic drug oclacitinib (Apoquel®). Two substances were authorized for an additional species. The antiparasiticide eprinomectin and the antibiotic clindamycin were also authorized for use in cats. In addition, two active pharmaceutical ingredients, which were approved 2014 for use in human medicine and are of potential interest to veterinary medicine, are discussed. These are the antihypertensive drug riociguat and the urological substance mirabegron.

The Effects of Glucose-Lowering Therapies on Diabetic Kidney Disease

PubMed Central

Agrawal, V.; Giri, C.; Solomon, R. J.

2015-01-01

Chronic hyperglycemia and its associated metabolic products are key factors responsible for the development and progression of diabetic chronic kidney disease (CKD). Endocrinologists are tasked with detection and management of early CKD before patients need referral to a nephrologist for advanced CKD or dialysis evaluation. Primary care physicians are increasingly becoming aware of the importance of managing hyperglycemia to prevent or delay progression of CKD. Glycemic control is an integral part of preventing or slowing the advancement of CKD in patients with diabetes; however, not all glucose-lowering agents are suitable for this patient population. The availability of the latest information on treatment options may enable physicians to thwart advancement of serious renal complication in patients suffering from diabetes. This review presents clinical data that shed light on the risk/benefit profiles of three relatively new antidiabetes drug classes, the dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 analogs, and sodium glucose co-transporter 2 inhibitors, particularly for patients with diabetic CKD, and summarizes the effects of these therapies on renal outcomes and glycemic control for endocrinologists and primary care physicians. Current recommendations for screening and diagnosis of CKD in patients with diabetes are also discussed. PMID:25824237

Experience with DPP-4 inhibitors in the management of patients with type 2 diabetes fasting during Ramadan

PubMed Central

Schweizer, Anja; Halimi, Serge; Dejager, Sylvie

2014-01-01

A large proportion of Muslim patients with type 2 diabetes mellitus (T2DM) elect to fast during the holy month of Ramadan. For these patients hypo- and hyperglycemia constitute two major complications associated with the profound changes in food pattern during the Ramadan fast, and efficacious treatment options with a low risk of hypoglycemia are therefore needed to manage their T2DM as effectively and safely as possible. Dipeptidyl peptidase-4 (DPP-4) inhibitors modulate insulin and glucagon secretion in a glucose-dependent manner, and consequently a low propensity of hypoglycemia has consistently been reported across different patient populations with these agents. Promising data with DPP-4 inhibitors have now also started to emerge in patients with T2DM fasting during Ramadan. The objective of this review is to provide a comprehensive overview of the currently available evidence and potential role of DPP-4 inhibitors in the management of patients with T2DM fasting during Ramadan whose diabetes is treated with oral antidiabetic drugs, and to discuss the mechanistic basis for their beneficial effects in this setting. PMID:24391442

Immunomodulatory and Antidiabetic Effects of a New Herbal Preparation (HemoHIM) on Streptozotocin-Induced Diabetic Mice

PubMed Central

Kim, Jong-Jin; Choi, Jina; Lee, Mi-Kyung; Kang, Kyung-Yun; Paik, Man-Jeong; Jo, Sung-Kee; Jung, Uhee; Park, Hae-Ran; Yee, Sung-Tae

2014-01-01

HemoHIM (a new herbal preparation of three edible herbs: Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia japonica Miyabe) was developed to protect immune, hematopoietic, and self-renewal tissues against radiation. This study determined whether or not HemoHIM could alter hyperglycemia and the immune response in diabetic mice. Both nondiabetic and diabetic mice were orally administered HemoHIM (100 mg/kg) once a day for 4 weeks. Diabetes was induced by single injection of streptozotocin (STZ, 200 mg/kg, i.p.). In diabetic mice, HemoHIM effectively improved hyperglycemia and glucose tolerance compared to the diabetic control group as well as elevated plasma insulin levels with preservation of insulin staining in pancreatic β-cells. HemoHIM treatment restored thymus weight, white blood cells, lymphocyte numbers, and splenic lymphocyte populations (CD4+ T and CD8+ T), which were reduced in diabetic mice, as well as IFN-γ production in response to Con A stimulation. These results indicate that HemoHIM may have potential as a glucose-lowering and immunomodulatory agent by enhancing the immune function of pancreatic β-cells in STZ-induced diabetic mice. PMID:25045390

[Effect of autogenic training on glucose regulation and lipid status in non-insulin dependent diabetics].

