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1

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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. ...

2

Hypoglycemic effects of Potentilla fulgens L. in normal and alloxan-induced diabetic mice  

Microsoft Academic Search

Tap roots of Potentilla fulgens L. traditionally chewed along with betel nut (Areca catechu) and betel leaves (Piper betel), are commonly used by local practitioners for various types of ailments. The crude methanolic extract of the roots was tested for its effects in normoglycemic and alloxan-induced diabetic mice. Hypoglycemic activity was observed to be dose- and time- dependent. The extracts

D Syiem; G Syngai; P. Z Khup; B. S Khongwir; B Kharbuli; H Kayang

2002-01-01

3

Antihyperglycemic Effects of Fermented and Nonfermented Mung Bean Extracts on Alloxan-Induced-Diabetic Mice  

PubMed Central

Mung bean was reported as a potential antidiabetic agent while fermented food has been proposed as one of the major contributors that can reduce the risk of diabetes in Asian populations. In this study, we have compared the normoglycemic effect, glucose-induced hyperglycemic effect, and alloxan-induced hyperglycemic effect of fermented and nonfermented mung bean extracts. Our results showed that fermented mung bean extracts did not induce hypoglycemic effect on normal mice but significantly reduced the blood sugar levels of glucose- and alloxan-induced hyperglycemic mice. The serum levels of cholesterol, triglyceride (TG), and low-density lipoprotein (LDL) were also lowered while insulin secretion and antioxidant level as measured by malonaldehyde (MDA) assays were significantly improved in the plasma of the fermented mung bean-treated group in alloxan-induced hyperglycemic mouse. These results indicated that fermentation using Mardi Rhizopus sp. strain 5351 inoculums could enhance the antihyperglycemic and the antioxidant effects of mung bean in alloxan-treated mice. The improvement in the antihyperglycemic effect may also be contributed by the increased content of GABA and the free amino acid that are present in the fermented mung bean extracts. PMID:23091343

Yeap, Swee Keong; Mohd Ali, Norlaily; Mohd Yusof, Hamidah; Alitheen, Noorjahan Banu; Beh, Boon Kee; Ho, Wan Yong; Koh, Soo Peng; Long, Kamariah

2012-01-01

4

Effect of Potentilla fulgens on lipid peroxidation and antioxidant status in alloxan-induced diabetic mice.  

PubMed

Potentilla fulgens (Rosaceae) root traditionally used as a folk remedy by local health practitioners of Khasi Hills, Meghalaya was investigated for its effects on lipid peroxidation and antioxidant status in alloxan-induced diabetic mice. Significant increase in levels of thiobarbituric acid reactive substances (TBARS) and decrease in activities of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were observed under diabetic condition. Intraperitoneal administration of methanol extract of P. fulgens roots at a dose of 250 mg/kg body weight to male swiss albino diabetic mice for 14 days caused significant reduction in the elevated TBARS level, while increasing the activities of the antioxidant enzymes in diabetic mice. Maximum reduction in TBARS level was observed in liver tissue (75%, p<0.001). Kidney exhibited the highest elevation in the activity for catalase (68%, p<0.001) and superoxide dismutase (29%, p<0.001) while maximum increase in glutathione peroxidase activity was seen in brain (50%, p<0.001). The effects of P. fulgens was compared against known antioxidant, vitamin C. Results indicate that Potentilla fulgens methanolic root extract can reduce free radical mediated oxidative stress in experimental diabetes mellitus. PMID:24826032

Saio, Valrielyn; Syiem, Donkupar; Sharma, Ramesh

2012-03-01

5

Methanolic Root Extract of Rauwolfia serpentina Benth Improves the Glycemic, Antiatherogenic, and Cardioprotective Indices in Alloxan-Induced Diabetic Mice.  

PubMed

The aim of the study was to evaluate the phytochemistry and the effect of methanolic root extract (MREt) of Rauwolfia serpentina on alloxan-induced diabetic Wister male mice. Mice were divided in control (distilled water at 1?mL/kg) and alloxan-induced diabetic mice which subdivided into diabetic (distilled water at 1?mL/kg), negative (0.05% dimethyl sulfoxide at 1?mL/kg), positive (glibenclamide at 5?mg/kg) controls, and three test groups (MREt at 10, 30, and 60?mg/kg). All treatments were given orally for 14 days. Qualitatively MREt showed the presence of alkaloids, carbohydrates, flavonoids, glycosides, cardiac glycosides, phlobatannins, resins, saponins, steroids, tannins, and triterpenoids, while quantitatively extract was rich in total phenols. The flavonoids, saponins and alkaloids were also determined in root powder. MREt found effective in improving the body weights, glucose and insulin levels, insulin/glucose ratio, glycosylated and total hemoglobin in test groups as compared to diabetic control. Similarly, significantly decreased levels of total cholesterol, triglycerides, low-density lipoprotein (LDL-c), and very low-density lipoprotein (VLDL-c) cholesterols were found in test groups. Significant lipolysis with improved glycogenesis was also found in liver tissues of all test groups. ALT levels were found normal in all groups. Thus, MREt improves the glycemic, antiatherogenic, coronary risk, and cardioprotective indices in alloxan-induced diabetic mice. PMID:23365565

Azmi, Muhammad Bilal; Qureshi, Shamim A

2012-01-01

6

Methanolic Root Extract of Rauwolfia serpentina Benth Improves the Glycemic, Antiatherogenic, and Cardioprotective Indices in Alloxan-Induced Diabetic Mice  

PubMed Central

The aim of the study was to evaluate the phytochemistry and the effect of methanolic root extract (MREt) of Rauwolfia serpentina on alloxan-induced diabetic Wister male mice. Mice were divided in control (distilled water at 1?mL/kg) and alloxan-induced diabetic mice which subdivided into diabetic (distilled water at 1?mL/kg), negative (0.05% dimethyl sulfoxide at 1?mL/kg), positive (glibenclamide at 5?mg/kg) controls, and three test groups (MREt at 10, 30, and 60?mg/kg). All treatments were given orally for 14 days. Qualitatively MREt showed the presence of alkaloids, carbohydrates, flavonoids, glycosides, cardiac glycosides, phlobatannins, resins, saponins, steroids, tannins, and triterpenoids, while quantitatively extract was rich in total phenols. The flavonoids, saponins and alkaloids were also determined in root powder. MREt found effective in improving the body weights, glucose and insulin levels, insulin/glucose ratio, glycosylated and total hemoglobin in test groups as compared to diabetic control. Similarly, significantly decreased levels of total cholesterol, triglycerides, low-density lipoprotein (LDL-c), and very low-density lipoprotein (VLDL-c) cholesterols were found in test groups. Significant lipolysis with improved glycogenesis was also found in liver tissues of all test groups. ALT levels were found normal in all groups. Thus, MREt improves the glycemic, antiatherogenic, coronary risk, and cardioprotective indices in alloxan-induced diabetic mice. PMID:23365565

Azmi, Muhammad Bilal; Qureshi, Shamim A.

2012-01-01

7

Fermentation effects of oligosaccharides of Radix Ophiopogonis on alloxan-induced diabetes in mice.  

PubMed

In this study, oligosaccharides extracted from Ophiopogon japonicus vinegar (OOV) by alcoholic and acetic acid fermentation with water extracts from Radix Ophiopogon and oligosaccharides extracted from Radix Ophiopogonis (OOJ) were investigated. Characterization of the extracts indicated that OOV are proteoglycans, whereas OOJ are not. Moreover, compared with OOJ, monosaccharide compositions of OOV only include fructose and galactose and not glucose. MALDI-TOF-mass spectrometric results showed that the molecular weight of OOV was smaller after fermentation. Changes in the characteristics of OOV would inevitably lead to changes in its hypoglycemic properties. The OOV inhibition activity against ?-glucosidase was stronger than that of OOJ. The inhibition activity became stronger with higher dosages of OOV. The hypoglycemic effect of OOV on alloxan-induced diabetic mice was stronger than that of OOJ. More important, the ability of OOV to reduce damage on islets in diabetic mice was stronger than that of OOJ. Overall, alcoholic and acetic acid fermentation improved the hypoglycemic activity of OOJ. PMID:21549746

Lin, Wan-Ling; Su, Wei-Wei; Cai, Xue-Ying; Luo, Lv-Keng; Li, Pei-Bo; Wang, Yong-Gang

2011-08-01

8

The effect of cherry sticks extract on the levels of glycoproteins in alloxan-induced experimental diabetic mice.  

PubMed

This study was designed to evaluate the effect of ethanolic cherry sticks extract on the levels of glycoproteins in alloxan-induced diabetic mice. Forty-five adult male albino mice were divided equally into three groups: Group 1: control, Group 2: diabetic mice, Group 3: diabetic mice treated with cherry sticks extract as well as to eighteen mice treated with cherry sticks extract only for toxicity test. All treatments were administered via an intragastric tube. Diabetes was induced in the mice of Group 3 by an intraperitoneal injection with 100 mg/kg body weight of alloxan. Oral administration of cherry sticks extract at a concentration of 250 mg/kg body weight for 15 days significantly reduced the levels of blood glucose, glycosylated hemoglobin, urea, and creatinine as well as those of hexose, hexosamine, fucose, and sialic acid in the diabetic mice treated with the cherry sticks extract as compared to untreated diabetic mice, with no adverse effects in mice treated only with cherry sticks extract. In conclusion, cherry sticks extract proved to have a beneficial effect on the diabetic mice in this study. In light of these advantageous results, it is advisable to broaden the scale of use of cherry sticks extract in a trial to alleviate the adverse effects of diabetes. PMID:22371908

Sulaiman, Ghassan M; Al-Amiery, Ahmed A H; Mohammed, Abbas A; Al-Temimi, Ali A

2012-01-01

9

Lectin from Crataeva tapia Bark Improves Tissue Damages and Plasma Hyperglycemia in Alloxan-Induced Diabetic Mice  

PubMed Central

Crataeva tapia is a plant popularly used for diabetes treatment, in Brazil. Progressive decline in renal and hepatic functions has been described in patients with diabetes mellitus, and mortality rate is increased in patients with chronic liver and renal disease. This study aimed to evaluate whether Crataeva tapia bark lectin (CrataBL) improves hyperglycemia and renal and hepatic damage in diabetic mice. CrataBL was purified by ion exchange chromatography on CM-cellulose, and intraperitoneal administration of CrataBL to alloxan-induced diabetic mice at dose of 10?mg/Kg/day and 20?mg/Kg/day for 10 days significantly reduced serum glucose levels by 14.9% and 55.9%, respectively. Serum urea, creatinine, aspartate aminotransferase, and alanine aminotransferase were also significantly reduced after treatment with both doses of CrataBL. Furthermore, histological analysis of liver, kidney, and pancreas revealed an improvement in the tissue morphology upon treatment with CrataBL. The results suggest that CrataBL has a beneficial hypoglycemic activity and improves the renal and hepatic complications of diabetes. Therefore, this lectin may be a promising agent for the treatment of diabetes, and this might be the basis for its use in the folk medicine as an alternative treatment to manage diabetes-related complications such as hyperglycemia and tissue damage. PMID:24324521

da Rocha, Amanda Alves; Araújo, Tiago Ferreira da Silva; da Fonseca, Caíque Silveira Martins; da Mota, Diógenes Luís; de Medeiros, Paloma Lys; Paiva, Patrícia Maria Guedes; Coelho, Luana Cassandra Breitenbach Barroso; Correia, Maria Tereza dos Santos; Lima, Vera Lúcia de Menezes

2013-01-01

10

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

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

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

2014-01-01

11

Effect of Momordica grosvenori on oxidative stress pathways in renal mitochondria of normal and alloxan-induced diabetic mice  

Microsoft Academic Search

Background  Oxidative stress plays an important role in the pathogenesis of diabetes and diabetic nephropathy. Momordica grosvenori (MG), a traditional medicinal herb used as substitute sugar for obese and diabetes, exhibits anti-oxidative activity in vitro.\\u000a \\u000a \\u000a \\u000a Aim of the study  This study investigated the effect of MG on renal mitochondrial lipid peroxidation, anti-oxidative defense system, and a potent\\u000a oxidative stress–responsive protein, heme oxygenase-1

Fangfang Song; Xiangyang Qi; Weijun Chen; Wenbo Jia; Ping Yao; Andreas K. Nussler; Xiufa Sun; Liegang Liu

2007-01-01

12

Expression of visfatin in alloxan-induced diabetic rat testis.  

PubMed

Diabetes mellitus is a potential epidemic all over the world and causes dysfunction of reproductive activity. Visfatin, one of the adipokines, is present in various tissues including the testis. Our hypothesis was the level of testicular visfatin is affected in diabetic condition. The aim of the present study was to investigate the expression and localization of visfatin in the diabetic rat testis. No similar studies have been performed in diabetic rat testis with reference to visfatin. Overnight fasted adult male Wistar rats were made diabetic by the administration of alloxan (150 mg/kg i.p., in 0.9% saline). Blood glucose levels were tested on five days after alloxan treatment, rats with high blood glucose levels (>250 mg/dL) were considered as diabetic. Immunolocalization and Western blotting analysis of visfatin were performed. Correlation of visfatin expression was made in relation to body weight, testis weight, glucose concentration and serum testosterone level. Expression of visfatin was observed in Leydig cells, spermatocytes and sperm in control as well as in the diabetic group. Mild immunostaining of visfatin was observed in affected seminiferous tubules of alloxan-induced diabetic rat testis. Western blot analysis showed decreased expression of testicular visfatin in diabetic rats. The expression of visfatin showed a positive correlation with serum testosterone levels, body and testis weight, while a negative correlation was observed with blood glucose levels. This study showed involvement of visfatin in diabetic associated impairment of testicular activity. PMID:25450901

Gurusubramanian, Guruswami; Roy, Vikas Kumar

2014-10-01

13

Hypoglycaemic effect of galactooligosaccharides in alloxan-induced diabetic rats.  

PubMed

This study was conducted to assess the effect of prebiotic galactooligosaccharides (GOS) on alloxan-induced diabetes in male Sprague-Dawley (SD) rats. Diabetes was induced by administration of alloxan (100 mg/kg) and rats were divided in 4 groups: normal control group (NCG), prebiotic control group (PCG), diabetic control group (DCG) and diabetic prebiotic group (DPG). While PCG and DPG were fed with GOS supplemented (10% w/w) diet, NCG and DCG were administered with basal diet. Rats were sacrificed after 42 d for collection of blood and liver. Faecal samples were collected at the interval of 7 d throughout the study for measurement of lactobacilli and coliform count. Feeding of GOS decreased or delayed the severity of diabetes by amelioration of diabetes associated markers including fasting blood glucose, haemoglobin, glycosylated haemoglobin triglycerides, total cholesterol, low density lipoproteins, creatinine and urea. GOS was also found to improve the levels of antioxidative enzymes (superoxide dismutase, catalase and glutathione peroxidase) in liver and blood. Improvement in lactobacilli count along with a concomitant decrease in coliform count was observed in GOS fed groups. PMID:25382051

Sangwan, Vikas; Tomar, Sudhir K; Ali, Babar; Singh, Ram R B; Singh, Ashish K

2015-02-01

14

Antihyperglycemic and antihyperlipidemic effects of Clitoria ternatea Linn. in alloxan-induced diabetic rats  

Microsoft Academic Search

This study aims to investigate the therapeutic effects of Clitoria ternatea Linn. leaves and flowers extract on alloxan-induced diabetic rats. The effect of aqueous extract of C. ternatea leaves and flowers on serum glucose, glycosylated hemoglobin, insulin, total cholesterol, triglycerides, HDL-cholesterol, protein, urea, creatinine were examined in control and extract treated diabetic rats. Glycogen was examined both in the liver

P. Daisy; Kanakappan Santosh; M. Rajathi

15

Antihyperglycemic and antilipidperoxidative effects of Pongamia pinnata (Linn.) Pierre flowers in alloxan induced diabetic rats.  

PubMed

Our aim was to evaluate the antihyperglycemic and antilipid peroxidative effect of ethanolic extract of Pongamia pinnata (Linn.) Pierre (Leguminosae) flowers (PpEt) in normal rats and alloxan induced diabetic rats. Hyperglycemia, elevated lipid peroxidation [thiobarbituric acid reactive substances (TBARS)] and disturbed nonenzymatic [Vitamin E, Vitamin C and glutathione] and enzymatic antioxidants status were noticed in alloxan induced diabetic rats. The oral administration of ethanolic extract of Pongamia pinnata flowers (300 mg/kg bw) showed significant antihyperglycemic, and antilipidperoxidative effects and enhancement in antioxidants defense system in alloxan induced diabetic rats. However, no significant characteristic changes were noticed in blood glucose level as well as in lipid peroxidation and antioxidant status in normal rats treated with "PpEt" alone. We have also observed that the "PpEt" considerably reduced the blood glucose concentration in a similar extent to that of the reference drug glibenclamide (600 microg/kg bw) in alloxan induced diabetic rats. Our results thus suggested that the "PpEt" could be used as a safe alternative antihyperglycemic drug for diabetic patients. PMID:16271443

Punitha, R; Manoharan, S

2006-04-21

16

Effect of water extract of Psidium guajava leaves on alloxan-induced diabetic rats.  

PubMed

A water extract of Psidium guajava leaves was screened for hypoglycemic activity on alloxan-induced diabetic rats. In both acute and sub-acute tests, the water extract, at an oral dose of 250 mg/kg, showed statistically significant hypoglycemic activity. PMID:15497764

Mukhtar, H M; Ansari, S H; Ali, M; Naved, T; Bhat, Z A

2004-09-01

17

The Control of Hyperglycemia by Estriol and Progesterone in Alloxan induced Type I Diabetes Mellitus Mice Model through Hepatic Insulin Synthesis  

PubMed Central

As much as 20% of the women in menopause are reported to develop type I diabetes mellitus. The cessation of the ovarian syntheses of the female sex hormones is known to cause menopause in women, and the roles of estriol (one of the most abundant estrogens) and progesterone were investigated for hepatic insulin synthesis through estriol and progesterone induced synthesis of nitric oxide in the liver cells. Type 1 Diabetic mellitus mice were prepared by alloxan treatment, Nitric oxide was determined by methemoglobin method. Insulin was determined by enzyme linked immunosorbant assay. Injection of either 3.5 µM estriol or 3.5 nM progesterone to the diabetic mice which cannot synthesize pancreatic insulin, reduced the blood glucose level from 600 mg/dl to 120 mg/dl and 500 ± 25 mg/dl to 120 ± 6 mg/dl in 6 and 10 h respectively with simultaneous increase of the plasma insulin from 0 µunits/ml to 40 µunits/ml and 0 µunits/ml to 9.5 µunits/ml in the case of estriol and progesterone respectively with stimulated NO synthesis. The inhibition of the steroids induced NO synthesis by using NAME (NG-methyl-l-arginine acetate ester) in the reaction mixture resulted in the inhibition of hepatic insulin synthesis. Use of pure NO solution in 0.9% NaCl instead of either estriol or progesterone in the reaction mixture was found to stimulate the hepatic insulin synthesis. Both estriol and progesterone might be involved in the prevention of type 1 diabetes mellitus through the hepatic insulin synthesis even when the pancreatic insulin synthesis was impaired. PMID:24711743

Bhattacharya, Suman; Bank, Sarbashri; Maiti, Smarajit; Sinha, Asru K.

2014-01-01

18

Antihyperglycemic and Antihyperlipidemic Activity of Plectranthus Amboinicus on Normal and Alloxan-Induced Diabetic Rats  

PubMed Central

The present study was undertaken to investigate the antihyperglycemic and antihyperlipidemic effects of ethanol extract of Plectranthus amboinicus in normal and alloxan-induced diabetic rats. Diabetes was induced in Wistar rats by single intraperitoneal administration of alloxan monohydrate (150 mg/kg). Normal as well as diabetic rats were divided into groups (n=6) receiving different treatments. Graded doses (200 mg/kg and 400 mg/kg) of ethanol extract of Plectranthus amboinicus were studied in both normal and alloxan-induced diabetic rats for a period of 15 days. Glibenclamide (600 ?g/kg) was used as a reference drug. Oral administration with graded doses of ethanol extract of Plectranthus amboinicus exhibited hypoglycemic effect in normal rats and significantly reduced the peak glucose levels after 120 min of glucose loading. In alloxan-induced diabetic rats, the daily oral treatment with ethanol extract of Plectranthus amboinicus showed a significant reduction in blood glucose. Besides, administration of ethanol extract of Plectranthus amboinicus for 15 days significantly decreased serum contents of total cholesterol, triglycerides whereas HDL-cholesterol, total proteins and calcium were effectively increased. Furthermore, effect of ethanol extract of Plectranthus amboinicus showed profound elevation of serum amylase and reduction of serum lipase. Histology examination showed ethanol extract of Plectranthus amboinicus exhibited almost normalization of damaged pancreatic architecture in rats with diabetes mellitus. Studies clearly demonstrated that ethanol extract of Plectranthus amboinicus leaves possesses hypoglycemic and antihyperlipidemic effects mediated through the restoration of the functions of pancreatic tissues and insulinotropic effect. PMID:22303055

Viswanathaswamy, A. H. M.; Koti, B. C.; Gore, Aparna; Thippeswamy, A. H. M.; Kulkarni, R. V.

2011-01-01

19

Hypoglycemic and other related effects of Boswellia glabra in alloxan-induced diabetic rats.  

PubMed

The hypoglycemic effect of the aqueous extract of the leaves and roots of Boswellia glabra was examined using alloxan-induced diabetic rats. A single oral administration of Boswellia glabra leaf and root extract decreased the blood glucose level. The continued use of leaf and root extract for 28 days produced significant hypoglycemic effects; also there was a decrease in serum glucose, cholesterol, triglyceride, urea and creatinine levels and enzyme activities (alkaline phosphatase and glucose-6-phosphatase). Ultra structural studies of beta cell of alloxan-induced diabetic rats treated with root extract showed numerous granulated sacs in comparison to rats treated with leaf extract. Thus, rats treated with root extract showed less degranulated sacs and more number of filled secretory granules in comparison to diabetic rats. Thus the use of aqueous extract of Boswellia glabra increased the synthesis of secretory granules in the beta-cell. PMID:17877290

Kavitha, J V; Rosario, Joseph F; Chandran, J; Anbu, P; Bakkiyanathan

2007-01-01

20

Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats.  

PubMed

The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level. PMID:22557305

Sathya, S; Kokilavani, R; Gurusamy, K

2008-10-01

21

Early Renal Histological Changes in Alloxan-Induced Diabetic Rats  

PubMed Central

Diabetes mellitus is a progressive disease. Most investigators have focused on glomerular changes in diabetic kidney and non-glomerular alterations have been less attended. The present study has been conducted to find early non-glomerular histological changes in diabetic renal tissue. Twenty male Wistar rats weighting 200-250 g were used for the diabetic group. Diabetes mellitus was induced by single injection of Alloxan. After 8 weeks, paraffin embedded blocks of kidneys were prepared for evaluating the histological changes due to diabetes. Histological study showed the deposit of eosinophilic materials in the intermediate substantial of medulla and thickening of renal arterial wall in the kidney of 70% of diabetic rats. The average weight of kidneys increased when compared to non diabetic animals. Furthermore, the amount of blood flow in arteries of all diabetic kidneys has been enhanced. The present study demonstrates some early renal histological changes in diabetes mellitus which were earlier compared to those reported previously. Diabetic nephropathy is a progressive disease and renal care design can help better prognosis achievement. PMID:24551816

Pourghasem, Mohsen; Nasiri, Ebrahim; Shafi, Hamid

2014-01-01

22

Antidiabetic and antihyperlipidemic effects of Thespesia populnea fruit pulp extracts on alloxan-induced diabetic rats  

PubMed Central

Present study was carried to find out the antihyperglycemic and antihyperlipidemic activity of ethanol and aqueous extract of Thespesia populnea fruit pulp on alloxan-induced diabetic rats. Diabetes was induced in rats by administration of alloxan (150 mg/kg, i.p.). After the successful induction of experimental diabetes, the rats were divided into five groups each comprising a minimum of six rats. Phytochemical analysis and acute toxicity study of extracts was also done. The effects of extracts and metformin on fasting blood glucose and plasma lipid were examined for 28 days. Statistical analysis was carried out by using analysis of variance followed by Dunnet's multiple comparison test and paired t-test were done as the test of significance using GraphPad Prism. P?0.05 was considered as the minimal level of statistical significance. Therapeutic dose of extract was found to be 200 mg/kg on the basis of acute toxicity study. Aqueous and alcoholic extract showed a significant reduction in blood glucose levels as well as a lipid profile of diabetic rats at the end of 28th day of treatment. However, in groups treated with plant extract the reduction in the blood glucose and improvement in lipid profile was slightly less than that achieved with the standard group (metformin). From this study, it can be concluded that ethanol and aqueous extract of Thespesia populnea exhibited significant antihyperglycemic and antihyperlipidemic effects on alloxan-induced diabetic rats. PMID:24019572

Belhekar, S. N.; Chaudhari, P. D.; Saryawanshi, J. S.; Mali, K. K.; Pandhare, R. B.

2013-01-01

23

Assessment of wound healing in the alloxan-induced diabetic rabbit ear model.  

PubMed

The enhancement of diabetic wound healing represents a major clinical challenge to researchers. The challenge faced is to identify a suitable animal model that best represents the human situation. However, the majority of diabetic wound healing models are in rodents and are hindered by rapid contraction and thus do not reflect epithelial cell migration, as seen in the human wound. The alloxan-induced diabetic rabbit model is a cheap, reproducible model and offers the advantage of providing a noncontractile avascular wound bed. This study aimed to compare the effects of acute hyperglycemia in the alloxan model to normal rabbit controls on wound healing, using methods of stereology. Alloxan was administered 7 days prior to surgery. Four full-thickness punch biopsy wounds were created on each ear (n = 4). Wounds were excised at 7 and 14 days and prepared for stereological analysis from Masson's trichrome-stained histological sections. It was noted that the alloxan-treated animals showed an increase in the number of inflammatory cells and fibroblasts at 14 days. In addition, it was noted that the length density of blood vessels was reduced in the alloxan-induced diabetic rabbits, representing a greater radial diffusion distance between vessels and a less efficient network for nutrient exchange. This is the first study to take a stereological approach to defining the effects of diabetes mellitus on wound healing in a noncontractile model. PMID:19160134

Breen, Ailish; Mc Redmond, G; Dockery, P; O'Brien, T; Pandit, A

2008-01-01

24

Antidiabetic and antihyperlipidemic effects of Thespesia populnea fruit pulp extracts on alloxan-induced diabetic rats.  

PubMed

Present study was carried to find out the antihyperglycemic and antihyperlipidemic activity of ethanol and aqueous extract of Thespesia populnea fruit pulp on alloxan-induced diabetic rats. Diabetes was induced in rats by administration of alloxan (150 mg/kg, i.p.). After the successful induction of experimental diabetes, the rats were divided into five groups each comprising a minimum of six rats. Phytochemical analysis and acute toxicity study of extracts was also done. The effects of extracts and metformin on fasting blood glucose and plasma lipid were examined for 28 days. Statistical analysis was carried out by using analysis of variance followed by Dunnet's multiple comparison test and paired t-test were done as the test of significance using GraphPad Prism. P?0.05 was considered as the minimal level of statistical significance. Therapeutic dose of extract was found to be 200 mg/kg on the basis of acute toxicity study. Aqueous and alcoholic extract showed a significant reduction in blood glucose levels as well as a lipid profile of diabetic rats at the end of 28(th) day of treatment. However, in groups treated with plant extract the reduction in the blood glucose and improvement in lipid profile was slightly less than that achieved with the standard group (metformin). From this study, it can be concluded that ethanol and aqueous extract of Thespesia populnea exhibited significant antihyperglycemic and antihyperlipidemic effects on alloxan-induced diabetic rats. PMID:24019572

Belhekar, S N; Chaudhari, P D; Saryawanshi, J S; Mali, K K; Pandhare, R B

2013-03-01

25

Antihyperglycemic and hypolipidemic effects of Hibiscus schizopetalus (Mast) Hook in alloxan-induced diabetic rats.  

PubMed

The antihyperglycemic and hypolipidemic activities of Hibiscus schizopetalus (Mast) Hook (Malvaceae) flower and leaves extracts were investigated in alloxan-induced diabetic rats. The hypoglycemic activity of both the extracts (100mg/kg, body weight) was tested in fasting normal rat, glucose loaded rats. Observation on body weight was also recorded. The extracts showed a significant (p<0.001) reduction in blood glucose level in normal fasting rats. In glucose tolerance test, significant (p<0.01) decreased observed in all glucose loaded animals. While in alloxan induced diabetic rats, the percent blood glucose reduction was 59.94% and 45.14% in extracts treated groups. The results obtained were compared with the reference standard drug Tolbutamide (100mg/kg, body weight). The diabetic rats showed sign of decreased in their body weight during the treatment period. Cholesterol and triglycerides levels were significantly decreased (p<0.001) by HFE. The results obtained demonstrated the potential hypoglycemic activity of methanolic extracts of H. schizopetalus. There is need of bioassay-directed assay of the active principles responsible for the anti-diabetic activity. The methanolic extracts showed the presence of carbohydrates, alkaloids, steroids, terpenes, saponins and glycosides. PMID:24374457

Zahid, Hina; Rizwani, Ghazala H; Shareef, Huma; Khursheed, Raheela; Huma, Ambreen; Hasan, S M Farid

2014-01-01

26

Antidiabetic Effect of Sida cordata in Alloxan Induced Diabetic Rats  

PubMed Central

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. PMID:25114914

Shah, Naseer Ali; Khan, Muhammad Rashid

2014-01-01

27

Histological changes and antidiabetic activities of Icacina trichantha tuber extract in beta-cells of alloxan induced diabetic rats  

PubMed Central

Objective To investigate the antidiabetic, hypolipidaemic activities and histopathological changes of Icacina trichantha (I. trichantha) tuber extract in alloxan induced diabetic rats. Methods In the present study, 80% methanol extract of I. trichantha tuber was tested on alloxan induced diabetic rats. They were randomly grouped into control (distilled water and glibenclamide) and experimental (200, 400 and 600 mg/kg body weight). Diabetes was induced by a single intraperitoneal injection of 160 mg/kg body weight of alloxan. Blood glucose levels were measured using blood glucose test strips with AccuCheck Advantage II glucometer at 1, 3, 6, and 24 h on the first day and 1 h after treatment on Day 7, 14 and 21. Blood samples were collected and centrifuged to separate serum for estimation of lipid profile and other biochemical parameters. Histopathological changes in diabetic rats pancreas were also studied after extract treatment. Results Daily oral administration of I. trichantha tuber extract (200, 400, and 600 mg/kg body weight) and glibenclamide (2 mg/kg) showed beneficial effects on blood glucose level (P<0.01) as well as improving liver, kidney functions and hyperlipidaemia due to diabetes. The extract had a favourable effect on the histopathological changes of the pancreas in alloxan induced diabetes. Conclusions I. trichantha tuber extracts posses antidiabetic activities as well as improve liver and renal profile and total lipids levels. I. trichantha tuber extracts also have favourable effects to inhibit the histopathological changes of the pancreas in alloxan induced diabetes. PMID:23905020

Monday, Onakpa Michael; Uzoma, Asuzu Isaac

2013-01-01

28

Effect of ethanolic extract of Cassia occidentalis Linn. for the management of alloxan-induced diabetic rats  

PubMed Central

Aim: As per traditional claims, root, bark, leaf and flower of the plant Cassia occidentalis Linn. (Caesalpiniaceae) have been reported to possess antidiabetic activity. Based on this traditional indication, the aim of this study was to evaluate the antidiabetic activity of ethanolic extract of C. occidentalis in normal and alloxan induced diabetic rats. Materials and Methods: Ethanolic extract of the whole plant of C. occidentalis was orally tested at doses of 100 and 200 mg/kg for evaluating the hypoglycemic effect in normal and alloxan-induced diabetic rats. In addition, changes in body weight, serum cholesterol, triglyceride and total protein levels, assessed in the ethanol extract treated diabetic rats were compared with diabetic control and normal animals. Histopathologic observations during 21 days of treatment were also evaluated. Results: Ethanolic extract of C. occidentalis produced a significant reduction in fasting blood glucose levels in the normal and alloxan-induced diabetic rats at doses of 100 and 200 mg/kg body weight. Treatment with ethanolic extract of C. occidentalis in normal and alloxan-induced diabetic rats led to a dose-dependent fall in blood sugar levels. Significant differences were observed in serum lipid profiles (cholesterol and triglyceride), serum protein and changes in body weight in ethanolic extract treated diabetic animals, when compared with the diabetic control and normal animals. Concurrent histopathologic studies of the pancreas of these animals showed comparable regeneration by ethanolic extract, which were earlier necrosed by alloxan. Conclusion: Ethanolic extract of C. occidentalis exhibited significant antidiabetic activity in normal and alloxan-induced diabetic rats. The rats also showed improvement in parameters like body weight and lipid profiles and also, histopathologic studies showed regeneration of ?-cells of pancreas and so it might be of value in the treatment of diabetes. PMID:21808555

Verma, Laxmi; Singour, P. K.; Chaurasiya, P. K.; Rajak, H.; Pawar, R. S.; Patil, U. K.

2010-01-01

29

Protective effects of taurine against alloxan-induced diabetic cataracts and refraction changes in New Zealand White rabbits.  

PubMed

The present study examined the protective effects of taurine on alloxan-induced diabetic cataracts and lens damage in male New Zealand White rabbits. The animals were randomly divided into three treatment groups: (1) normal control (vehicle administration); (2) diabetes (100 mg/kg alloxan administration); and (3) diabetes + taurine (1% [w/v] taurine dissolved in drinking water and alloxan administration). The results showed that alloxan-induced diabetes caused significant (p < 0.05) hyperglycemia, hyperopic refraction shifts, cataract formation and lens damage compared with the normal control group. In contrast, the administration of taurine for 24 weeks significantly ameliorated the alloxan-induced elevated levels of blood glucose, level of hyperopic refraction error shifts in the eyes and progression of diabetic cataract formation in the lens in rabbits. Moreover, histopathology showed that the taurine supplement reduced the incidence of lens lesions induced by hyperglycemia. Overall, the studies demonstrate that taurine exhibits potent protective effects against alloxan-induced diabetic cataracts and refraction changes in rabbits. PMID:22940558

Hsu, Yu-Wen; Yeh, Shang-Min; Chen, Ya-Yu; Chen, Yi-Chen; Lin, Shiun-Long; Tseng, Jung-Kai

2012-10-01

30

Study of antihyperglycaemic activity of medicinal plant extracts in alloxan induced diabetic rats  

PubMed Central

Background: Diabetes mellitus, for a long time, has been treated with plant derived medicines in Sri Lanka. Aim: The aim of this study is to determine the efficacy and dose response of oral antihyperglycaemic activity of eight Sri Lankan medicinal plant extracts, which are used to treat diabetes in traditional medicine in diabetic rats. Materials and Methods: Medicinal plants selected for the study on the basis of documented effectiveness and wide use among traditional Ayurveda physicians in the Southern region of Sri Lanka for the treatment of diabetes mellitus. The effect of different doses of aqueous stem bark extracts of Spondias pinnata (Anacardiaceae), Kokoona zeylanica (Celastraceae), Syzygium caryophyllatum (Myrtaceae), Gmelina arborea (Verbenaceae), aerial part extracts of Scoparia dulcis (Scrophulariaceae), Sida alnifolia (Malvaceae), leaf extract of Coccinia grandis (Cucurbitaceae) and root extract of Languas galanga (Zingiberaceae) on oral glucose tolerance test was evaluated. A single dose of 0.25, 0.50, 0.75, 1.00, 1.25, 2.00 g/kg of plant extract was administered orally to alloxan induced (150 mg/kg, ip) diabetic Wistar rats (n = 6). Glibenclamide (0.50 mg/kg) was used as the standard drug. The acute effect was evaluated over a 4 h period using area under the oral glucose tolerance curve. Statistical Analysis: The results were evaluated by analysis of variance followed by Dunnett's test. Results: The eight plant extracts showed statistically significant dose dependent improvement on glucose tolerance (P < 0.05). The optimum effective dose on glucose tolerance for six extracts was found to be 1.00 g/kg in diabetic rats with the exception of C. grandis: 0.75 g/kg and L. galanga: 1.25 g/kg. Conclusion: The aqueous extract of G. arborea, S. pinnata, K. zeylanica, S. caryophyllatum, S. dulcis, S. alnifolia, L. galanga and C. grandis possess potent acute antihyperglycaemic activity in alloxan induced diabetic rats. PMID:24991066

Attanayake, Anoja P.; Jayatilaka, Kamani A. P. W.; Pathirana, Chitra; Mudduwa, Lakmini K. B.

2013-01-01

31

Effect of Aegle marmelos (L.) Correa on alloxan induced early stage diabetic nephropathy in rats.  

PubMed

Diabetic nephropathy (DN) has a complex pathogenesis and poor prognosis due to the lack of therapeutic interventions. The present study investigates the effect of A. marmelos leaf extract (AME) on early alloxan induced DN. The treatment with AME was found to significantly decrease the fasting blood sugar, total cholesterol, blood urea, creatinine and renal TBARS and increased the levels of renal reduced glutathione and catalase significantly as compared to the diabetic control group. The maximum dose-dependent protection was observed at a dose of 200 mg kg(-1). Histological examination revealed marked reversal of the morphological derangements with AME treatment as indicated by a decrease in glomerular expansion, tubular dilatation and inflammatory cells. The present results conclude that AME treatment has a significant ameliorative effect on early changes induced in the kidneys by alloxan and improves the outcome of DN. PMID:23926695

Bhatti, Rajbir; Sharma, Shikha; Singh, Jatinder; Singh, Amarjit; Ishar, M P S

2013-06-01

32

Antidiabetic activity of Pongamia pinnata leaf extracts in alloxan-induced diabetic rats  

PubMed Central

The antidiabetic activity of Pongamia pinnata ( Family: Leguminosae) leaf extracts was investigated in alloxan-induced diabetic albino rats. A comparison was made between the action of different extracts of P. pinnata and a known antidiabetic drug glibenclamide (600 ?g/kg b. wt.). An oral glucose tolerance test (OGTT) was also performed in experimental diabetic rats. The petroleum ether, chloroform, alcohol and aqueous extracts of P. pinnata were obtained by simple maceration method and were subjected to standardization using pharmacognostical and phytochemical screening methods. Dose selection was made on the basis of acute oral toxicity study (50-5000 mg/kg b. w.) as per OECD guidelines. P. pinnata ethanolic extract (PPEE) and aqueous extract (PPAE) showed significant (P < 0.001) antidiabetic activity. In alloxan-induced model, blood glucose levels of these extracts on 7th day of the study were 155.83 ± 11.211mg/dl (PPEE) and 132.00 ± 4.955mg/dl (PPAE) in comparison of diabetic control (413.50 ± 4.752mg/dl) and chloroform extract (210.83 ± 14.912mg/dl). In glucose loaded rats, PPEE exhibited glucose level of 164.50 ± 6.350mg/dl after 30 min and 156.50 ± 4.089mg/dl after 90 min, whereas the levels in PPAE treated animals were 176 ± 3.724mg/dl after 30 min and 110.33 ± 6.687mg/dl after 90 min. These extracts also prevented body weight loss in diabetic rats. The drug has the potential to act as an antidiabetic drug. PMID:21455444

Sikarwar, Mukesh S.; Patil, M.B.

2010-01-01

33

Antidiabetic activity of Pongamia pinnata leaf extracts in alloxan-induced diabetic rats.  