PubMed

Kostić, N; Secen, S

2000-01-01

The objective of this study was to examine the benefits of autogenic training in patients with type 2 diabetes and 40 diabetics treated with oral antidiabetic agents were assigned to receive autogenic training. Treatment effects on GHb levels, glycemia, lipids and lipid peroxidases were evaluated after 12 weeks. Subjects demonstrated significant improvements of GHb level (8.94 +/- 2.21% vs. 7.9 +/- 2.395) (p < 0.005). Fasting glucose was significantly lower after treatment (11.6 +/- 6.1 mmol/l vs. 8.32 +/- 4.53 mmol/l) (p < 0.005). The serum level of HDL cholesterol was significantly higher after autogenic training (1.21 +/- 0.11 vs. 1.36 +/- 1.42) (p < 0.005). Cholesterol level was significantly lower after training (6.63 +/- 1.66 mmol/l vs. 6.10 +/- 1.12 mmol/l) (p < 0.05). Lipid peroxidase was significantly lower after treatment (4.05 +/- 0.58 vs. 3.69 +/- 1.26) (p < 0.005). Autogenic training in selected patients, especially those who are most responsive to stress would provide benefits for glucosE control and lipid metabolism that are not always achieved by conventional treatment.

Modulatory effects of metformin on mutagenicity and epithelial tumor incidence in doxorubicin-treated Drosophila melanogaster.

PubMed

Oliveira, Victor Constante; Constante, Sarah Alves Rodrigues; Orsolin, Priscila Capelari; Nepomuceno, Júlio César; de Rezende, Alexandre Azenha Alves; Spanó, Mário Antônio

2017-08-01

Metformin (MET) is an anti-diabetic drug used to prevent hepatic glucose release and increase tissue insulin sensitivity. Diabetic cancer patients are on additional therapy with anticancer drugs. Doxorubicin (DXR) is a cancer chemotherapeutic agent that interferes with the topoisomerase II enzyme and generates free radicals. MET (2.5, 5, 10, 25 or 50 mM) alone was examined for mutagenicity, recombinogenicity and carcinogenicity, and combined with DXR (0.4 mM) for antimutagenicity, antirecombinogenicity and anticarcinogenicity, using the Somatic Mutation and Recombination Test and the Test for Detecting Epithelial Tumor Clones in Drosophila melanogaster. MET alone did not induce mutation or recombination. Modulating effects of MET on DXR-induced DNA damage were observed at the highest concentrations. In the evaluation of carcinogenesis, MET alone did not induce tumors. When combined with DXR, MET also reduced the DXR-induced tumors at the highest concentrations. Therefore, in the present experimental conditions, MET alone did not present mutagenic/recombinogenic/carcinogenic effects, but it was able to modulate the effect of DXR in the induction of DNA damage and of tumors in D. melanogaster. It is believed that this modulating effect is mainly related to the antioxidant, anti-inflammatory and apoptotic effects of this drug, although such effects have not been directly evaluated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Medicinal plants of the genus Anthocleista--A review of their ethnobotany, phytochemistry and pharmacology.