PubMed

The antidiabetic activity of Pongamia pinnata ( Family: Leguminosae) leaf extracts was investigated in alloxan-induced diabetic albino rats. A comparison was made between the action of different extracts of P. pinnata and a known antidiabetic drug glibenclamide (600 ?g/kg b. wt.). An oral glucose tolerance test (OGTT) was also performed in experimental diabetic rats. The petroleum ether, chloroform, alcohol and aqueous extracts of P. pinnata were obtained by simple maceration method and were subjected to standardization using pharmacognostical and phytochemical screening methods. Dose selection was made on the basis of acute oral toxicity study (50-5000 mg/kg b. w.) as per OECD guidelines. P. pinnata ethanolic extract (PPEE) and aqueous extract (PPAE) showed significant (P < 0.001) antidiabetic activity. In alloxan-induced model, blood glucose levels of these extracts on 7th day of the study were 155.83 ± 11.211mg/dl (PPEE) and 132.00 ± 4.955mg/dl (PPAE) in comparison of diabetic control (413.50 ± 4.752mg/dl) and chloroform extract (210.83 ± 14.912mg/dl). In glucose loaded rats, PPEE exhibited glucose level of 164.50 ± 6.350mg/dl after 30 min and 156.50 ± 4.089mg/dl after 90 min, whereas the levels in PPAE treated animals were 176 ± 3.724mg/dl after 30 min and 110.33 ± 6.687mg/dl after 90 min. These extracts also prevented body weight loss in diabetic rats. The drug has the potential to act as an antidiabetic drug. PMID:21455444

Sikarwar, Mukesh S; Patil, M B

2010-10-01

34

Modification of oxidative stress by pioglitazone in the heart of alloxan-induced diabetic rabbits.  

PubMed

The study was undertaken to analyze the effect of pioglitazone on superoxide dismutase (Cu, Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glutathione (GSH), ascorbic acid (AA), lipid peroxidation products (LPO) and protein carbonyl groups (PCG) in the heart of alloxan-induced diabetic rabbits after 4 and 8 weeks of pioglitazone treatment. In diabetic animals, Cu, Zn-SOD and CAT were elevated by 60 and 55%, and 90 and 77% as compared to controls at 4 and 8 weeks, respectively. GSH-Px, GSSG-R and GSH were diminished by 11, 14 and 33% as compared to controls at 4 or 8 weeks. AA was diminished by 52 and 41%. At P <0.05, pioglitazone normalized the activities of Cu, Zn-SOD, GSH-Px and GSSG-R. The activity of CAT was modified as compared to diabetic non-treated rabbits. After pioglitazone treatment, GSH and AA were increased as compared to diabetic non-treated animals. In diabetic rabbits, LPO was elevated by 52 and 111% and normalized by pioglitazone treatment. PCG was elevated by 72 and 133% and diminished as compared to diabetic non-treated animals at 8 weeks. The study shows that pioglitazone reduces oxidative stress in the heart of diabetic rabbits. In therapy, similar action can improve the cardiovascular system of diabetic patients. PMID:15959628

Gumieniczek, Anna

2005-01-01

35

Effect of atorvastatin and hydroxychloroquine combination on blood glucose in alloxan-induced diabetic rats  

PubMed Central

Objective: To evaluate the antihyperglycemic activity of atorvastatin and hydroxychloroquine combination in alloxan-induced diabetic rats. Materials and Methods: Alloxan induced diabetic Wistar male rats were randomized into six groups of 6 rats each. (Normal rats, diabetic control, atorvastatin (ATV), hydroxychloroquine (HCQ), ATV 5 mg /kg + HCQ 100 mg/kg, and ATV 10 mg/kg + HCQ 200 mg/kg). The rats were treated for 9 days and blood samples were collected at baseline and end of therapy. These samples were analyzed for plasma glucose by autoanalyzer. Changes in body weight, water, food intakes and total protein content were also recorded. Results: Atorvastatin and hydroxychloroquine alone and in combination reported significant fall in blood glucose level from baseline. Fall in glucose level was significantly more in high dose combination of atorvastatin and hydroxychloroquine (ATV: 10 mg/kg + HCQ: 200 mg/kg) as compared to other study treatment groups (ATV: 17% Vs HCQ: 7% Vs ATV 5mg/kg + HCQ 100mg /kg: 14% Vs ATV 10mg/kg + HCQ 200mg /kg: 21%; p<0.01). ATV and HCQ individually and in combination also improved the body weight loss. The weight gain was significantly more in combination treated rats as compared to positive control group and greater than those who received atorvastatin and hydroxychloroquine alone. Rats treated with the combination also reported significant decrease in food intake and significant increase in total protein. Conclusion: Increased hypoglycemic effect in combination may be due to potentiation or synergism between HCQ and ATV. Further studies are required to demonstrate clinically significant antidiabetic effect. PMID:20442820

Pareek, Anil; Yeole, P.G.; Tenpe, C.R.; Chandurkar, Nitin; Payghan, Ravikiran

2009-01-01

36

Amelioration of oxidative stress by Tabernamontana divaricata on alloxan-induced diabetic rats  

PubMed Central

Objective: The purpose of this study was to evaluate the anti-diabetic activity of ethanol extract of Tabernamontana divaricata (L.) and its ameliorative effect on oxidative stress in alloxan-induced diabetic rats. Materials and Methods: Diabetes was induced by single intraperitoneal injection of alloxan monohydrate (140 mg/kg body weight). Methanol extract of T. divaricata was administered at the doses of 100 and 200 mg/kg body weight in diabetic induced rats including glibenclamide (3 mg/kg) as a reference drug. In the continuous 21 days treatment, fasting blood glucose level was determined on 0, 7, 14 and 21 days. On day 21, serum lipid profiles and glycosylated hemoglobin, liver antioxidant enzymes levels were estimated. Results: Experimental findings showed a significant anti-diabetic potential of the extract in terms of reduction in blood glucose levels and a correct effect on the altered biochemical parameters. Observed data were found statistically significant in correction of antioxidant enzyme level accompanied with diabetes, particularly at the dose of 200 mg/kg body weight. Conclusion: Based on the results, it can be concluded that the T. divaricata is found to be effective in type 2 diabetes in rats and to have an ameliorative effect on the associated oxidative stress. PMID:25593402

Kanthlal, S. K.; Kumar, B. Anil; Joseph, Jipnomon; Aravind, R.; Frank, P. Royal

2014-01-01

37

Antioxidant, Antihyperlipidaemic and Antidiabetic Activity of Eugenia Floccosa Bedd Leaves in Alloxan Induced Diabetic Rats  

PubMed Central

The ethanol extract of Eugenia floccosa Bedd (Family: Myrtaceae) leaf was investigated for its antioxidant, antihyperlipidaemic and antidiabetic effect in Wistar Albino rats. Diabetes was induced in Albino rats by administration of alloxan monohydrate (150mg/kg, i.p). The ethanol extracts of E. floccosa at a dose of 150 and 300mg/kg of body weight were administered at single dose per day to diabetes induced rats for a period of 14 days. The effect of ethanol extract of E. floccosa leaf extract on blood glucose, plasma insulin, creatinine, glycosylated haemoglobin, urea serum lipid profile [total cholesterol (TR), triglycerides (TG), low density lipoprotein – cholesterol (LDL-C), very low density lipoprotein – cholesterol (VLDL-C), high density lipoprotein – cholesterol (HDL-C) and phospholipid (PL)] serum protein, albumin, globulin, serum enzymes [serum glutamate pyruvate transaminases (SGPT) and serum glutamate oxaloacetate transaminases (SGOT), and alkaline phosphatase (ALP)], lipoprotein peroxidation (LPO) antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GPx) were measured in the diabetic rats. The ethanol extract of Eugenia floccosa leaf elicited significant reductions of blood glucose (P<0.05), lipid parameters except HDL-C, serum enzymes and significantly increased HDL-C and antioxidant enzymes. The extracts also caused significant increase in plasma insulin (P<0.05) in the diabetic rats. From the above results, it is concluded that ethanol extract of Eugenia floccosa possesses significant antidiabetic, antihyperlipidaemic and antioxidant effects in alloxan induced diabetic rats. PMID:24826030

Jelastin, Kala S Mary; Tresina, P.S.; Mohan, V.R.

2011-01-01

38

Blood glucose lowering activity of aloe based composition, UP780, in alloxan induced insulin dependent mouse diabetes model  

PubMed Central

Background There are a few nutritional approaches to address the increased needs of managing diabetic conditions. Previously it has been reported that UP780, a standardized composition of aloe chromone formulated with an aloe polysaccharide, has a significant impact in reducing HbA1C, fasting blood glucose, fructosamine and plasma insulin level in humans and improved impaired glucose and insulin resistance in high-fat diet-induced and db/db non-insulin dependent diabetic mouse models. Here we describe activity of UP780 and its constituents to improve insulin sensitivity in alloxan induced insulin dependent diabetic mouse model. Materials and method Insulin dependent diabetes was induced by administering a single intraperitoneal injection of alloxan monohydrate at a dose of 150 mg/kg to CD-1 mice. Aloesin (UP394) was formulated with an Aloe vera inner leaf gel powder polysaccharide (Qmatrix) to yield a composition designated UP780. Efficacy of oral administration of UP780 at 2000 mg/kg and its constituents (aloesin at 80 mg/kg and Qmatrix at 1920 mg/kg) were evaluated in this model. Glyburide, a sulfonylurea drug used in the treatment of type 2 diabetes, was used at 5 mg/kg as a positive control. Effect of UP780 on non-diabetic normal mice was also addressed. Results Mice administered intraperitoneal alloxan monohydrate developed progressive type-1 diabetes like symptom. After 4 weeks of daily oral administration, reductions of 35.9%, 17.2% and 11.6% in fasting blood glucose levels were observed for UP780, the UP780 Aloe vera inner leaf gel polysaccharide preparation without chromone (Qmatrix), and Aloesin (UP394), treated animals respectively, compared to vehicle treated animals. UP780 has no impact on blood glucose level of non-diabetic healthy mice. UP780 showed statistically significant improvement for blood glucose clearance in oral glucose tolerance tests. Similarly, enhanced improvement in plasma insulin level and statistically significant reduction in triglyceride level was also observed for animals treated with the composition. Conclusion These findings suggest that UP780, a chromone standardized Aloe based composition, could possibly be used as a natural supplement alternative to facilitate maintenance of healthy blood glucose levels. PMID:24891878

2014-01-01

39

Hypoglycaemic and Hypolipidaemic Effects of Withania somnifera Root and Leaf Extracts on Alloxan-Induced Diabetic Rats  

PubMed Central

Withania somnifera is an important medicinal plant, which is used in traditional medicine to cure many diseases. Flavonoids were determined in the extracts of W. somnifera root (WSREt) and leaf (WSLEt). The amounts of total flavonoids found in WSREt and WSLEt were 530 and 520 mg/100 g dry weight (DW), respectively. Hypoglycaemic and hypolipidaemic effects of WSREt and WSLEt were also investigated in alloxan-induced diabetic rats. WSREt and WSLEt and the standard drug glibenclamide were orally administered daily to diabetic rats for eight weeks. After the treatment period, urine sugar, blood glucose, haemoglobin (Hb), glycosylated haemoglobin (HbA1C), liver glycogen, serum and tissues lipids, serum and tissues proteins, liver glucose-6-phosphatase (G6P) and serum enzymes like aspartate transaminase (AST), alanine transaminase (ALT), acid phosphatase (ACP) and alkaline phosphatase (ALP) levels were determined. The levels of urine sugar, blood glucose, HbA1C, G6P, AST, ALT, ACP, ALP, serum lipids except high density lipoprotein-bound cholesterol (HDL-c) and tissues like liver, kidney and heart lipids were significantly (p < 0.05) increased, however Hb, total protein, albumin, albumin:globulin (A:G) ratio, tissues protein and glycogen were significantly (p < 0.05) decreased in alloxan-induced diabetic rats. Treatment of the diabetic rats with WSREt, WSLEt and glibenclamide restored the changes of the above parameters to their normal level after eight weeks of treatment, indicating that WSREt and WSLEt possess hypoglycaemic and hypolipidaemic activities in alloxan-induced diabetes mellitus (DM) rats. PMID:19564954

Udayakumar, Rajangam; Kasthurirengan, Sampath; Mariashibu, Thankaraj Salammal; Rajesh, Manoharan; Anbazhagan, Vasudevan Ramesh; Kim, Sei Chang; Ganapathi, Andy; Choi, Chang Won

2009-01-01

40

Beneficial Effects of Pentanema vestitum Linn. Whole Plant on the Glucose and Other Biochemical Parameters of Alloxan Induced Diabetic Rabbits.  

PubMed

The residents of Lower Dir and Malakand agency, Khyber Pakhtunkhwa, Pakistan, use the dry powder of whole plant of Pentanema vestitum for the treatment of asthma and diabetes. No documented reports are available about the therapeutic action of Pentanema vestitum. The present study was aimed to explore the antihyperglycemic effect of 70% methanol extract of Pentanema vestitum whole plant in glucose-induced nondiabetic hyperglycemic and alloxan-induced diabetic rabbits. During this study, the effects of plant extract on the serum lipid profile, GPT, ALP, bilirubin and creatinine of diabetic rabbits were also studied. The extract of Pentanema vestitum whole plant exhibited significant (P < 0.05) antihyperglycemic activity in glucose-induced hyperglycemic rabbits. Treatment of alloxan-induced diabetic rabbits with extract significantly (P < 0.05) reduced the elevated levels of serum glucose, GPT, ALP, bilirubin and creatinine. During the study of lipid profile, the extract proved to be antihyperlipidemic and HDL boosting in diabetic rabbit models. From the finding of the present research, it was concluded that the 70% methanol extract of Pentanema vestitum whole plant has beneficial effects on serum levels of glucose, lipid profile, GPT, ALP, bilirubin, and creatinine of diabetic rabbits. PMID:23316385

Ilahi, Ikram; Asghar, Ali; Ali, Shujat; Khan, Murad; Khan, Nasrullah

2012-01-01

41

Beneficial Effects of Pentanema vestitum Linn. Whole Plant on the Glucose and Other Biochemical Parameters of Alloxan Induced Diabetic Rabbits  

PubMed Central

The residents of Lower Dir and Malakand agency, Khyber Pakhtunkhwa, Pakistan, use the dry powder of whole plant of Pentanema vestitum for the treatment of asthma and diabetes. No documented reports are available about the therapeutic action of Pentanema vestitum. The present study was aimed to explore the antihyperglycemic effect of 70% methanol extract of Pentanema vestitum whole plant in glucose-induced nondiabetic hyperglycemic and alloxan-induced diabetic rabbits. During this study, the effects of plant extract on the serum lipid profile, GPT, ALP, bilirubin and creatinine of diabetic rabbits were also studied. The extract of Pentanema vestitum whole plant exhibited significant (P < 0.05) antihyperglycemic activity in glucose-induced hyperglycemic rabbits. Treatment of alloxan-induced diabetic rabbits with extract significantly (P < 0.05) reduced the elevated levels of serum glucose, GPT, ALP, bilirubin and creatinine. During the study of lipid profile, the extract proved to be antihyperlipidemic and HDL boosting in diabetic rabbit models. From the finding of the present research, it was concluded that the 70% methanol extract of Pentanema vestitum whole plant has beneficial effects on serum levels of glucose, lipid profile, GPT, ALP, bilirubin, and creatinine of diabetic rabbits. PMID:23316385

Ilahi, Ikram; Asghar, Ali; Ali, Shujat; Khan, Murad; Khan, Nasrullah

2012-01-01

42

Effects of chronic diabetes on vascular responses of basilar artery and aorta from rabbits with alloxan-induced diabetes.  

PubMed

The influences of chronically diabetic states on contraction and relaxation responses of the isolated basilar artery and aorta to various vasoactive agents were examined in alloxan-induced diabetic rabbits with 2 years duration. There were no significant differences in the reactivities of basilar artery to norepinephrine (NE), 5-hydroxytryptamine (5-HT) and KCl between age-matched control and diabetic rabbits. Maximal contractions of aorta with endothelium in response to NE and 5-HT were significantly enhanced in case concentration-response curves for NE and 5-HT-induced contractions in the aorta without endothelium from diabetic rabbits were not different from those from age-matched control rabbits. Acetylcholine-induced relaxations in both the basilar artery and aorta from diabetic rabbits were significantly attenuated compared with those from age-matched control rabbits. However, no differences were observed in concentration-response curves for sodiumnitroprusside-induced relaxations in both the basilar artery and aorta between diabetic rabbits and age-matched control rabbits. These results indicate that chronic diabetes induces an specific enhancement in the contractile responses to NE and 5-HT in aorta and an attenuation in the endothelium-dependent relaxation in both the basilar artery and aorta. These results further demonstrated that the cerebral artery is resistant to diabetes of 2 years duration as compared with the peripheral artery. PMID:1801104

Abiru, T; Kamata, K; Kasuya, Y

1991-10-01

43

Serum Glucose and Malondialdehyde Levels in Alloxan Induced Diabetic Rats Supplemented with Methanolic Extract of Tacazzea Apiculata  

PubMed Central

Tacazzea apiculata is used by traditional medical practitioners for the treatment of wide range of diseases. The current work investigated the hypoglycemic and antioxidant properties of Tacazzea apiculata Oliv. on alloxan induced diabetes mellitus. Five groups (n=10) of rats were fed on commercial diet. The rats were divided into Group 1 (NUT) as non-diabetic and untreated, group 2 (NDT) as non-diabetic and treated, group 3 (DT) diabetic and treated. Group 4 (DUT) as diabetic and untreated. Group five (CP) were diabetic treated with Chlorpropamide, a drug used in the management of diabetic mellitus, with no known antioxidant property. Diabetic induction was done by intra-peritoneal injection of 100 mg/kg b. wt with alloxan. Fasting blood glucose was estimated seven days after induction to determine the severity of glucose elevation among the induced groups. Methanolic extract of T. apiculata leaf was administered to alloxan induced diabetic and non-diabetic control rats at 100mg/kg body weight for four weeks and blood glucose estimated on weekly basis. Malondialdehyde level was also estimated in the sera of the rats. Blood glucose level was monitored for additional 2 weeks post treatment. The results indicated that the extracts possess significant hypoglycemic effect on the diabetic rats (DT) having the mean glucose of (95.2 ± 9.12 mg/dl) compared to the diabetic untreated control group (DUT) with a mean glucose of (238.91 ± 4.42 mg/dl, p<0.05). The effect was sustained even on withdrawal of the extracts for two weeks. This was accompanied by a progressive increase in weight among all treated diabetic rats and non diabetic treated (DT and NDT) compared with diabetic untreated control rat (DUT) (p<0.05). A raised level in malondialdehyde was also observed among the diabetic rat prior to treatment and significantly decreased after the treatment. In conclusion the research demonstrated the hypoglycaemic and antioxidant potential of methanolic leaf extract of T. apiculata in alloxan induced rats. PMID:25598753

Gwarzo, M. Y.; Ahmadu, J. H.; Ahmad, M. B.; Dikko, A. U. A.

2014-01-01

44

Serum glucose and malondialdehyde levels in alloxan induced diabetic rats supplemented with methanolic extract of tacazzea apiculata.  

PubMed

Tacazzea apiculata is used by traditional medical practitioners for the treatment of wide range of diseases. The current work investigated the hypoglycemic and antioxidant properties of Tacazzea apiculata Oliv. on alloxan induced diabetes mellitus. Five groups (n=10) of rats were fed on commercial diet. The rats were divided into Group 1 (NUT) as non-diabetic and untreated, group 2 (NDT) as non-diabetic and treated, group 3 (DT) diabetic and treated. Group 4 (DUT) as diabetic and untreated. Group five (CP) were diabetic treated with Chlorpropamide, a drug used in the management of diabetic mellitus, with no known antioxidant property. Diabetic induction was done by intra-peritoneal injection of 100 mg/kg b. wt with alloxan. Fasting blood glucose was estimated seven days after induction to determine the severity of glucose elevation among the induced groups. Methanolic extract of T. apiculata leaf was administered to alloxan induced diabetic and non-diabetic control rats at 100mg/kg body weight for four weeks and blood glucose estimated on weekly basis. Malondialdehyde level was also estimated in the sera of the rats. Blood glucose level was monitored for additional 2 weeks post treatment. The results indicated that the extracts possess significant hypoglycemic effect on the diabetic rats (DT) having the mean glucose of (95.2 ± 9.12 mg/dl) compared to the diabetic untreated control group (DUT) with a mean glucose of (238.91 ± 4.42 mg/dl, p<0.05). The effect was sustained even on withdrawal of the extracts for two weeks. This was accompanied by a progressive increase in weight among all treated diabetic rats and non diabetic treated (DT and NDT) compared with diabetic untreated control rat (DUT) (p<0.05). A raised level in malondialdehyde was also observed among the diabetic rat prior to treatment and significantly decreased after the treatment. In conclusion the research demonstrated the hypoglycaemic and antioxidant potential of methanolic leaf extract of T. apiculata in alloxan induced rats. PMID:25598753

Gwarzo, M Y; Ahmadu, J H; Ahmad, M B; Dikko, A U A

2014-12-01

45

Hypoglycemic and hypolipidemic activity of ethanolic extract of Salvadora oleoides in normal and alloxan-induced diabetic rats  

PubMed Central

Objective: To find out the hypoglycemic and hypolipidemic activity of an ethanolic extract of the aerial part of Salvadora oleoides Decne in euglycemic and alloxan-induced diabetic albino rats. Materials and Methods: Diabetes was induced in albino rats by administration of alloxan monohydrate (120 mg/kg, i.p.). Normal as well as diabetic albino rats were divided into groups (n = 6) receiving different treatments: vehicle (control), ethanolic extract (1 g and 2 g/kg b.w), and standard antidiabetic drug tolbutamide (0.5 g/kg b.w.). Blood samples were collected by cardiac puncture and were analyzed for blood glucose and lipid profile on days 0, 7, 14, and 21. Results: The ethanolic extract of S oleoides produced significant reduction (P < 0.001) in blood glucose and also had beneficial effects (P < 0.001) on the lipid profile in euglycemic as well as alloxan-induced diabetic rats at the end of the treatment period (21st day). However, the reduction in the blood glucose and improvement in lipid profile was less than that achieved with the standard drug tolbutamide. Conclusion: We concluded that an ethanolic extract of S oleoides is effective in controlling blood glucose levels and improves lipid profile in euglycemic as well as diabetic rats. PMID:21264157

Yadav, J.P.; Saini, Sushila; Kalia, A.N.; Dangi, A.S.

2008-01-01

46

Hepatoprotective and Hypolipidemic Effects of Satureja Khuzestanica Essential Oil in Alloxan-induced Type 1 Diabetic Rats  

PubMed Central

In the present study, we examined the antioxidative activities of Satureja khuzestanica essential oil (SKE) and possible protective effect of SKE on lipid profile, atherogenic index and liver enzyme markers in Alloxan-induced Type 1 diabetic rats. Thirty male rats were randomly divided into three groups; group one as control, group two diabetic untreatment, and group three treatments with SKE by 500 ppm in drinking water, respectively. Diabetes was induced in the second and third groups by alloxan injection subcutaneously. After 8 weeks, the levels of fasting blood glucose (FBG), triglyceride (TG), cholesterol (C), low density lipoprotein (LDL), very low density lipoprotein (VLDL), high density lipoprotein (HDL), atherogenic index and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) of all groups were analyzed. Data were analyzed through non-parametric Man Whitney test (using SPSS 13 software) and p < 0.05 was considered significant. SKE inhibited significantly the activities of ALT and ALP and decrease FBG, TG, C, LDL and VLDL. HDL level was significantly increased when treated with the extract. The activities of AST stayed unaltered. Moreover, total antioxidant capacity of SKE was 3.20 ± 0.40 nmol of ascorbic acid equivalents/g SKE. This study showed that SKE is a source of potent antioxidants. The findings of the present study also suggest that SKE exert beneficial effects on the lipid profile, atherogenic index and liver enzymes activity in Alloxan-induced Type 1 diabetic rats. PMID:24250556

Ahmadvand, Hassan; Tavafi, Majid; Khalatbary, Ali Reza

2012-01-01

47

Mitigating effects of antioxidant properties of Artemisia campestris leaf extract on hyperlipidemia, advanced glycation end products and oxidative stress in alloxan-induced diabetic rats  

Microsoft Academic Search

Artemisia campestris is used as antivenom and anti-inflammatory Tunisian folk medicine. Recently, increased oxidative stress was shown to play an important role in the etiology and pathogenesis of diabetes mellitus and its complications. This study was designed to examine the effects of A. campestris leaf aqueous extract (Ac) on alloxan-induced diabetic rats by measuring glycemia, lipid profile, lipid peroxidation (MDA),

Mediha Sefi; Hamadi Fetoui; Mohamed Makni; Najiba Zeghal

2010-01-01

48

Antihyperglycemic and hypolipidemic effects of Helicteres isora roots in alloxan-induced diabetic rats: a possible mechanism of action.  

PubMed

The antihyperglycemic and hypolipidemic activities of Helicteres isora Linn. (Sterculiaceae) root extracts were investigated in alloxan-induced diabetic rats and a possible mechanism of the blood glucose lowering action was studied. Alloxan-induced diabetic rats experienced 69.13 and 51.14%, 22.60 and 21.89%, 30.12 and 19.96%, and 50.05 and 34.29% reduction in blood glucose, total cholesterol, triglycerides, and urea levels following oral administration of butanol and aqueous ethanol extracts of H. isora root, respectively, at 250 mg/kg for 10 days. The beneficial effects of these extracts were supported by evidence from histological examinations of the liver, pancreas, and kidney. Following the treatment with both extracts, the degenerative changes caused by alloxan in pancreatic cells were restored, particularly with the butanol extract. Histological examination convincingly showed the restoration of pancreatic islets, kidney glomeruli, and liver to its normal size. These results suggest that H. isora roots possess antidiabetic principles and can be useful for treatment of diabetes. PMID:20238178

Venkatesh, Sama; Madhava Reddy, B; Dayanand Reddy, G; Mullangi, Ramesh; Lakshman, M

2010-07-01

49

Therapeutic potency of saponin rich aqueous extract of Scoparia dulcis L. in alloxan induced diabetes in rats  

PubMed Central

Background: Diabetes mellitus is major metabolic disorders of carbohydrate metabolism. This leads to alter the multiple organ system. Aims: To investigate the antidiabetic and antioxidant effects of the saponin rich aqueous extract of Scoparia dulcis (SRE-SD) using alloxan-induced hyperglycemic rat model. Material and Methods: The single dose of alloxan was injected for the induction of diabetes in rats. The SRE-SD and glibenclamide were administered for 15 consecutive days from the 3rd day of alloxan administration. Quantity of food and water intake was measured at day 0, and 18. Further, body weight was recorded and blood samples were collected at different time intervals that is, day 0, 3, 8, 13, and 18. The oxidative biomarkers (i.e. thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and nitrite (NO2?) levels were also estimated in the serum sample. Results: The SRE-SD showed a remarkable dose and time-dependent changes in alloxan-induced rise in the level of food consumption and water intake, serum glucose level, TBARS, NO2? and fall in the level of GSH. Further, significant attenuation was observed at 20 and 30 mg/kg of SRE-SD treated group. Conclusions: These findings demonstrate that SRE-SD has both antidiabetic and antioxidant effects on the experimental model of diabetes in rat.

Perumal, P. Saravana; Anaswara, P. V.; Muthuraman, A.; Krishan, S.

2014-01-01

50

Antiatherogenic, hepatoprotective, and hypolipidemic effects of coenzyme Q10 in alloxan-induced type 1 diabetic rats  

PubMed Central

BACKGROUND Diabetes mellitus, one of the leading metabolic syndromes, accounts for highest morbidity and mortality worldwide. In this study, we examined possible protective effect of coenzyme Q10 on lipid profile, atherogenic index, and liver enzyme markers in alloxan-induced type 1 diabetic rats. METHODS A total of 30 male rats were randomly divided into three groups; group 1 as control, group 2 diabetic untreatment, and group 3 treatments with coenzyme Q10 by 15 mg/kg i.p. daily, respectively .Diabetes was induced in the second and third groups by alloxan injection subcutaneously. After 8 weeks, the levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), very low-density lipoprotein (VLDL), high density lipoprotein (HDL), atherogenic index, atherogenic coefficient, cardiac risk ratio, and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) of all groups were analyzed. Data were analyzed using non-parametric Mann-Whitney test (using SPSS) and P < 0.05 was considered as significant. RESULTS Coenzyme Q10 inhibited significantly the activities of ALT (11.17%), AST (19.35%) and ALP (36.67%) and decreased FBG (21.19%), TG (37.24%), TC (17.15%), LDL (30.44%), VLDL (37.24%), atherogenic index (44.24%), atherogenic coefficient (49.69%), and cardiac risk ratio (37.97%), HDL level was significantly (33.38%) increased when treated with coenzyme Q10. CONCLUSION The findings of this study suggest that coenzyme Q10 exert beneficial effects on the lipid profile, atherogenic index, and liver enzymes activity in alloxan-induced type 1 diabetic rats. PMID:25258634

Ahmadvand, Hassan; Ghasemi-Dehnoo, Maryam

2014-01-01

51

Liver-Protective Effects of Hydroalcoholic Extract of Allium Hirtifolium Boiss. in Rats with Alloxan-Induced Diabetes Mellitus  

PubMed Central

BACKGROUND Diabetes mellitus is one of the most common endocrine disorders accompanied with many metabolic syndromes. Use of herbal medicines has always been an option to treat a great number of diseases such as diabetes and its complications. In this study the liver-protective effects of hydroalcoholic extract of Allium hirtifolium on liver enzymes level in rats with alloxan-induced diabetes mellitus was investigated. METHODS Thirty five male rats were randomly divided into five groups of seven; group 1: nondiabetic control, group 2: diabetic control, group 3: diabetic treated with shallot extract (0.1 g/kg), group 4: diabetic rats treated with shallot extract (1 g/kg), and group 5: diabetic treated with glibenclamide (0.6 mg/kg). Using intraperitoneal (IP) injection of alloxan monohydrate, diabetes mellitus was induced in rats. Diabetic rats were treated with intraperitoneal injection for 4 weeks. At the end of the experimental period fasting blood samples were collected. RESULTS Statistical analysis of the data indicated that hydroalcoholic extract of shallot can significantly decrease serum contents of liver enzymes (ALP, AST, and ALT) in treated groups. In most cases, the effectiveness of the extract on reduction of these enzymes is more than glibenclamide. CONCLUSION Antioxidant compounds in the extract may recover liver damages caused by free radicals in diabetic rats. PMID:22577407

Kazemi, Somayeh; Asgary, Sedigheh; Moshtaghian, Jamal; Rafieian, Mahmoud; Adelnia, Azadeh; Shamsi, Fatemeh

2010-01-01

52

Antidiabetic and antihyperlipidaemic activity of ethanol extract of Melastoma malabathricum Linn. leaf in alloxan induced diabetic rats  

PubMed Central

Objective To evaluate the antidiabetic and antihyperlipidaemic effect of ethanol extract of Melastoma malabathricum (M. malabathricum) Linn. leaf in alloxan induced diabetic rats. Methods Diabetes was induced in albino rats by administration of alloxan monohydrate (150 mg/kg i.p). the ethanol extracts of M. malabathricum at a dose of 150 and 300 mg/kg of body weight were administrated at a single dose per day to diabetes induced rats for a period of 14 d. The effect of ethanol extract of M. malabathricum leaf extract on blood glucose, plasma insulin, creatinine, glycosylated haemoglobin, urea serum lipid profile [total cholesterol, triglycerides, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and phospholipid, serum protein, albumin, globulin, serum enzymes (serum glutamate pyruvate transaminases), serum glutamate oxaloacetate transaminases, and alkaline phosphatase] were measured in the diabetic rats. Results In the acute toxicity study, ethanol extract of M. malabathricum leaf was non-toxic at 2?000 mg/kg in rats. The increased body weight, decreased blood glucose, glycosylated haemoglobin and other biochemical parameters level were observed in diabetic rats treated with both doses of ethanol extract of M. malabathricum leaf compared to diabetic control rats. In diabetic rats, ethanol extract of M. malabathricum leaf administration, altered lipid profiles were reversed to near normal than diabetic control rats. Conclusions Ethanol extract of M. malabathricum leaf possesses significant antidiabetic and antihyperlipidaemic activity in diabetic rats. PMID:25183126

Balamurugan, Karuppasamy; Nishanthini, Antony; Mohan, Veerabahu Ramasamy

2014-01-01

53

Effect of Carthamus tinctorius (Safflower) on fasting blood glucose and insulin levels in alloxan induced diabetic rabbits.  

PubMed

Diabetes mellitus is a major threat to present and future generations. The role of herbal medication has emerged as a safe alternative to currently available medication due to its decreased potential to produce side effects, hence effect of Carthamus tinctorius was observed on fasting blood glucose and insulin levels in alloxan induced diabetic rabbits. Thirty five healthy male rabbits were divided into 5 groups with 7 rabbits in each (Normal control, diabetic control, diabetic treated with glibenclamide, diabetic treated with Carthamus tinctorius extract at doses of 200 and 300mg/kg of body weight). Drug and extract were given orally for 30 days and the values for blood glucose levels were observed after 15(th) and 30(th) day of treatment by using standard reagent kits provided by Human Germany. While insulin levels were checked at the end of the study by using Architect i1000 by Abbott Diagnostics USA. Animals were also observed for any gross toxicity during the study. Results revealed that Carthamus tinctorius has significant hypoglycemic effect at 200mg/kg and 300mg/kg doses as compared to diabetic control group. Insulin levels were significantly increased in Glibenclamide treated as well as Carthamus tinctorius treated groups as compared to diabetic control. PMID:24577929

Qazi, Nasreen; Khan, Rafeeq Alam; Rizwani, Ghazala H; Feroz, Zeeshan

2014-03-01

54

Anti-oxidant and anti-hyperglycemic activities of musa sapientum root extracts in alloxan-induced diabetic rats.  

PubMed

Anti-hyperglycemic and anti-oxidant properties of methanolic (MEMS) and aqueous (AEMS) extracts of Musa sapientum roots were investigated in alloxan-induced diabetic rats. Thirty adult male Wistar albino rats divided into five groups of 6 rats each were used: group 1--non-diabetic untreated (controls), group 2--diabetic untreated, and groups 3, 4 and 5--diabetic rats treated with 250 mg/kg bodyweight MEMS and AEMS, and 500 mg/kg bodyweight glibenclamide (a standard anti-diabetic drug), respectively. There was severe progressive weight loss in the untreated diabetic rats, while the rats in all the treated diabetic groups gained weight. While there was progressive hyperglycaemia in untreated diabetic rats; with blood glucose levels reaching a peak of 335.5 +/- 1.1 mg/dl on day 7 post-induction, compared to 76.8 +/- 0.8 mg/dl on day 0, these values were reduced to 80.7 +/- 0.5, 86.6 +/- 0.6 and 86.8 +/- 0.5 in MEMS, AEMS and glibenclamide-treated diabetic rats 15 days post-treatment. Also there were decreases in serum lipid peroxidation and increases in serum superoxide dismutase activities in MEMS, AEMS and glibenclamide-treated diabetic rats 15 days post-treatment. Lesions observed in the organs of untreated diabetic rats include selective necrosis of pancreatic beta islet cells, hepatocellular degeneration and necrosis, glomerulonephrosis and cardiovascular degeneration. Treatment of diabetic rats with AEMS and glibenclamide caused a total mitigation, while treatment with the MEMS achieved partial but considerable reduction in the severity of the lesions. It is concluded that aqueous and methanolic extracts of Musa sapientum roots possess anti-diabetic activities comparable to glibenclamide. PMID:20175413

Adewoye, E O; Taiwo, V O; Olayioye, F A

2009-06-01

55

Antihyperlipidemic effect of active principle isolated from seed of Eugenia jambolana on alloxan-induced diabetic rabbits.  

PubMed

Diabetes is accompanied by lipid abnormalities, which contribute significantly to cardiovascular morbidity and mortality in diabetic patients. We previously demonstrated the potent antihyperglycemic activity of the active principle (fraction II from Sephadex LH 20 chromatography [LH II]) isolated from ethanolic seed extract of Eugenia jambolana in diabetic rabbits. In the present study, the efficacy of LH II was evaluated for its hypolipidemic activity in alloxan-induced mildly diabetic (MD) and severely diabetic (SD) rabbits. Phytochemical investigation of LH II by various structural spectra showed the presence of saturated fatty acid, ?(5) lipid, and sterol. Oral administration of LH II (10?mg/kg of body weight) for 21 days resulted in improved glycemic control in both MD and SD rabbits. After treatment with LH II, serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, and the total cholesterol/high-density lipoprotein cholesterol ratio were significantly improved. LH II also resulted in significant (P?

Sharma, Suman B; Tanwar, Reenu S; Nasir, Afreena; Prabhu, Krishna M

2011-04-01

56

Effects of oropharyngeal/buccal insulin on glucose levels in alloxan-induced diabetic rabbits: clinical implications.  

PubMed

The effect of oropharyngeal administration of insulin lente (BP, USP) on alloxan-induced diabetic rabbits was investigated. In mild cases of hyperglycaemia (below 500 mg/dl), a buccal dose of 100 IU was able to produce significant reduction in blood glucose levels over seven hours, as compared with diabetic animals during the same period. As much as 60% reduction in glucose level from the starting level could be achieved. However, at very high levels of hyperglycaemia (above 500 mg/dl), this regimen failed to produce normoglycaemia although it rendered the animal tolerant to high levels of glucose. This mode of administration of insulin did not produce hypoglycaemia in any of the animals: the blood levels in the mildly diabetic animals were reduced to normoglycaemia without progressing into the hypoglycaemic state. The administration of insulin to normoglycaemic rabbits by this route did not produce any reduction in glucose levels. This preliminary report suggests that a noninvasive oropharyngeal route may be an alternative for the clinical management of insulin and non-insulin dependent diabetes mellitus in man. PMID:12153361

Koech, Davy K.; Kofi-Tsekpo, Mawuli W.

1994-05-01

57

Protective Effect of Lavandula stoechas and Rosmarinus officinalis Essential Oils Against Reproductive Damage and Oxidative Stress in Alloxan-Induced Diabetic Rats.  

PubMed

Abstract The authors aimed in the present study to assess the protective effect of Rosmarinus officinalis essential oils (ROEO) and Lavandula stoechas essential oils (LSEO) against reproductive damage and oxidative stress in alloxan-induced diabetic male rats. Essential oil samples were obtained from the aerial parts of the plants by hydrodistillation and analyzed by the gas chromatography-mass spectrometry (GC-MS). Rats were divided into four groups: healthy control (HC); diabetic control (DC); healthy+ROEO (H+ROEO), healthy+LSEO (H+LSEO), diabetic+ROEO (D+ROEO), and diabetic+LSEO (D+LSEO). The use of GC-MS allowed to the identification of 15 and 22 compounds in ROEO and LSEO, respectively. In addition, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test showed that ROEO and LSEO had an important antioxidant capacity. In vivo, we initially found that ROEO and LSEO treatment protected against the decrease in alloxan-induced body weight gain, relative reproductive organ weights, testosterone level, as well as sperm quality decline. On the other hand, we showed that alloxan administration was accompanied by an oxidative stress status assessed by an increase of malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels, as well as a depletion of sulfhydril group content (-SH) and antioxidant enzyme activities as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in testis, epididymis, and sperm. More importantly, ROEO and LSEO treatment significantly protected against oxidative damage of the male reproductive organ systems in alloxan-induced diabetic rats. These findings suggested that ROEO and LSEO exerted a potential protective effect against alloxan-induced reproductive function damage and oxidative stress in male rat. The beneficial effect of ROEO and LSEO might be related, in part, to their antioxidant properties. PMID:25105335

Sebai, Hichem; Selmi, Slimen; Rtibi, Kais; Gharbi, Najoua; Sakly, Mohsen

2014-08-01

58

Persistence of acidosis in alloxan-induced diabetic rats treated with the juice of Asystasia gangetica leaves  

PubMed Central

Background: Diabetes mellitus is gradually becoming a global health burden leading to an increase in the search for herbal hypoglycemic agents as alternatives to synthetic ones. Asystasia gangetica is one of the herbs used in folklore system of medicine for managing hypoglycaemia associated with diabetes. Materials and Methods: The influence of the juice of A. gangetica leaf on alloxan-induced diabetic rats was assessed by treating diabetic rats with 25%, 50% and 75% fresh juice and glibenclamide for 5 weeks. Afterwards, the plasma concentrations of glucose, triacylglycerols, total cholesterol, high-density lipoprotein (HDL) cholesterol, thiobarbituric acid reactive substances and bicarbonate were assayed spectrophotometrically. Results: Treatment of the diabetic rats with the juice significantly (P < 0.05) reduced the elevated plasma levels of glucose to a level not significantly (P > 0.05) different from that of glibenclamide. The juice also significantly (P < 0.05) reduced the plasma lipid peroxidation and improved the lipid profile, as indicated by a significant (P < 0.05) reduction in the total cholesterol: HDL cholesterol ratio. However, there was a significant (P < 0.05) rise in the level of bicarbonate as result of the juice treatment from 28.15 ± 2.82 mmol/l in normal control to 60.83 ± 17.46 mmol/l in diabetic control and to 122.20 ± 34.68 mmol/l, 120.95 ± 35.09 mmol/l and 115.85 ± 11.79 mmol/l in 25%, 50% and 75% juice, respectively. Conclusion: Therefore, this inability of A. gangetica to prevent acidosis detracts from the potential of its usefulness in managing diabetes. PMID:21472075

Rotimi, Solomon O.; Omotosho, Omolola E.; Rotimi, Oluwakemi A.