PubMed

Anyanwu, Gabriel O; Nisar-ur-Rehman; Onyeneke, Chukwu E; Rauf, Khalid

2015-12-04

The genus Anthocleista of the Gentianaceae family contains 14 species of trees and shrub-like plants distributed in tropical Africa, in Madagascar and on the Comoros. Traditionally, they are commonly used in the treatment of diabetes, hypertension, malaria, typhoid fever, obesity, diarrhea, dysentery, hyperprolactinemia, abdominal pain, ulcer, jaundice, asthma, hemorrhoids, hernia, cancer, wounds, chest pains, inflammations, rheumatism, STDs, infertility and skin diseases. They serve as an anthelmintic, laxative, diuretic and contraceptive. This review aims to provide for the first time a repository of ethnopharmacological information while critically evaluating the relation between the traditional medicinal uses, chemical constituents and pharmacological activities of the Anthocleista species so as to unveil opportunities for future research. A search for relevant information on Anthocleista species was performed on scientific databases (Pubmed, Google Scholar, SciFinder, Web of Science, Scopus, PubChem and other web sources such as The Plant List, Kew Botanical Garden and PROTA) and books, PhD and MSc dissertations for un-published resources. Out of the 14 species of Anthocleista, 6 have been reported in literature to be widely used in traditional medicine for the treatment of various ailments. The six species include: A. djalonensis, A. vogelii, A. nobilis, A. grandiflora, A. schweinfurthii, and A. liebrechtsiana. The chemical compounds isolated from Anthocleista species fall into the class of phytochemicals such as secoiridoids, nor-secoiridoids, xanthones, phytosterols, triterpenes, alkaloids, and others of which majority of the compounds were isolated from A. djalonensis and A. vogelii. The in vitro and in vivo pharmacological studies on the crude extracts, fractions and few isolated compounds of Anthocleista species showed antidiabetic, antiplasmodial, antimicrobial, hypotensive, spasmogenic, anti-obesity, antiulcerogenic, analgesic, anti-inflammatory, antioxidant, antitrypanosomal, anthelmintic, fertility, diuretic and laxative activities which supports most of their uses in traditional medicine. However, the bulk of the studies where centered on the antidiabetic, antiplasmodial and antimicrobial activities of Anthocleista species, although the evidence of its antiplasmodial effect was not convincing enough due to the discrepancies between the in vitro and in vivo results. A. djalonensis and A. vogelii are potential antidiabetic and antibacterial agents. The antibacterial potency relates to infections or diseases caused by E. coli, S. typhi and S. aureus such as urinary tract infections, typhoid, diarrhea, skin diseases, and food poisoning. Pharmacological research on this genus is quite elementary and limited, thus, more advanced research is necessary to isolate and determine the activities of bioactive compounds in vitro and in vivo, establish their mechanisms of action and commence the process of clinical research. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Biochemical Role of Macro and Micro-Minerals in the Management of Diabetes Mellitus and its Associated Complications: A Review.

PubMed

Mwiti Kibiti, Cromwell; Jide Afolayan, Anthony

2015-01-01

Diabetes mellitus is a chronic physiological glucose metabolic disorder. Its high prevalence globally has a significant impact on the quality of life. The management of diabetes includes non-pharmacological and glucose lowering agents. Although these methods are effective, they have drawbacks. This has led to a search for alternative therapy in macro and micro-minerals from dietary foods and plants. There is therefore a need to review, identify and classify their modes of action in diabetes mellitus therapy. This review was carried out using comprehensive literature reports on the use of mineral elements in the management of diabetes. Empirical online searches were conducted for different elements that have been studied for their anti-diabetic potentials both in vivo and in vitro. The University of Fort Hare's online database was also used. The results indicate that magnesium, molybdenum, zinc, vanadium and manganese facilitate glucose catabolism. Chromium, vanadium, zinc, molybdenum and magnesium can enhance insulin activity while molybdenum, manganese and zinc stimulate lipogenesis. Zinc and iron can modulate glucose, metabolizing enzymes in the gastrointestinal tract and limit oxidative stress, respectively. These agents have similar mechanisms to conventional drugs in ameliorating diabetic status and other associated complications. The mechanisms of these elements are well known, however, the synergetic effects of their combinations are still obscure. Literature on their safe dose(s) is still scanty. Evaluation of other useful macro and micro-minerals should also be undertaken. It is envisaged that the use of mineral supplements will promote good health in diabetics.

Hypoglycaemic and insulinotropic effects of a novel oral antidiabetic agent, (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166).

PubMed

Ikenoue, T; Akiyoshi, M; Fujitani, S; Okazaki, K; Kondo, N; Maki, T

1997-01-01

1. (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166), a novel oral hypoglycaemic agent is a non-sulphonylurea insulin secretagogue. 2. We investigated the insulin-releasing action and hypoglycaemic effect of A-4166 compared to sulphonylureas in vitro and in vivo. 3. A-4166 stimulated insulin secretion from rat freshly isolated pancreatic islets at concentrations from 3 x 10(-6) M to 3 x 10(-4) M in the presence of 2.8 mM glucose. There was no obvious difference in glucose dependency between the insulinotropic effect of A-4166 and that of glibenclamide, and no additive or synergistic effect was observed between these two drugs. 4. A-4166 displaced [3H]-glibenclamide bound to intact HIT-T15 cells in a concentration-dependent manner. The Ki value was 4.34 +/- 0.04 x 10(7) M, and the displacement potency of A-4166 was between that of glibenclamide and tolbutamide, being similar to that of gliclazide. 5. Inf fasted beagle dogs, A-4166 showed a dose-dependent hypoglycaemic effect after oral administration over the range 1 to 10 mg kg-1. The hypoglycaemic action of A-4166 showed an earlier onset and a shorter duration than that of sulphonylureas. 6. Simultaneous measurement of plasma insulin levels revealed that the hypoglycaemic effect of A-4166 was caused by a rapid-onset and brief burst of insulin secretion. 7. The pharmacokinetic profile of A-4166 was consistent with the changes of the blood glucose and plasma insulin levels. 8. Although the in vitro insulin-releasing effect of A-4166 was similar to that of sulphonylureas, its hypoglycaemic effect was more rapid and shorter-lasting, associated with rapid absorption and clearance. Thus, A-4166 may be useful in suppressing postprandial hyperglycaemia in patients with non-insulin-dependent diabetes mellitus.