2011-01-01

59

The hypoglycemic effect of the aqueous extract of the fruits of Balanites aegypticea in Alloxan-induced diabetic rats  

PubMed Central

Background: Balanites aegypticea is used medically for many purposes e.g. anti-spasmodic, stomach pain, malaria, and yellow fever. The extract of the fruit is also used to reduce the blood glucose levels. Objectives: The objective of this study was to investigate the hypoglycemic effects of the aqueous extract of the fruits of the Balanites aegypticea in alloxan-induced diabetic rats. Materials and Methods: Twenty-five adult male Vistar rats were used in this study. The rats were randomly collected and divided into 5 groups (5 rats in each group). The untreated rats (negative control group) received basal diet and tap water only for 15 days. The experimental rats became diabetic by intraperitoneal injection of alloxan (150 mg/kg body weight). The fruit of Balanites aegypticea was powdered, extracted, and dried using organic solvents. The diabetic rats received aqueous extract 200 mg/kg, 400 mg/kg, and 800 mg/kg, respectively, for 2 weeks. Plasma glucose levels were measured by using Glucose GOD-PAP method through spectrophotometer. Results: The results showed that 800 mg/kg aqueous extract decrease significantly the plasma glucose level (P ? 0.05) in diabetic rats, and there is a considerable gain in body weight (P ? 0.05) compared to the diabetic control group. Four-hundred mg/kg aqueous extract has a mild effect on body weights and plasma glucose levels, while 200 mg/kg aqueous extract has no significant effect on plasma glucose level and a little effect on body weight. Conclusions: The results of the presented study revealed that the aqueous extract of Balanites aegypticea has hypoglycemic properties. It can decrease the plasma glucose level and can improve weight in diabetic experimental animals. PMID:24497735

Baragob, Abdella Emam Abdella; AlMalki, Waleed Hassan; Shahid, Imran; Bakhdhar, Fatimah Abdullah; Bafhaid, Hanouf Saeed; Eldeen, Omar Muhammad Izz

2014-01-01

60

Hypoglycaemic and hypolipidemic effect of ethanolic extract of seeds of Eugenia jambolana in alloxan-induced diabetic rabbits.  

PubMed

The hypoglycaemic and hypolipidemic effect of ethanolic extract obtained from seeds of E. jambolana was investigated in alloxan-induced diabetic rabbits. Hypoglycaemic activity was assessed by reduction in fasting blood glucose (FBG) at 90min and also fall in peak blood glucose during glucose tolerance test (GTT) in sub-diabetic and mild diabetic (MD) rabbits, but in severe diabetic (SD) rabbits by reduction in FBG at 90min. Ethanolic extract (100mg/kg body weight) when given orally to sub-diabetic (AR) for 1 day, MD for 7 days and SD for 15 days showed significant fall in FBG at 90min (12% AR, 18.9% MD and 29% SD) and also produced 16.9% fall in peak blood glucose in AR and 21% in MD rabbits during GTT. When administered daily for 15 days to MD and SD rabbits, significant fall in FBG (41.3% MD, 31.6% SD) and glycosylated haemoglobin (GHb) levels (23.3% MD, 26.6% SD) were observed, while serum insulin level showed significant increase (32.8% MD, 26.9% SD). Liver and muscle glycogen content also increased. The ethanolic extract of seeds also exhibited significant hypolipidemic effect as evident from fall in total serum cholesterol (TC)/high density lipoprotein cholesterol (HDL-c) ratio, serum low density lipoprotein cholesterol (LDL-c) levels and decreased activity of HMG-CoA reductase. The histopathological studies of liver, pancreas and aorta in alcoholic extract treated diabetic groups revealed almost normal appearance. PMID:12639741

Sharma, S B; Nasir, A; Prabhu, K M; Murthy, P S; Dev, G

2003-04-01

61

Lavender (Lavandula stoechas L.) essential oils attenuate hyperglycemia and protect against oxidative stress in alloxan-induced diabetic rats  

PubMed Central

Background The present study described the phytochemical profile of Lavandula stoechas essential oils, collected in the area of Ain-Draham (North-West of Tunisia), as well as their protective effects against alloxan-induced diabetes and oxidative stress in rat. Methods Essential oils samples were obtained from the aerial parts of the plant by hydrodistillation and analyzed by GC–MS. Rats were divided into four groups: Healthy Control (HC); Diabetic Control (DC); Healthy?+?Essential Oils (H?+?EO) and Diabetic?+?Essential Oils (D?+?EO). Antidiabetic and antioxidant activities were evaluated after subacute intraperitoneally injection of Lavandula stoechas essential oils (50 mg/kg b.w., i.p.) to rats during 15 days. Results The principal compounds detected are: D-Fenchone (29.28%), ?-pinene (23.18%), Camphor (15.97%), Camphene (7.83%), Eucapur (3.29%), Limonene, (2.71%) Linalool, (2.01%) Endobornyl Acetate (1.03%). The essential oils also contained smaller percentages of Tricyclene, Cymene, Delta-Cadinene, Selina-3,7(11)-diene. Furthermore, we found that Lavandula stoechas essential oils significantly protected against the increase of blood glucose as well as the decrease of antioxidant enzyme activities induced by aloxan treatment. Subacute essential oils treatment induced a decrease of lipoperoxidation as well as an increase of antioxidant enzyme activities. Conclusions These findings suggested that lavandula stoechas essential oils protected against diabetes and oxidative stress induced by alloxan treatment. These effects are in partly due to its potent antioxidant properties. PMID:24373672

2013-01-01

62

Increased severity of acute Trypanosoma brucei brucei infection in rats with alloxan-induced diabetes  

E-print Network

-induced diabetes Ikechukwu Onyebuchi Igbokwea Sani Isaa Umma Kalsum Aliyub Hajja Gana Hamzab Tobias Egbe made diabetic by treatment with alloxan monohydrate (10 % solution, 100 mg/kg body weight). Ten diabetic and ten non-diabetic rats were intraperitoneally infected with the same infective doses

Paris-Sud XI, Université de

63

Biochemical Evaluation of the Hypoglycemic Effects of Extract and Fraction of Cassia fistula Linn. in Alloxan-induced Diabetic Rats  

PubMed Central

Various extracts of flowers of Cassia fistula Linn (Leguminosae) such as petroleum ether (60-80°), chloroform, acetone, ethanol, aqueous, and crude aqueous extracts and two fractions of ethanol extract were tested for antihyperglycemic activity in glucose-overloaded hyperglycemic rats. The effective antihyperglycemic extracts and fraction were tested for their hypoglycemic activity at two dose levels, 200 and 400 mg/kg, respectively. To confirm their utility in higher models, the effective extracts and fraction of C. fistula were subjected to antidiabetic study in an alloxan-induced diabetic model at two dose levels, 200 and 400 mg/kg, respectively. Biochemical parameters like glucose, urea, creatinine, serum cholesterol, serum triglyceride, high-density lipoprotein, low-density lipoprotein, hemoglobin, and glycosylated hemoglobin were also assessed in experimental animals. The petroleum ether and ethanol extracts of C. fistula and the water-soluble fraction of ethanol extract were found to exhibit significant antihyperglycemic activity. The extracts, at the given doses, did not produce hypoglycemia in fasted normal rats, and the fraction exhibited weak hypoglycemic effect after 2 h of the treatment. Treatment of diabetic rats with ethanol extract and water-soluble fraction of this plant restored the elevated biochemical parameters significantly (P<0.05) to the normal level. No activity was found in the petroleum ether extract of the plant. Comparatively, the water-soluble fraction of ethanol extract was found to be more effective than the ethanol extract, and the activity was comparable with that of the standard, glibenclamide (5 mg/kg). PMID:24302797

Jarald, E. E.; Joshi, S. B.; Jain, D. C.; Edwin, S.

2013-01-01

64

The ultrastructure of the capillaries in the gingiva of alloxan-induced diabetic rats.  

PubMed

The diabetic effects of alloxan (type I diabetes mellitus) were investigated in 40 Wistar albino rats (18 controls and 22 diabetics). Alloxan in sterile physiological saline was injected into animals intravenously. After the induction of diabetes with alloxan, the ultrastructure of the capillaries in the gingiva was examined by transmission electron microscopy. The thickness of the basement membranes was observed closely adherent to the endothelial cells of the capillary alloxan-diabetic rats. It was greatly thickened owing to the increase in its amorphous, granular and filamentous material with occasional scattered collagen fibres. In some sections, the capillary lumens of the diabetics were closed by epithelial cells. Loss of cytoplasmic material and hyalinization were seen in some smooth muscle cells. In addition, the mitochondrial cristae of smooth muscle cell and epithelial cells disappeared. There was endothelial integrity throughout the smooth muscle cells. PMID:14624468

Gül, Nursel; Ozsoy, Nesrin

2003-12-01

65

Bone regeneration in cranioplasty and clinical complications in rabbits with alloxan-induced diabetes.  

PubMed

This research evaluated the bone repair process in surgical defects created on the parietal bones of diabetic rabbits using the guided bone regeneration technique to observe the effects of alloxan in the induction of diabetes mellitus. Twenty-four adult rabbits were divided into three study groups: control (C), diabetic (D) and diabetic associated to polytetrafluoroethylene (PTFE) membrane (D-PTFE). For diabetes induction the animals received one dose of monohydrated alloxan (90 mg/kg) by intravenous administration in the auricular or femoral vein. In group D-PTFE the membrane covered both the floor and the surface of the bone defect. In groups D and C, the bone defect was filled up with blood clot. The specimens were fixed in 10% formol and prepared for histomorphometric analysis. The results showed that the 90 mg/kg dose of monohydrate alloxan was sufficient to promote diabetes mellitus when administered in the auricular vein. Bone regeneration was slower in the diabetic group when compared with the control and diabetic-PTFE groups, but there was no significant statistical difference between the two experimental groups (D and D-PTFE). The oral and general clinical complications among the diabetics were weight loss, polyuria, polyphagia and severe chronic gingivitis. PMID:18622490

Vieira, Evanice Menezes Marçal; Ueno, Camila Satie Ferreira; Valva, Vivian Neves; Goulart, Maria das Graças Vilela; Nogueira, Terezinha de Oliveira; Gomes, Mônica Fernandes

2008-01-01

66

Healing of excisional wound in alloxan induced diabetic sheep: A planimetric and histopathologic study  

PubMed Central

Healing of skin wound is a multi-factorial and complex process. Proper treatment of diabetic wounds is still a major clinical challenge. Although diabetes mellitus can occur in ruminants, healing of wounds in diabetic ruminants has not yet been investigated. The aim of this study was to evaluate healing of ovine excisional diabetic wound model. Eight 4-month-old Iranian Makoui wethers were equally divided to diabetic and nondiabetic groups. Alloxan monohydrate (60 mg kg-1, IV) was used for diabetes induction. In each wether, an excisional wound was created on the dorsum of the animal. Photographs were taken in distinct times for planimetric evaluation. Wound samples were taken on day 21 post-wounding for histopathologic evaluations of epidermal thickness, number of fibroblasts and number of new blood vessels. The planimetric study showed slightly delay in wound closure of diabetic animals, however, it was not significantly different from nondiabetic wounds (p ? 0.05). Furthermore, epidermal thickness, number of fibroblasts and number of blood vessels were significantly lower in diabetic group (p < 0.05). We concluded that healing of excisional diabetic wounds in sheep may be compromised, as seen in other species. However, contraction rate of these wounds may not be delayed due to metabolic features of ruminants and these animals might go under surgeries without any serious concern. However, healing quality of these wounds may be lower than normal wounds.

Kazemi-Darabadi, Siamak; Sarrafzadeh-Rezaei, Farshid; Farshid, Amir-Abbas; Baradar-Jalili, Reza

2013-01-01

67

Effects of alloxan-induced diabetes on ischemia-reperfusion injury in rabbit hearts.  

PubMed

Hearts from rabbits with 8-16 weeks of alloxan-diabetes were compared with hearts from normal rabbits to determine whether diabetic myocardium is more sensitive to ischemic injury. In isolated buffer-perfused hearts, left ventricular developed pressure, diastolic pressure, time to peak pressure (TTPP), time to half-maximal relaxation (RT1/2), and positive and negative dP/dt were measured during generation of left ventricular filling curves before and after 90 minutes of low-flow ischemia. Hearts from diabetic rabbits (blood glucose, 384 +/- 28 mg/dl, mean +/- 95% confidence limits) had left ventricular developed and diastolic pressures similar to normal hearts but exhibited significant increases in TTPP and RT1/2 with decreased positive and negative dP/dt. Left ventricular chamber volume relative to heart mass was greater in diabetic than in normal hearts. Recovery of developed pressure after ischemia was similar in normal (41 +/- 16%) and diabetic hearts (47 +/- 13%). In diabetic hearts during recovery from ischemia, TTPP and R1/2 remained increased compared with normal hearts, with positive and negative dP/dt decreased compared with normal hearts, in proportion to the preischemic differences. After ischemia, high-energy phosphates were depleted to the same extent in normal and diabetic rabbits. In coronary ligation experiments, histochemically determined infarct size in diabetic rabbits after 30 minutes occlusion and 24 hours reperfusion was similar to that in normal rabbits when adjusted for a significantly smaller heart weight and a correspondingly smaller anatomic risk region in the diabetic animals. Thus, despite characteristic abnormalities of mechanical function in diabetic hearts, the severity of injury after ischemia with reperfusion was normal for diabetic hearts. PMID:3359580

Vogel, W M; Apstein, C S

1988-05-01

68

Alloxan-induced diabetes reduces sarcolemmal Na+-K+ pump function in rabbit ventricular myocytes.  

PubMed

The effect of diabetes on sarcolemmal Na(+)-K(+) pump function is important for our understanding of heart disease associated with diabetes and design of its treatment. We induced diabetes characterized by hyperglycemia but no other major metabolic disturbances in rabbits. Ventricular myocytes isolated from diabetic rabbits and controls were voltage clamped and internally perfused with the whole cell patch-clamp technique. Electrogenic Na(+)-K(+) pump current (I(p), arising from the 3:2 Na(+)-to-K(+) exchange ratio) was identified as the shift in holding current induced by Na(+)-K(+) pump blockade with 100 micromol/l ouabain in most experiments. There was no effect of diabetes on I(p) recorded when myocytes were perfused with pipette solutions containing 80 mmol/l Na(+) to nearly saturate intracellular Na(+)-K(+) pump sites. However, diabetes was associated with a significant decrease in I(p) measured when pipette solutions contained 10 mmol/l Na(+). The decrease was independent of membrane voltage but dependent on the intracellular concentration of K(+). There was no effect of diabetes on the sensitivity of I(p) to extracellular K(+). Pump inhibition was abolished by restoration of euglycemia or by in vivo angiotensin II receptor blockade with losartan. We conclude that diabetes induces sarcolemmal Na(+)-K(+) pump inhibition that can be reversed with pharmacological intervention. PMID:17020934

Hansen, Peter S; Clarke, Ronald J; Buhagiar, Kerrie A; Hamilton, Elisha; Garcia, Alvaro; White, Caroline; Rasmussen, Helge H

2007-03-01

69

Histopathological abnormalities of prolonged alloxan-induced diabetes mellitus in rabbits.  

PubMed

The objective of this study was to investigate the prolonged complications of untreated diabetes on histomorphology of rabbits. Diabetes mellitus was experimentally induced in one group of New Zealand white male rabbits by intraperitoneal administration of four doses of alloxan @ 80 mg/kg b.w. at weekly intervals following 12 h fasting. Other group of rabbits served as healthy controls that received isotonic saline in a similar manner. The establishment of diabetes mellitus was confirmed by fasting blood glucose levels. For histomorphological study of different organs, 50% of the animals were killed after 7 weeks and the rest after 26 weeks. Routine haematoxylin and eosin stain and Gomori's modified stain were used. The blood glucose level of diabetic rabbits increased significantly throughout the experimental period. The peak values for blood sugar were on the sixth week of the study. Further, histomorphological alterations were recorded in pancreas, kidneys, lungs, heart and brain in diabetic rabbits. However, mild changes were observed in gastrointestinal tract with proliferation of yeasts in the stomach. With the progress of untreated diabetes, the histoanatomical alterations intensify and extend to almost all organs of the body and appear to increase the susceptibility of gastric mucosa to yeast cell proliferation. PMID:19200253

Mir, Sajad Hussain; Darzi, Mohd Maqbool

2009-02-01

70

Nutritional and hypoglycemic effect of fruit pulp of Annona squamosa in normal healthy and alloxan-induced diabetic rabbits.  

PubMed

The nutritive value of the pulp of the edible fruit of Annona squamosa and its effect on various biochemical parameters has been assessed in normal and alloxan-induced diabetic rats. Different doses (2.5, 5.0, 10.0 g/kg b.w.) of fresh fruit pulp of A. squamosa were given to the three groups each of normal healthy and diabetic rabbits orally daily for 1 month. There was a control group of normal as well as diabetic animals which did not receive fruit pulp. Protein efficiency ratio (PER), digestibility coefficient (DC), biological value (BV) and net protein utilization (NPU) were calculated and improvement in the nutritional level was studied by comparing with the control group. Effect of the fruit pulp was also studied on various biochemical parameters, namely fasting blood glucose (FBG), total cholesterol (TCH), HDL-cholesterol, triglyceride (TG), total protein (TPR), alkaline phosphatase (ALKP), serum glutamate oxaloacetate and pyruvate transaminases (SGOT and SGPT), serum creatinine (CRTN) and serum bilirubin (BIL). Protein and glucose in urine were also estimated. Total hemoglobin and glycohemoglobin (HbAc) were estimated in blood before and after 1 month of feeding fruit pulp. Fruit pulp increased the net protein utilization by 29.3 in normal healthy rabbits with 10 g/kg b.w. and 34.1 in induced diabetic (induced by alloxan) animals with 5 g/kg b.w. of the fruit pulp feeding when compared with the control group of rabbits (p < 0.001). Feeding fruit pulp with the same amount increased the total hemoglobin content by 21.0% in normal rabbits and 10.8% in diabetic rabbits. Fruit pulp also reduced the total cholesterol level by 45-46% in normal and 32.4% in diabetic animals with increased HDL-cholesterol. Feeding pulp improved the liver function in normal as well as diabetic rabbit as shown by reduction in the serum SGOT, SGPT, ALKP and bilirubin levels. The optimal improvement in nutritive value of normal animals was found with 5.0-10.0 g/kg b.w. of the fruit pulp feeding, while in diabetic animals it was 2.5-5.0 g/kg b.w. In the diabetic animals pulp feeding between 2.5 and 5.0 g/kg b.w. showed improvement in the glucose tolerance. Further, 5 g/kg b.w. of fruit pulp brought down urine sugar, urine protein and glycohemoglobin in diabetic rabbits. Feeding pulp had increased utilization of dietary protein, body weight as well as the ratio of gain in body weight per gram of protein consumed. It had a protective effect on liver and heart as indicated by reduction in the SGOT, SGPT, ALKP and serum bilirubin levels. PMID:16230844

Gupta, Rajesh Kumar; Kesari, Achyut Narayan; Watal, Geeta; Murthy, P S; Chandra, Ramesh; Tandon, Vibha

2005-01-01

71

Additive effect of lipid lowering drug (simvastatin) in combination with antidiabetic drug (glibenclamide) on alloxan induced diabetic rats with long term dyslipidemia.  