Rosiglitazone Decreases C-Reactive Protein to a Greater Extent Relative to Glyburide and Metformin Over 4 Years Despite Greater Weight Gain

PubMed Central

Kahn, Steven E.; Haffner, Steven M.; Viberti, Giancarlo; Herman, William H.; Lachin, John M.; Kravitz, Barbara G.; Yu, Dahong; Paul, Gitanjali; Holman, Rury R.; Zinman, Bernard

2010-01-01

OBJECTIVE C-reactive protein (CRP) is closely associated with obesity and cardiovascular disease in both diabetic and nondiabetic populations. In the short term, commonly prescribed antidiabetic agents have different effects on CRP; however, the long-term effects of those agents are unknown. RESEARCH DESIGN AND METHODS In A Diabetes Outcome Progression Trial (ADOPT), we examined the long-term effects of rosiglitazone, glyburide, and metformin on CRP and the relationship among CRP, weight, and glycemic variables in 904 subjects over 4 years. RESULTS Baseline CRP was significantly correlated with homeostasis model assessment of insulin resistance (HOMA-IR), A1C, BMI, waist circumference, and waist-to-hip ratio. CRP reduction was greater in the rosiglitazone group by −47.6% relative to glyburide and by −30.5% relative to metformin at 48 months. Mean weight gain from baseline (at 48 months) was 5.6 kg with rosiglitazone, 1.8 kg with glyburide, and −2.8 kg with metformin. The change in CRP from baseline to 12 months was correlated positively with change in BMI in glyburide (r = 0.18) and metformin (r = 0.20) groups but not in the rosiglitazone (r = −0.05, NS) group. However, there was no longer a significant correlation between change in CRP and change in HOMA-IR, A1C, or waist-to-hip ratio in any of the three treatment groups. CONCLUSIONS Rosiglitazone treatment was associated with durable reductions in CRP independent of changes in insulin sensitivity, A1C, and weight gain. CRP in the glyburide and metformin groups was positively associated with changes in weight, but this was not the case with rosiglitazone. PMID:19808911

Rosiglitazone decreases C-reactive protein to a greater extent relative to glyburide and metformin over 4 years despite greater weight gain: observations from a Diabetes Outcome Progression Trial (ADOPT).

PubMed

Kahn, Steven E; Haffner, Steven M; Viberti, Giancarlo; Herman, William H; Lachin, John M; Kravitz, Barbara G; Yu, Dahong; Paul, Gitanjali; Holman, Rury R; Zinman, Bernard

2010-01-01

C-reactive protein (CRP) is closely associated with obesity and cardiovascular disease in both diabetic and nondiabetic populations. In the short term, commonly prescribed antidiabetic agents have different effects on CRP; however, the long-term effects of those agents are unknown. In A Diabetes Outcome Progression Trial (ADOPT), we examined the long-term effects of rosiglitazone, glyburide, and metformin on CRP and the relationship among CRP, weight, and glycemic variables in 904 subjects over 4 years. Baseline CRP was significantly correlated with homeostasis model assessment of insulin resistance (HOMA-IR), A1C, BMI, waist circumference, and waist-to-hip ratio. CRP reduction was greater in the rosiglitazone group by -47.6% relative to glyburide and by -30.5% relative to metformin at 48 months. Mean weight gain from baseline (at 48 months) was 5.6 kg with rosiglitazone, 1.8 kg with glyburide, and -2.8 kg with metformin. The change in CRP from baseline to 12 months was correlated positively with change in BMI in glyburide (r = 0.18) and metformin (r = 0.20) groups but not in the rosiglitazone (r = -0.05, NS) group. However, there was no longer a significant correlation between change in CRP and change in HOMA-IR, A1C, or waist-to-hip ratio in any of the three treatment groups. Rosiglitazone treatment was associated with durable reductions in CRP independent of changes in insulin sensitivity, A1C, and weight gain. CRP in the glyburide and metformin groups was positively associated with changes in weight, but this was not the case with rosiglitazone.