PubMed

High blood glucose level, elevated level of liver enzyme, necrosis and shrinkage of islets of Langerhans has been implicated in the pathogenesis of type 2 diabetes. High blood glucose cause oxidative stress, production of free radical as well as elevated SGPT and SGOT level. Both glibenclamide and simvastatin in fixed dose used as antihyperglycemic antidyslipidemic and antioxidative agents for type 2 diabetes treatment. This study therefore aimed to evaluate the antihyperglycemic, antidyslipidemic and antioxidative effect of fixed dose combination of glibenclamide (0.6 mg/70 kg body weight) and simvastatin (5 mg/70 kg body weight) on long term alloxan induced diabetic rats with cardiovascular disease using various diagnostic kits as a parameter of phamacotherapeutic and pharmacological effect. The study was carried out using 96 Swiss Albino male rats weighing about 200-220 g. Combination therapy induced a significant decrease in blood glucose level in alloxan induced diabetic rats, from 33.75 ± 1.65 to 5.80 ± 0.07 mmol/l 2 h after last dose administration, after 4 weeks treatment. In case of dyslipidemic effect, combination therapy reduced total cholesterol (45 %), triglyceride (36 %) and low density lipoprotein-cholesterol (32 %) levels significantly and increased high density lipoprotein-cholesterol level (57 %) in comparison with their respective diabetic control groups. Results of this study showed that combination therapy effectively decreased SGPT (ALAT) (55 %) and SGOT (ASAT) (51 %) in comparison with diabetic control group. It was also observed that catalase and superoxide dismutase enzyme activity was increased by 58 and 91 % respectively in comparison with diabetic control group after 4 weeks treatment with combination of both drugs. In conclusion, these findings of combination therapy (glibenclamide and simvastatin) on alloxan induced diabetes in rats are significantly better than monotherapy using single drug. The results of the present study suggest that, combination of the fixed dose of glibenclamide and simvastatin might be efficacious in patients with diabetic dyslipidemia and increased oxidative stress. Furthermore, this combination therapy offer dosage convenience to the patients and by virtue of its dual mode of action might be a useful addition to the therapeutic armamentarium for patients with diabetic dyslipidemia and oxidative stress. PMID:25298626

Begum, Mst Marium; Sultana, Zakia; Ershad Ali, Md; Jami, Md Safkath Ibne; Khondkar, Proma; Khan, Md Masuduzzaman; Haque, Md Mominul

2014-10-01

72

Effect of 50% Hydro-Ethanolic Leaf Extracts of Ruellia Tuberosa L. and Dipteracanthus Patulus (Jacq.) on Lipid Profile in Alloxan Induced Diabetic Rats  

PubMed Central

Background: The study was undertaken to investigate the effect of 50% hydro -ethanolic leaf extracts of Ruellia tuberosa L. and Dipteracanthus patulus (Jacq.) on lipid profile in alloxan induced diabetic rats. Method: In lipid profile the parameters studied were serum total cholesterol, phospholipids, triglycerides, HDL-c, LDL-c and VLDL-c level. Extracts were orally administered daily for 30 days at a dosage of 250 and 500 mg/kg bodyweight to alloxan induced diabetic rats. Results: The levels of phospholipids, triglycerides, LDL-c and VLDL-c were significantly (P < 0.05) reduced. The HDL-c level was found to be increased in the treatment groups. Total cholesterol level was found to be significantly (P < 0.05) decreased at 500 mg/kg bodyweight of both the plant extracts treated groups. Conclusion: The results further suggests that the effect of plant extract treated groups was found to be lower in reducing the lipid levels in serum when compared to the drug (Glibenclamide 600 ?g/kg body weight) treated group. PMID:24049591

Ananthakrishnan, Manikandan; Doss, Victor Arokia

2013-01-01

73

Effects of hydro-ethanol extract of Citrullus colocynthis on blood glucose levels and pathology of organs in alloxan-induced diabetic rats  

PubMed Central

Objective To evaluated the differential effects of ethanol extraction of Citrullus colocynthis (C. colocynthis) on the blood glucose concentration and pathology of pancreas, liver, lungs, kidney and gastrointestinal tract in the alloxan induced diabetes in rats. Methods Diabetes mellitus was induced in 20 adult female Albino rats, using intraperitoneal injection of 120 mg/kg alloxan. The diabetic rats were randomly assigned into two equal groups. The first group was treated with the extract of C. colocynthis seed (300 mg/kg) and the rats of the second group, as an untreated diabetic group, received ordinary diet. Ten non diabetic rats remained as a normal control group. Results The results of this study indicate that C. colocynthis was able to reduce blood glucose significantly compared with the control diabetic group (P<0.05). Histopathologically, alloxan resulted in severe necrotic changes in the pancreatic islets, especially in the central area of the islets. Tissue sections of the pancreas in the treated rats demonstrated enhanced regeneration of B cells and increased size of pancreatic islets. Liver of the treated diabetic rats revealed significant improvement of the hepatic tissue compared to those of the untreated diabetic rats. Conclusions The present study indicated a significant anti-hyperglycemic effect of C. colocynthis seed and supported its traditional usage in treatment of diabetes mellitus.

Oryan, Ahmad; Hashemnia, Mohammad; Hamidi, Ahmad-Reza; Mohammadalipour, Adel

2014-01-01

74

Short-term stromal alterations in the rat ventral prostate following alloxan-induced diabetes and the influence of insulin replacement.  

PubMed

The stromal microenvironment is pivotal to prostate physiology and malign transformation. Diabetes leads to testosterone withdrawal and affects the prostate stromal compartment and smooth muscle cells in a similar way to that observed after castration. However the response of these cells and their involvement in extracellular matrix remodeling is not satisfactorily understood. We investigated the changes caused in the short term (one week) by alloxan-induced diabetes in the stromal components of the rat ventral prostate (VP) with an emphasis on morphological alterations of stromal cells, their conversion to a myofibroblast phenotype and the remodeling of extracellular matrix and the influence of insulin therapy. Adult male Wistar rats were assigned into untreated diabetic (n=12), insulin-treated (n=8) diabetic and control (n=10) groups. Diabetes was induced by means of the injection of alloxan (40 mg/kg b.w.), while the control animals received saline solution only. Insulin (5 UI) was administered daily for one week after diabetes diagnosis. Testosterone and estrogen plasma levels were determined. VP was analyzed using transmission electron microscopy. The main stromal cells were identified by means of light microscopy, using immunocytochemistry for specific markers - vimentin for fibroblasts, ?-actin for smooth muscle cells (smc) and vimentin/calponin for myofibroblasts, following the estimation of their relative frequency and absolute volume by means of stereology. After one week diabetes led to a marked decrease in testosterone levels and an atrophy of about 35% in the VP. The relative frequency of smc and collagen fibers increased in the VP of diabetic rats but their absolute weight remained unchanged. Experimental diabetes promptly altered smc morphology which assumed at the ultrastructural level a shrunken appearance with the approximation of cytoplasmic dense bodies and also exhibited a decreased immunoreactivity to calponin. The conversion of stromal cells to a myofibroblast phenotype did not occur in alloxan-induced diabetes, as evaluated by double immunoreaction to calponin and vimentin. Insulin treatment maintained testosterone levels and preserved at least partly the cell morphology and collagen fiber organization of the prostate stroma in short-term diabetes. The apparent collagen increase observed by means of microscopic analysis in the stromal prostate compartment in the short term after diabetes is mainly associated with gland atrophy and does not involve the formation of new collagen fibers, the generation of myofibroblast-like cells or the acquisition of a secretory phenotype by stromal cells. PMID:22014851

Gobbo, Marina Guimarães; Taboga, Sebastião Roberto; Ribeiro, Daniele Lisboa; Góes, Rejane Maira

2012-02-01

75

Hydro-alcoholic extract of the root of Prangos ferulacea (L.) Lindl can improve serum glucose and lipids in alloxan-induced diabetic rats  

PubMed Central

Objectives: Diabetes mellitus manifests itself in a wide variety of complications and the symptoms of this disease are multifactorial. Previous studies proved that this disease is directly related to hyperglycemia and hyperlipidemia. The aim of this study was to investigate the hypoglycemic and hypolipidemic effects of hydroalcoholic extract of Prangos frulacea (L.) Lindl in alloxan-induced diabetic rats. Materials and Methods: Forty female Wistar rats with body weight of 200±20 g were randomly divided into five groups with eight rats per group. Diabetes was induced in rats by alloxan monohydrate at dose of 120 mg/kg body weight (BW) injected intraperitoneally. Hydro-alcoholic extract of the root and leaves with stems of P. frulacea at 100 mg/kg BW were given orally to diabetic rats daily for 4 weeks. Result: Diabetic rats (D) exhibited a significant (p<0.05) increase in the levels of the serum glucose, Total Cholesterol (TC), Triglycerides (TG), and LDL in comparison with the control group whereas their BW and serum HDL levels were decreased. In diabetic rats treated by root extract of P. frulacea, these parameters were reversed to the normal levels compared with diabetic group. Conclusion: According to the results obtained, it was concluded that Root´s hydro-alcoholic extract of P. frulacea can be used in diabetics for the purpose of glucose and lipid profile reduction. PMID:25050248

Kafash Farkhad, Najme; Farokhi, Farah; Tukmacki, Amir; Soltani band, Khosro

2012-01-01

76

Dynamic aspects of amino acid metabolism in alloxan-induced diabetes and insulin-treated rabbits: in vivo studies with 15N and gas chromatography-mass spectrometry.  

PubMed

The present study was designed to determine the effect of alloxan-induced diabetes in rabbits on L-[15N]alanine and [15N]glycine kinetic parameters. This process was measured by single-dose administration of 15N-labeled amino acids to postabsorptive control rabbits and alloxan-induced diabetics and insulin-treated diabetic rabbits. Gas chromatography-mass spectrometry was used to determine the 15N enrichment of plasma glycine and alanine. Glycine and alanine pools and turnover rate constants were estimated from isotope enrichment time decay curves. The data from the present study indicate that plasma glycine and alanine turnover rate constants increased by 25-50% after alloxan administration but pool sizes showed only little changes, resulting in highly significant increases in fluxes and metabolic clearance rates of both alanine and glycine following alloxan administration; single-dose crystalline insulin or protamine zinc insulin treatment failed to restore the turnover rate constants of glycine or alanine toward control values and caused a depletion of 50% in glycine pool size; 7 days prolonged treatment with protamine zinc insulin restored alanine and glycine fluxes and metabolic clearance rates towards control postabsorptive values; and the reduction in flux values following insulin treatment is consistent with the reduction in the plasma glucose levels in rabbits. The data suggest that the regulatory mechanisms for uptake and metabolism of circulating glycogenic amino acids no longer are operative as a consequence of insulin deficiency following alloxan administration. Exogenous insulin restored the activity of the regulatory mechanism toward the postabsorptive control state. PMID:3535838

Nissim, I; Lapidot, A

1986-02-01

77

Mitigating effects of antioxidant properties of Artemisia campestris leaf extract on hyperlipidemia, advanced glycation end products and oxidative stress in alloxan-induced diabetic rats.  

PubMed

Artemisia campestris is used as antivenom and anti-inflammatory Tunisian folk medicine. Recently, increased oxidative stress was shown to play an important role in the etiology and pathogenesis of diabetes mellitus and its complications. This study was designed to examine the effects of A. campestris leaf aqueous extract (Ac) on alloxan-induced diabetic rats by measuring glycemia, lipid profile, lipid peroxidation (MDA), protein carbonyl content (PCO), advanced oxidation protein products (AOPP), activities of both non-enzymatic and enzymatic antioxidants. Results of our study showed an increase in blood glucose levels, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), a decrease in high-density lipoprotein cholesterol (HDL-c) level and disturbed antioxidant enzyme activities (CAT, SOD, GPx) in the pancreatic tissue of diabetic rats. Furthermore, MDA, PCO and AOPP were elevated in the pancreas of the diabetic rats. The administration of Ac to diabetic rats at a dose of 200mgkg(-1)bw resulted in a significant reduction in glycemia, TC, TG, LDL-c, pancreas LPO, PCO and AOPP levels, CAT and GPx activities associated with an elevation of GSH content and SOD activity in comparison with diabetic group. We conclude that A. campestris aqueous extract may be effective for correcting hyperglycemia and preventing diabetic complications. PMID:20457207

Sefi, Mediha; Fetoui, Hamadi; Makni, Mohamed; Zeghal, Najiba

2010-07-01

78

Cytological and biochemical studies during the progression of alloxan-induced diabetes and possible protection of an aqueous leaf extract of Costus afer.  

PubMed

Some plants have proven efficacy in the management of diabetes mellitus, of which Costus afer is one. This study was designed to evaluate the cytological and biochemical properties, and comparative ameliorating effects, of an aqueous extract of Costus afer Ker Gawl. (Costaceae) leaf and glibenclamide (GBM), in liver, kidney, and pancreatic injury induced by alloxan. Thirty male albino rats were divided into six weight-matched groups. Group one served as the negative control (non-induced and non-treated, control), while groups 2-6 were alloxan-induced diabetic groups. Group 2 served as a positive control (induced and non-treated, IC), groups 3-5 were treated with different doses of the extract (375, 750, and 1 125 mg/kg body weight) and glibenclamide, respectively. Body weight, absolute and relative organ weights, food and fluid intake, levels of serum glucose and liver enzymes and kidney parameters were calculated and compared. Hepatocytes, renal tubules, and pancreatic cells of diabetic rats, in diabetic non-treated and treated rats were harvested and examined histopathologically. There was dose dependent amelioration on the injuries induced by alloxan on both hepatocytes, renal tubules, and pancreatic cells after treatment with Costus afer. The glucose level was reduced significantly in the Costus afer treated diabetic rats compared with the non-treated diabetic group. Costus afer leaves seem to be effective against diabetic cell injury induced in rat liver, kidney, and pancreas. PMID:25443367

Ezejiofor, Anthoneth Ndidi; Orish, Chinna Nneka; Orisakwe, Orish Ebere

2014-10-01

79

Effect of aqueous extracts of alligator pear seed (Persea americana mill) on blood glucose and histopathology of pancreas in alloxan-induced diabetic rats.  

PubMed

Effects of aqueous extract of alligator pear seed on normal and alloxan-induced diabetic rats were investigated in 6 groups of rats (5 rats per group). Test groups were made diabetic with intra-peritoneal injection of alloxan and treated with 300 mg and 600 mg/kg body weight of alligator pear seed extract. Two non-diabetic groups were also administered with 300 mg and 600 mg/kg body weight extract. The levels of blood glucose were examined in all 6 experimental groups. In diabetic rats, blood glucose levels were significantly reduced (p<0.05) by 73.26-78.24% on consumption of the extracts, with greater effect exhibited by the 600 mg/kg extract. In normal rats, blood glucose levels were significantly reduced (p<0.05) by 34.68-38.9% on consumption of the seed extract. Histological studies showed a degenerative effect on the pancreatic islet cells of diabetic rats. The result suggested restorative (protective) effect of the extract on pancreatic islet cells. Administration of aqueous extract of alligator pear seed may contribute significantly to the reduction of blood glucose levels and can be useful in the treatment of diabetes. PMID:19553173

Edem, Do; Ekanem, Is; Ebong, Pe

2009-07-01

80

Streptozotocin- and alloxan-induced diabetes modifies total plasma and lipoprotein lipid concentration and composition without altering cholesteryl ester transfer activity.  

PubMed

The objectives of this study were to determine the total plasma and lipoprotein lipid concentration and composition and cholesteryl ester transfer activity in two diabetic animal models (alloxan-induced diabetes in rabbits and streptozotocin-induced diabetes in rats). Furthermore, we wanted to determine if the severity of diabetes influences lipoprotein lipid profiles and cholesteryl ester transfer activity. Rats and rabbits were randomly divided into non-diabetic and diabetic groups. Rats were administered either 55 mg/kg or 100 mg/kg of streptozotocin intravenously through the tail vein, while rabbits were administered 100 mg/kg or 200 mg/kg of alloxan intravenously through the marginal ear vein under light anesthesia. Hyperglycaemia was tested for at 48 hr following the doses. Total and lipoprotein cholesterol and triglyceride concentrations using enzymatic kits and cholesteryl ester transfer activity from low-density lipoproteins to high-density lipoproteins using 3H-cholesteryl ester incorporated into low-density lipoproteins were determined. Elevations in both total and lipoprotein cholesterol and triglyceride concentrations and alterations in lipoprotein lipid composition are observed following the onset of drug-induced diabetes in rats and rabbits compared to non-diabetics. However, these findings were observed only in animals administered the higher streptozotocin and alloxan dose. Furthermore, cholesteryl ester transfer from low-density lipoproteins to high-density lipoproteins is not significantly different in drug-induced diabetic compared to non-diabetic rats and rabbits, regardless of which streptozotocin and alloxan dose was used. These findings suggest that difference in lipoprotein lipid concentration and composition as a result of drug-induced diabetes is independent of cholesteryl ester transfer activity in both rats and rabbits. Furthermore, diabetic severity may influence lipoprotein metabolism in these animal models. PMID:9820878

Wasan, K M; Ng, S P; Wong, W; Rodrigues, B B

1998-10-01

81

Therapy with methanolic extract of Pterocarpus marsupium Roxb and Ocimum sanctum Linn reverses dyslipidemia and oxidative stress in alloxan induced type I diabetic rat model.  

PubMed

Methanolic extracts of Pterocarpus marsupium Roxb (P. marsupium) and Ocimum sanctum Linn (O. sanctum) were prepared separately and then administered to both non-diabetic and alloxan induced diabetic adult female Wistar rats as a mixture of both at a dosage of 500mg/kg body weight, and its effect was checked on serum and tissue lipids together with corticosterone, estrogen and progesterone profile. Further, tissue load of metabolites (cholesterol), enzymatic and non-enzymatic antioxidant status together with lipid peroxidation levels and serum markers of hepatic and renal damage were also assessed. Results of the present study strongly support the possibility of this herbal combination in humans to meet the objective of achieving a holistic amelioration and cure of diabetes as, the herbal extract mixture of P. marsupium and O. sanctum has succeeded in not only rectifying dyslipidemia but also in restoring the endogenous antioxidant levels to the pre diabetic status. Herbal preparations are ideal candidates of choice and in this context, the present combination of P. marsupium and O. sanctum provides compelling evidence for a holistic efficacy in amelioration of associated diabetic manifestations/dysregulations. PMID:21106356

Singh, Prem Kumar; Baxi, Darshee; Banerjee, Sudip; Ramachandran, A V

2012-07-01

82

Moringa oleifera leaf extract ameliorates alloxan-induced diabetes in rats by regeneration of ? cells and reduction of pyruvate carboxylase expression.  

PubMed

Moringa oleifera Lam. contains many active ingredients with nutritional and medicinal values. It is commonly used in folk medicine as an antidiabetic agent. The present study was designed to investigate how an aqueous extract from the leaves of M. oleifera reveals hypoglycemia in diabetic rats. M. oleifera leaf extract counteracted the alloxan-induced diabetic effects in rats as it normalized the elevated serum levels of glucose, triglycerides, cholesterol, and malondialdehyde, and normalized mRNA expression of the gluconeogenic enzyme pyruvate carboxylase in hepatic tissues. It also increased live body weight gain and normalized the reduced mRNA expression of fatty acid synthase in the liver of diabetic rats. Moreover, it restored the normal histological structure of the liver and pancreas damaged by alloxan in diabetic rats. This study revealed that the aqueous extract of M. oleifera leaves possesses potent hypoglycemic effects through the normalization of elevated hepatic pyruvate carboxylase enzyme and regeneration of damaged hepatocytes and pancreatic ? cells via its antioxidant properties. PMID:25289966

Abd El Latif, Amira; El Bialy, Badr El Said; Mahboub, Hamada Dahi; Abd Eldaim, Mabrouk Attia

2014-10-01

83

Supplementation with apple enriched with L-arginine may improve metabolic control and survival rate in alloxan-induced diabetic rats.  

PubMed

Supplementation with L-arginine or fresh food with high content of this amino acid is associated with favorable effects in the metabolic control of diabetes. We aimed to determine whether supplementation with apples enriched with L-arginine offer additional benefits compared to L-arginine by itself in a preclinical study of diabetes. This study combines food-engineer technologies with in vivo and in vitro analysis. In vitro experiments show that cells derived from non-diabetic animals and exposed to high glucose (25 mM, 12 H) and cells isolated from alloxan-induced diabetic animals exhibited a reduction (?50%) in the L-arginine uptake. This effect was reverted by L-arginine pretreatment (12 H) in both the normal and diabetes-derived cells. In preclinical studies, normoglycemic (n = 25) and diabetic groups (n = 50) were divided into subgroups that received either L-arginine (375 mg/kg per 10 days) or apple enriched with L-arginine or vehicle (control). In a preliminary analysis, supplementation with L-arginine by itself (50%) or apple enriched with L-arginine (100%) improve survival rate in the diabetic group compared to control (0%) at the end of the follow up (17 days). This phenomenon was associated with a partial but sustained high plasma level of L-arginine, as well as plasma concentration of nitrites and insulin in the L-arginine or apple + L-arginine groups after supplementation. Apple + L-arginine supplementation in diabetic animals induced the highest and longest effects in the level of these three markers among the studied groups. Therefore, apple enriched by L-arginine offers more benefits than L-arginine by itself in this preclinical study. PMID:23553786

Escudero, Andrea; Petzold, Guillermo; Moreno, Jorge; Gonzalez, Marcelo; Junod, Julio; Aguayo, Claudio; Acurio, Jesenia; Escudero, Carlos

2013-01-01

84

Ameliorative effect of Cassia auriculata L. leaf extract on glycemic control and atherogenic lipid status in alloxan-induced diabetic rabbits.  

PubMed

Oral administration of aqueous leaf extract of Cassia auriculata L. (100, 200, 400 and 600 mg/kg body wt daily for 21 days) to alloxan-induced mild diabetic (MD) and severe diabetic (SD) rabbits produced dose dependent fall in fasting blood glucose up to 400 mg/kg dose from day 3 to day 21. Further, a significant elevation in the levels of insulin and reduction in glycosylated haemoglobin (HbA1c) was observed in both MD and SD rabbits when treated with 400 mg/kg dose of the extract. The significant decrease in serum levels of triglycerides (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) with a concomitant increase in high-density lipoprotein-cholesterol (HDL-C) was exhibited by MD as well as SD rabbits following treatment with the extract. Atherogenic indices (TG/HDL-C, TC/HDL-C and LDL-C/HDL-C) were also significantly reduced in both diabetic models of rabbits fed with the extract. Effect of the extract at 400 mg/kg dose was comparable to that of glibenclamide (600 microg/kg), a reference antidiabetic drug. Thus, the present study demonstrated that aqueous leaf extract of C. auriculata can be a possible candidate for antidiabetic drug. PMID:20329701

Gupta, Shipra; Sharma, Suman B; Prabhu, Krishna M

2009-12-01

85

The Effect of Extract/Fractions of Caralluma tuberculata on Blood Glucose Levels and Body Weight in Alloxan-Induced Diabetic Rabbits.  

PubMed

Caralluma tuberculata is a cooked food item in Pakistan especially for diabetics. The current study was designed to explore the antidiabetic potential of extract/fractions of Caralluma tuberculata in alloxan-induced diabetic rabbits and its effect on body weight. The crude extract of the plant provoked 24% and 44% antidiabetic action at 25 and 50 mg/kg OP, respectively, after the 24th day of treatment, which was strongly supported by a positive effect on the body weight of animals. On fractionation, pretreatment of the ethyl acetate fraction demonstrated most dominant (25.17% and 34.83%) antidiabetic activity followed by n-hexane (19.33% and 32.76%) and aqueous fractions (16.44% and 22.36%) at 25 and 50 mg/kg OP, respectively, after the 24th day of treatment. The corresponding effect on blood glucose was also observed on body weight of diabetic rabbits. In sum, extract/fractions of the plant showed marked antidiabetic action and thus a provided scientific foundation to the use of the plant as an antidiabetic. PMID:24742609

Sultan, Khushbakht; Zakir, Muhammad; Khan, Haroon; Khan, Ihsaan Ullah; Rehman, Ali; Akber, Noor Ul; Muhammad, Naveed; Khan, Murad Ali

2014-04-17

86

Anti-diabetic activities of the methanol leaf extracts of Hymenocardia acida (tul.) in alloxan-induced diabetic rats.  

PubMed

The effect of methanolic extract of Hymenocardia acida leaves on diabetes and associated lipidemia were investigated on experimentally-induced diabetic rats. The extract did not demonstrate any acutely toxic effect in rats within the dose range (250 mg/kg - 2000 mg/kg) employed in the study; hence it was well tolerated by the rats. In all experiments, the anti-diabetic effects were dose-dependent and comparable to that of glibenclamide (2 mg/kg) standard. At a dose of 500 mg/kg, lipid profile markers such as the serum total cholesterol (TC) levels, LDL-C, triglycerides and HDL-C were significantly lower (p <0.05) than those of both the treated and untreated controls. PMID:23983336

Ezeigbo, Ihechiluru I; Asuzu, Isaac U

2012-01-01

87

Autologous circulating angiogenic cells treated with osteopontin and delivered via a collagen scaffold enhance wound healing in the alloxan-induced diabetic rabbit ear ulcer model  

PubMed Central

Introduction Diabetic foot ulceration is the leading cause of amputation in people with diabetes mellitus. Peripheral vascular disease is present in the majority of patients with diabetic foot ulcers. Despite standard treatments there exists a high amputation rate. Circulating angiogenic cells previously known as early endothelial progenitor cells are derived from peripheral blood and support angiogenesis and vasculogenesis, providing a potential topical treatment for non-healing diabetic foot ulcers. Methods A scaffold fabricated from Type 1 collagen facilitates topical cell delivery to a diabetic wound. Osteopontin is a matricellular protein involved in wound healing and increases the angiogenic potential of circulating angiogenic cells. A collagen scaffold seeded with circulating angiogenic cells was developed. Subsequently the effect of autologous circulating angiogenic cells that were seeded in a collagen scaffold and topically delivered to a hyperglycemic cutaneous wound was assessed. The alloxan-induced diabetic rabbit ear ulcer model was used to determine healing in response to the following treatments: collagen seeded with autologous circulating angiogenic cells exposed to osteopontin, collagen seeded with autologous circulating angiogenic cells, collagen alone and untreated wound. Stereology was used to assess angiogenesis in wounds. Results The cells exposed to osteopontin and seeded on collagen increased percentage wound closure as compared to other groups. Increased angiogenesis was observed with the treatment of collagen and collagen seeded with circulating angiogenic cells. Conclusions These results demonstrate that topical treatment of full thickness cutaneous ulcers with autologous circulating angiogenic cells increases wound healing. Cells exposed to the matricellular protein osteopontin result in superior wound healing. The wound healing benefit is associated with a more efficient vascular network. This topical therapy provides a potential novel therapy for the treatment of non-healing diabetic foot ulcers in humans. PMID:24444259

2013-01-01

88

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

PubMed Central

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-?-Lrhamnopyranosyl]-?-D-galactopyranoside 3 and chrysoeriol 7-O-?-D-galactopyranosyl(1?2)-?-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

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

2013-01-01

89

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

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

Okpashi, Victor Eshu; Bayim, Bayim Peter-Robins; Obi-Abang, Margaret

2014-01-01

90

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

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

Okpashi, Victor Eshu; Bayim, Bayim Peter-Robins; Obi-Abang, Margaret

2014-01-01

91

Anion Gap Toxicity in Alloxan Induced Type 2 Diabetic Rats Treated with Antidiabetic Noncytotoxic Bioactive Compounds of Ethanolic Extract of Moringa oleifera.  

PubMed

Moringa oleifera (MO) is used for a number of therapeutic purposes. This raises the question of safety and possible toxicity. The objective of the study was to ascertain the safety and possible metabolic toxicity in comparison with metformin, a known drug associated with acidosis. Animals confirmed with diabetes were grouped into 2 groups. The control group only received oral dose of PBS while the test group was treated with ethanolic extract of MO orally twice daily for 5-6 days. Data showed that the extract significantly lowered glucose level to normal values and did not cause any significant cytotoxicity compared to the control group (P = 0.0698); there was no gain in weight between the MO treated and the control groups (P > 0.8115). However, data showed that treatment with an ethanolic extract of MO caused a decrease in bicarbonate (P < 0.0001), and more than twofold increase in anion gap (P < 0.0001); metformin treatment also decreased bicarbonate (P < 0.0001) and resulted in a threefold increase in anion gap (P < 0.0001). Conclusively, these data show that while MO appears to have antidiabetic and noncytotoxic properties, it is associated with statistically significant anion gap acidosis in alloxan induced type 2 diabetic rats. PMID:25548560

Omabe, Maxwell; Nwudele, Chibueze; Omabe, Kenneth Nwobini; Okorocha, Albert Egwu

2014-01-01

92

Anion Gap Toxicity in Alloxan Induced Type 2 Diabetic Rats Treated with Antidiabetic Noncytotoxic Bioactive Compounds of Ethanolic Extract of Moringa oleifera  

PubMed Central

Moringa oleifera (MO) is used for a number of therapeutic purposes. This raises the question of safety and possible toxicity. The objective of the study was to ascertain the safety and possible metabolic toxicity in comparison with metformin, a known drug associated with acidosis. Animals confirmed with diabetes were grouped into 2 groups. The control group only received oral dose of PBS while the test group was treated with ethanolic extract of MO orally twice daily for 5-6 days. Data showed that the extract significantly lowered glucose level to normal values and did not cause any significant cytotoxicity compared to the control group (P = 0.0698); there was no gain in weight between the MO treated and the control groups (P > 0.8115). However, data showed that treatment with an ethanolic extract of MO caused a decrease in bicarbonate (P < 0.0001), and more than twofold increase in anion gap (P < 0.0001); metformin treatment also decreased bicarbonate (P < 0.0001) and resulted in a threefold increase in anion gap (P < 0.0001). Conclusively, these data show that while MO appears to have antidiabetic and noncytotoxic properties, it is associated with statistically significant anion gap acidosis in alloxan induced type 2 diabetic rats.

2014-01-01

93

Inhibition of key enzymes related to diabetes and hypertension by Eugenol in vitro and in alloxan-induced diabetic rats.  

PubMed

The present study investigated the effect of treating diabetic rats with eugenol (EG). In vitro enzyme activity was measured in the presence of eugenol, and it was found to inhibit pancreatic ?-amylase (IC(50) = 62.53 µg/mL) and lipase (IC(50) = 72.34 µg/mL) as well as angiotensin converting enzyme (ACE) activity (IC50 = 130.67 µg/mL). In vivo, EG reduced the activity of amylase in serum, pancreas and intestine also the peak level of glucose by 60% compared to diabetic rats. Furthermore, eugenol similar to acarbose reduced serum glycosylated hemoglobin (HbA1c), lipase and ACE levels. In addition, treatments with EG showed notable decrease in serum total-cholesterol, triglycerides and low density lipoprotein-cholesterol levels with an increase of high density lipoprotein-cholesterol. Overall, EG significantly reverted back to near normal the values of the biochemical biomarkers such as transaminases (AST&ALT), alkaline phosphatase (ALP), creatine phosphokinase (CPK) and gamma-glutamyl transpeptidase (GGT) activities, total-bilirubin, creatinine, urea and uric acid rates. PMID:23886079

Mnafgui, Kais; Kaanich, Fatima; Derbali, Amal; Hamden, Khaled; Derbali, Fatma; Slama, Sadok; Allouche, Noureddine; Elfeki, Abdelfattah

2013-12-01

94

Effect of zinc on the lipid peroxidation and the antioxidant defense systems of the alloxan-induced diabetic rabbits.  

PubMed

The effects of oral zinc supplementation on lipid peroxidation and the antioxidant defense system of alloxan (80-90 mg/kg)-induced diabetic rabbits were examined. Forty-five New Zealand male rabbits, 1 year old, weighing approximately 2.5 kg, were allocated randomly and equally as control, diabetic, and zinc-supplemented diabetic groups. After diabetes was induced, zinc-supplemented diabetic rabbits had 150 mg/L of zinc as zinc sulfate (ZnSO(4)) in their drinking tap water for 3 months. The feed and water consumption was higher in diabetic groups than (P<0.01) healthy rabbits. The body weight was lower in diabetic rabbits compared to control. The blood glucose levels were higher in diabetic groups than controls. The elevated plasma malondialdehyde (MDA) levels were determined in the diabetic group (P<0.01). The glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and ceruloplasmin levels in the diabetic group were decreased by the effect of diabetes but there was no difference between zinc-supplemented diabetic and control rabbits. Serum zinc concentrations were lower in diabetic rabbits but iron (Fe) and copper (Cu) levels in sera were not different among the groups. As a result, it was concluded that daily zinc supplementation could reduce the harmful effects of oxidative stress in diabetics. PMID:17448894

Duzguner, Vesile; Kaya, Sule

2007-05-15

95

Effect of Croatian propolis on diabetic nephropathy and liver toxicity in mice  

PubMed Central

Background In the present study, we examined the antioxidant effect of water soluble derivative of propolis (WSDP) and ethanolic (EEP) extract of propolis on renal and liver function in alloxan-induced diabetic mice. In addition, we examined whether different extract of propolis could prevent diabetic nephropathy and liver toxicity by inhibiting lipid peroxidation in vivo. Methods Diabetes was induced in Swiss albino mice with a single intravenous injection of alloxan (75?mg?kg-1). Two days after alloxan injection, propolis preparations (50?mg?kg-1 per day) were given intraperitoneally for 7?days in diabetic mice. Survival analysis and body weights as well as hematological and biochemical parameters were measured. The renal and liver oxidative stress marker malonaldehyde levels and histopathological changes were monitored in the liver and kidney of treated and control mice. Results Administration of propolis to diabetic mice resulted in a significant increase of body weight, haematological and immunological parameters of blood as well as 100% survival of diabetic mice. Alloxan-injected mice showed a marked increase in oxidative stress in liver and kidney homogenate, as determined by lipid peroxidation. Histopathological observation of the liver sections of alloxan-induced diabetic mice showed several lesions including cellular vacuolization, cytoplasmic eosinophilia and lymphocyte infiltrations, but with individual variability.Treatment of diabetic mice with propolis extracts results in decreased number of vacuolized cells and degree of vacuolization; propolis treatment improve the impairment of fatty acid metabolism in diabetes. Renal histology showed corpuscular, tubular and interstitial changes in alloxan-induced diabetic mice. Test components did not improve renal histopathology in diabetic mice. Conclusions Propolis preparations are able to attenuate diabetic hepatorenal damage, probably through its anti-oxidative action and its detoxification proccess as well as the potential to minimize the deleterious effects of free radicals on tissue. The protective role of propolis against the ROS induced damages in diabetic mice gives a hope that they may have similar protective action in humans. PMID:22866906

2012-01-01

96

Antihyperglycaemic effect and acute toxicity of Securigera Securidaca L. seed extracts in mice.  

PubMed

The antihyperglycaemic activity of a Securigera securidaca aqueous infusion and an ethanol maceration extract of seeds was studied in normoglycaemic, glucose-induced hyperglycaemic and alloxan-induced diabetic mice. The acute toxicity of the ethanol extract was more than that of the aqueous one. The phytochemical analysis showed that the seed extracts were rich in flavonoids. The intraperitoneal and oral administration of the aqueous and ethanol extracts significantly reduced blood glucose in alloxan-induced diabetic mice. In normoglycaemic and glucose-induced hyperglycaemic mice, the blood glucose levels were not significantly different from the control. Glibenclamide was not able to lower blood glucose in alloxan-induced diabetic mice, while it significantly lowered the blood sugar in normoglycaemic mice. The results indicate that S. securidaca seed extracts significantly reduce blood glucose in alloxan-induced diabetic mice by a mechanism different from that of sulfonylurea agents. PMID:12458478

Hosseinzadeh, H; Ramezani, M; Danaei, A R

2002-12-01

97

Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated parotid artery of the alloxan-induced diabetic rabbit.  

PubMed

The aim of this study was to assess the effect of type 1 diabetes mellitus (induced by a single intravenous injection of 100 mg kg(-1) of alloxan) on acetylcholine (ACh)-induced relaxation in isolated rabbit parotid gland feeding artery. Isometric force measurements and quantification of inducible nitric oxide synthase (iNOS) mRNA by real-time RT-PCR were made in parotid artery rings from diabetic and control rabbits. Acetylcholine induced concentration- and endothelium-dependent vasorelaxation that was significantly decreased in parotid artery rings from diabetic rabbits. Schild analysis of the ACh vasorelaxant effect, in the presence of selective muscarinic receptor antagonists, revealed involvement of the M(3) receptor subtype in parotid artery rings from both control and diabetic rabbits, with no change in antagonist affinity constants. The inhibitory effects of indomethacin, a non-selective inhibitor of cyclooxygenase, and of high potassium, an inhibitor of hyperpolarization, on ACh vasorelaxation were increased. The effect of N(G) -nitro-l-arginine, a non-selective inhibitor of NOS, was decreased in diabetes. S-methylisothiourea, a selective inhibitor of iNOS, significantly reduced ACh vasorelaxation only in parotid artery rings from diabetic rabbits. Also, up-regulation of iNOS mRNA expression was detected in parotid artery rings from diabetic rabbits. These results suggest that in parotid artery rings from diabetic rabbits, impaired endothelium-dependent vasorelaxation to ACh appears to be caused by the loss of a nitric oxide-mediated component and increased iNOS expression, and is unlikely to be caused by a change at the M(3) receptor level. PMID:21896051

Roganovi?, Jelena; Radenkovi?, Miroslav; Tani?, Nikola; Tani?, Nasta; Petrovi?, Nina; Stoji?, Dragica

2011-10-01

98

Hypoglycaemic effects of Methanolic extract of Canscora decussata (Schult) whole-plant in normal and alloxan-induced diabetic rabbits.  

PubMed

In present study hypoglycaemic effects of the crude powdered C. decussata and its methanolic extract (ME) in alloxan diabetic rabbits were evaluated. The hypoglycaemic effect was measured by blood glucose, insulin level, HbA1c and his to pathology of pancreas. Glucose lowering effect of the ME was studied in diabetic rabbits. The effects of extract on blood glucose, body weight, food in take, fluid intake, OGTT were also evaluated. The results showed that 0.5,1 and 2g/kg of the powder significantly decreased blood glucose levels in normal rabbits and diabetic rabbits at the intervals checked. Oral intake of pioglitazone also reduced the levels in these rabbits. Synergistic hypoglycaemic effect of 600mg/kg of ME with different doses of insulin (2 & 3unit/kg, s/c) further reduced blood glucose levels of treated alloxan-diabetic rabbits. The oral glucose tolerance test revealed lowered area under curve values in ME treated rabbits. Treatment with ME (400 and 600 mg/kg) for 30 days showed highly significant decrease in blood glucose level by augmenting insulin secretion, HbA1cand significant increase in body weight, serum insulin levels in treated diabetic rabbits. Histopathology study showed regeneration of ?-cells. These studies have, therefore, supported the traditional use of this herb in diabetic patients. PMID:25553693

Irshad, Nadeem; Akhtar, Muhammad Shoaib; Bashir, Sajid; Hussain, Azhar; Shafiq, Muhammad; Iqbal, Javeid; Malik, Abdul

2015-01-01

99

Antidiabetic and antihyperlipidemic effects of ethanolic extract of leaves of Punica granatum in alloxan-induced non–insulin-dependent diabetes mellitus albino rats  

PubMed Central

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

Das, Swarnamoni; Barman, Sarajita

2012-01-01

100

Comprehensive Evaluation of Anti-hyperglycemic Activity of Fractionated Momordica charantia Seed Extract in Alloxan-Induced Diabetic Rats.  

PubMed

The present study evaluates anti-hyperglycemic activity of fractionated Momordica charantia (bitter gourd) seed extracts. Fasting blood glucose levels were evaluated before and after administration of different fractions of the seed extract. Among the three fractions tested, fraction Mc-3 (15?mg/kg b.wt.) showed the maximum anti-hyperglycemic activity and reduced blood glucose levels in experimental diabetic rats significantly. The activities of the key regulatory enzymes of glucose metabolism (hexokinase, pyruvate kinase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase) were determined in Mc-3-treated diabetic animals. Once-daily administration of the fraction Mc-3 for prolonged period of 18 days to the experimental diabetic animals did not result in any nephrotoxicity or hepatotoxicity as evident from insignificant changes in biochemical parameters indicative of liver and kidney functions. Further fractionation of the fraction Mc-3 by size exclusion chromatography resulted in a fraction, designated Mc-3.2, possessing anti-hyperglycemic activity. The fraction Mc-3.2 showed the presence of a predominant protein band of ~11?kDa on SDS-PAGE. Loss in anti-hyperglycemic activity of the Mc-3.2 upon protease treatment indicates the proteinaceous nature of the anti-hyperglycemic principles. Overall, the results suggest that Momordica charantia seeds contain an effective anti-hyperglycemic protein(s) which may find application in treatment of diabetes without evident toxic effects. PMID:23320026

Choudhary, Shailesh Kumar; Chhabra, Gagan; Sharma, Dipali; Vashishta, Aruna; Ohri, Sujata; Dixit, Aparna

2012-01-01

101

Comprehensive Evaluation of Anti-hyperglycemic Activity of Fractionated Momordica charantia Seed Extract in Alloxan-Induced Diabetic Rats  

PubMed Central

The present study evaluates anti-hyperglycemic activity of fractionated Momordica charantia (bitter gourd) seed extracts. Fasting blood glucose levels were evaluated before and after administration of different fractions of the seed extract. Among the three fractions tested, fraction Mc-3 (15?mg/kg b.wt.) showed the maximum anti-hyperglycemic activity and reduced blood glucose levels in experimental diabetic rats significantly. The activities of the key regulatory enzymes of glucose metabolism (hexokinase, pyruvate kinase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase) were determined in Mc-3-treated diabetic animals. Once-daily administration of the fraction Mc-3 for prolonged period of 18 days to the experimental diabetic animals did not result in any nephrotoxicity or hepatotoxicity as evident from insignificant changes in biochemical parameters indicative of liver and kidney functions. Further fractionation of the fraction Mc-3 by size exclusion chromatography resulted in a fraction, designated Mc-3.2, possessing anti-hyperglycemic activity. The fraction Mc-3.2 showed the presence of a predominant protein band of ~11?kDa on SDS-PAGE. Loss in anti-hyperglycemic activity of the Mc-3.2 upon protease treatment indicates the proteinaceous nature of the anti-hyperglycemic principles. Overall, the results suggest that Momordica charantia seeds contain an effective anti-hyperglycemic protein(s) which may find application in treatment of diabetes without evident toxic effects. PMID:23320026

Choudhary, Shailesh Kumar; Chhabra, Gagan; Sharma, Dipali; Vashishta, Aruna; Ohri, Sujata; Dixit, Aparna

2012-01-01

102

Hypoglycemic and antioxidant effects of leaf essential oil of Pelargonium graveolens L’Hér. in alloxan induced diabetic rats  

PubMed Central

Background Rose-scented geranium (Pelargonium graveolens L’Hér.), which is used in traditional Tunisian folk medicine for the treatment of hyperglycaemia, is widely known as one of the medicinal herbs with the highest antioxidant activity. The present paper is conducted to test the hypoglycemic and antioxidative activities of the leaf essential oil of P. graveolens. Methods The essential oil P. graveolens was administered daily and orally to the rats at two doses of 75?mg/kg and 150?mg/kg body weight (b.w.) for 30?days. The chemical composition of P. graveolens essential oil, body weight, serum glucose, hepatic glycogen, thiobarbituric acid-reactive substances (TBARS), the components of hepatic, and renal and serum antioxidant systems were evaluated. The hypoglycemic effect of rose-scented geranium was compared to that of the known anti-diabetic drug glibenclamide (600??g/kg b.w.). Results After the administration of two doses of essential oil of Pelargonium graveolens L’Hér. together with glibenclamide which is known by its antidiabetic activities and used as reference (600??g/kg b.w.), for four weeks, the serum glucose significantly decreased and antioxidant perturbations were restored. The hypoglycemic effect of P. graveolens at the dose of 150?mg/kg b.w. was significantly (pdiabetic rats that these beneficial effects of geranium oils were confirmed. Conclusions It suggests that administration of essential oil of P. graveolens may be helpful in the prevention of diabetic complications associated with oxidative stress. Our results, therefore, suggest that the rose-scented geranium could be used as a safe alternative antihyperglycemic drug for diabetic patients. PMID:22734822

2012-01-01

103

Effect of biologically synthesized gold nanoparticles on alloxan-induced diabetic rats-an in vivo approach.  

PubMed

Development of novel antidiabetic agents using various organic compounds and biomolecules has been in practice for a long time. Recently, nanomaterials are also being used in antidiabetic studies for their unique properties such as small size, biocompatibility and ability to penetrate cell membrane for carrying drugs. Herein, in vivo antidiabetic activity of gold nanoparticles (AuNPs) synthesized using the antidiabetic potent plant Gymnema sylvestre R. Br on wistar albino rats has been evaluated. The formation of AuNPs and their morphology were confirmed using spectroscopic and microscopic analyses, respectively. The treatment of AuNPs has shown significant reduction in blood glucose level on diabetic rats. AuNPs were also tested for its anti-inflammatory effect by estimating the serum levels of tumor necrosis factor-alpha (TNF-?), interleukin-6 (IL-6) and high-sensitive C-reactive protein (CRP). PMID:25092583

Karthick, V; Kumar, V Ganesh; Dhas, T Stalin; Singaravelu, G; Sadiq, A Mohamed; Govindaraju, K

2014-10-01

104

Antidiabetic, antilipidemic, and antioxidant activities of Gouania longipetala methanol leaf extract in alloxan-induced diabetic rats.  

PubMed

Abstract Context: Gouania longipetala Hemsl. (Rhamnaceae) is used in folkloric medicine for treating diabetes mellitus and its associated symptoms. Objective: This study evaluated the antidiabetic antilipidemic and antioxidant activities of the plant methanol leaf extract. Materials and methods: Diabetes was induced in rats by intraperitoneal injection of alloxan monohydrate (160?mg/kg). Three test doses (50, 100, and 150?mg/kg) of G. longipetala extract (GLE) were administered orally and the effects were compared with glibenclamide (2?mg/kg). The effect of GLE on hyperglycemia and sub-acute study for 21?d were carried out using its effect on fasting blood sugar (FBS) level. Serum biochemistry and antioxidant activity were evaluated. Histopathological evaluation of the pancreas was also done. Results: The LD50 of G. longipetala was found to be >4000?mg/kg. The extract significantly (p?

Ezeja, Maxwell Ikechukwu; Anaga, Aruh Ottah; Asuzu, Isaac U

2014-10-21

105

Antihyperglycemic effect of Trigonella foenum-graecum (fenugreek) seed extract in alloxan-induced diabetic rats and its use in diabetes mellitus: a brief qualitative phytochemical and acute toxicity test on the extract.  

PubMed

The effects of ethanol extract of Trigonella foenum-graecum (Fenugreek) seeds on the blood glucose levels in alloxan-induced diabetic rats at different doses (2 g/kg, 1 g/kg, 0.5 g/kg and 0.1 g/kg) were studied. The hypoglycemic effect of extract was compared with that of the standard antidiabetic drug (glimepiride, 4 mg/kg) single dose. The extract showed significant activity against the diabetic state induced by alloxan but the intensity of hypoglycemic effect varied from dose to dose. The most effective dose recognized was 1 g/kg but that is still lower than the standard antidiabetic drug. No acute toxicity was observed for ethanol extract of T. foenum-graecum seed when it was administered orally at high dose level (3 g/kg body weight), which is higher than effective antihyperglycemic dose, and closely observed for 24 hrs for any mortality and next 10 days for any delayed toxic effects on gross behavioral activities. Phytochemical group tests were also accomplished and presence of alkaloids, steroids and carbohydrates were recognized in the extract. PMID:20448850

Mowla, Asmena; Alauddin, M; Rahman, Md Atiar; Ahmed, Kabir

2009-01-01

106

Efficacy of Composite Extract from Leaves and Fruits of Medicinal Plants Used in Traditional Diabetic Therapy against Oxidative Stress in Alloxan-Induced Diabetic Rats  

PubMed Central

Oxidative stress plays a vital role in diabetic complications. To suppress the oxidative stress mediated damage in diabetic pathophysiology, a special focus has been given on composite extract (CE) and making small dose of naturally occurring antidiabetic plants leaf and fruits. The aim of the present study was to evaluate the beneficial role of CE against alloxan- (ALX-) induced diabetes of Wistar strain rats. A dose-dependent study for CE (25, 50, and 100?mg/kg body weight) was carried out to find the effective dose of the composite compound in ALX-induced diabetic rats. ALX exposure elevated the blood glucose, plasma advanced oxidation product (AOPP), sialic acid demonstrating disturbed antioxidant status.CE at a dose of 100?mg/kg body weight restored/minimised these alterations towards normal values. In conclusion, small dose of CE possesses the capability of ameliorating the oxidative stress in ALX-induced diabetes and thus could be a promising approach in lessening diabetic complications. PMID:24729889

Kumar, Dileep; Abidi, A. B.

2014-01-01

107

Effect of methanolic extract of Tetrapleura tetraptera (Schum and Thonn) Taub leaves on hyperglycemia and indices of diabetic complications in alloxan-induced diabetic rats  

PubMed Central

Objective To investigate the ameliorative role of Tetrapleura tetraptera (Schum and Thonn) Taub (T. tetraptera) leaf in hyperglycemia with associated conditions like oxidative stress, kidney damage and disorders in lipid metabolism. Methods Five groups of five rats each intraperitoneally received the following treatment schedules for 7 d: untreated normal control, untreated alloxan-diabetic control, diabetic treated with glibenclamide, normal rats treated with extract (50 mg/kg) and diabetic rats treated with the extract. Evaluations were made for fasting blood sugar, body weight changes, malondialdehyde, aspartate aminotransferase, alanine aminotransferase, bilirubin, superoxide dismutase, catalase, lipid profile, packed cell volume, hemoglobin, urea and creatinine in all the rats. Results Whereas the untreated diabetic rats showed a significant decrease (P<0.05) in packed cell volume, superoxide dismutase, catalase and high-density lipoprotein-cholesterol with a concomitant increase in the levels of malondialdehyde, fasting blood sugar, aspartate aminotransferase, alanine aminotransferase, bilirubin, urea and creatinine, administration of methanolic extract of T. tetraptera leaf or glibenclamide alleviated these altered parameters in the treated rats. Conclusions Methanolic extract of T. tetraptera leaves possesses a potent capacity for treatment of diabetes and the accompanying complications, including oxidative stress and hyperlipidemia. PMID:25182550

Atawodi, Sunday Ene-Ojo; Yakubu, Ojochenemi Ejeh; Liman, Mubarak Labaran; Iliemene, Dorothy Uju

2014-01-01

108

D-saccharic acid-1,4-lactone ameliorates alloxan-induced diabetes mellitus and oxidative stress in rats through inhibiting pancreatic beta-cells from apoptosis via mitochondrial dependent pathway  

SciTech Connect

Oxidative stress plays a vital role in diabetic complications. To suppress the oxidative stress mediated damage in diabetic pathophysiology, a special focus has been given on naturally occurring antioxidants present in normal diet. D-saccharic acid 1,4-lactone (DSL), a derivative of D-glucaric acid, is present in many dietary plants and is known for its detoxifying and antioxidant properties. The aim of the present study was to evaluate the beneficial role of DSL against alloxan (ALX) induced diabetes in the pancreas tissue of Swiss albino rats. A dose-dependent study for DSL (20-120 mg/kg body weight) was carried out to find the effective dose of the compound in ALX-induced diabetic rats. ALX exposure elevated the blood glucose, glycosylated Hb, decreased the plasma insulin and disturbed the intra-cellular antioxidant machineries whereas oral administration of DSL at a dose of 80 mg/kg body weight restored these alterations close to normal. Investigating the mechanism of the protective activity of DSL we observed that it prevented the pancreatic {beta}-cell apoptosis via mitochondria-dependent pathway. Results showed decreased mitochondrial membrane potential, enhanced cytochrome c release in the cytosol and reciprocal regulation of Bcl-2 family proteins in the diabetic rats. These events were also found to be associated with increased level of Apaf-1, caspase 9, and caspase 3 that ultimately led to pancreatic {beta}-cell apoptosis. DSL treatment, however, counteracted these changes. In conclusion, DSL possesses the capability of ameliorating the oxidative stress in ALX-induced diabetes and thus could be a promising approach in lessening diabetic complications. Highlights: Black-Right-Pointing-Pointer Oxidative stress is suggested as a key event in the pathogenesis of diabetes. Black-Right-Pointing-Pointer D-saccharic acid 1,4-lactone (DSL) reduces the alloxan-induced diabetes mellitus. Black-Right-Pointing-Pointer DSL normalizes cellular antioxidant machineries disturbed due to alloxan toxicity. Black-Right-Pointing-Pointer DSL inhibits pancreatic {beta}-cells apoptosis via mitochondria-dependent pathway. Black-Right-Pointing-Pointer DSL could be a promising approach for the treatment of diabetes mellitus.

Bhattacharya, Semantee [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India)] [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Manna, Prasenjit [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India)] [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India); Gachhui, Ratan [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India)] [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India)

2011-12-15

109

Anti-hyperglycemic and anti-oxidative effect of aqueous extract of Momordica charantia pulp and Trigonella foenum graecum seed in alloxan-induced diabetic rats.  

PubMed

Diabetes is an oxidative stress disorder and oxidative damage to tissues such as heart, kidney, liver and other organs may be a contributory factor to several diabetic complications. Momordica charantia (family: Cucurbitaceae) and Trigonella foenum graecum (family: Fabaceae) are used traditionally in Indian folk medicine to manage diabetes mellitus. In the present study, the anti-hyperglycemic and anti-oxidative potential of aqueous extracts of M. charantia pulp and seed powder of T. foenum graecum were assessed in alloxan (150 mg/kg body weight) induced diabetic rats. Alloxan treatment to the rats could induce diabetes as the fasting blood glucose (FBG) levels were > 280 mg/dl. Treatment of diabetic rats for 30 days with M. charantia and T. foenum graecum could significantly (p < 0.001) improve the FBG levels to near normal glucose levels. Antioxidant activities (superoxide dismutase, catalase, reduced glutathione content and glutathione-s-transferase) and lipid peroxidation levels were measured in heart, kidney and liver tissues of normal, diabetic and experimental animals (diabetics + treatment). TBARS levels were significantly (p < 0.001) higher and anti-oxidative activities were found low in diabetic group, as compared to the control group. Significant (p < 0.001) improvement in both the TBARS levels and antioxidant activities were observed when M. charantia and T. foenum graecum were given to diabetic rats. Our results clearly demonstrate that M. charantia and T. foenum graecum are not only useful in controlling the blood glucose levels, but also have antioxidant potential to protect vital organs such as heart and kidney against damage caused due to diabetes induced oxidative stress. PMID:21174950

Tripathi, Uma Nath; Chandra, Deepak

2010-08-01

110

Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis  

SciTech Connect

Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120 mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markers and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NF?B in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NF?B translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Highlights: ? Taurine controls blood glucose via protection of pancreatic ? cells in diabetic rat. ? Taurine controls blood glucose via increasing the insulin level in diabetic rat. ? Taurine improves cardiac AKT/GLUT4 signaling pathways in diabetic conditions. ? Taurine exerts antioxidant, antihyperlipidemic and antiinflammatory activities. ? It protects cardiac apoptosis by regulating Bcl2 family and caspase 9/3 proteins.

Das, Joydeep; Vasan, Vandana; Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in

2012-01-15

111

Inhibition of carbohydrate and lipid digestive enzymes activities by Zygophyllum album extracts: effect on blood and pancreas inflammatory biomarkers in alloxan-induced diabetic rats.  

PubMed

Zygophyllum album has been used as herbal medicine in Southern Tunisia to treat several diseases such as diabetes mellitus. This study is aimed to reveal the mechanisms underlying the antihyperglycemic potential, the anti-inflammatory and the protective hematological proprieties of this plant in diabetic rats. The inhibition of the ?-amylase activity by different solvent-extract fractions of Z. album was tested in vitro. The fraction endowed with the powerful inhibitory activity against ?-amylase was administered to surviving diabetic rats for 30 days. Data from in vitro indicated that each extract from the medicinal plant showed moderate inhibition of ?-amylase enzyme except the ethyl acetate extract which was ineffective. The powerful inhibition was achieved by ethanol extract of Z. album (EZA) with an IC50 of 43.48 ?g/ml as compared to acarbose (Acar) with an IC50 of 14.88 ?g/ml. In vivo, the results showed that EZA decreased the ?-amylase levels in serum, pancreas and intestine of diabetic rats by 40 %, 45 % and 46 %, respectively, associated with considerably reduction in blood glucose rate by 61 %. Moreover, the EZA helped to protect the structure and function of the ?-cells. Interestingly, EZA had a potent anti-inflammatory effect which is manifested by decreases in CRP and TNF-? levels. Overall, a notable reduction in lipase activity both in serum and small intestine of treated diabetic rats resulted in the improvement of serum and liver lipids profile. Z. album showed a prominent antidiabetic effect via inhibition of carbohydrate and lipid digestive enzymes and ameliorated the inflammation and the disturbance of hematological biomarkers in diabetes. PMID:23996134

Mnafgui, Kais; Kchaou, Mouna; Hamden, Khaled; Derbali, Fatma; Slama, Sadok; Nasri, Mbarek; Salah, Hichem Ben; Allouche, Noureddine; Elfeki, Abdelfattah

2014-03-01

112

Evaluation of Mallotus oppositifolius Methanol Leaf Extract on the Glycaemia and Lipid Peroxidation in Alloxan-Induced Diabetic Rats: A Preliminary Study  

PubMed Central

Objective. Mallotus oppositifolius (Geiseler) Müll. Arg. (Euphorbiaceae) is folklorically used to “treat” diabetic conditions in some parts of Nigeria therefore the study, to investigate the extract of the leaves for activities on hyperglycaemia, lipid peroxidation, and increased cholesterol levels in vivo in alloxan diabetic rats as well as its potential antioxidant activity in vitro. Methods. Albino rats (240–280?g) were given an injection of 120?mg/kg body weight, i.p. of alloxan monohydrate. After 8 days, diabetic animals with elevated fasting blood glucose levels (>9?mmol/L) were considered and selected for the study. Results. Oral treatment with the extract administered every 12?h by gavage at doses of 100, 200, and 400?mg/kg of the extract to the test rats, for 14 days, resulted in a significant dose-dependent decrease in blood glucose levels from 12.82 ± 1.02?mmol/dL to 4.92 ± 2.01?mmol/dL at the highest dose of 400?mg/kg compared to the control drug and glibenclamide as well as attendant significant decline in diabetic rats employed in the study. Conclusion. The extract also showed in vitro concentration-dependent antioxidant activity following the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric reducing assays. Findings further suggest the presence of active antidiabetic and antioxidant principles in M. oppositifolius leaves. PMID:24224091

Nwaehujor, C. O.; Ezeigbo, I. I.; Nwinyi, F. C.

2013-01-01

113

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

PubMed

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. PMID:23859956

Oršoli?, Nada; Sirovina, Damir; Gajski, Goran; Garaj-Vrhovac, Vera; Jazvinš?ak Jembrek, Maja; Kosalec, Ivan

2013-09-18

114

Diabetes attenuates the inhibitory effects of endomorphin-2, but not endomorphin-1 on gastrointestinal transit in mice.  

PubMed

Diabetes affects the entire gastrointestinal tract from the esophagus to the anus. In the present study, the charcoal meal test was undertaken to evaluate and compare the effects of intracerebroventricular (i.c.v.) administration of endomorphins (EMs) on gastrointestinal transit in non-diabetic and diabetic mice. Significantly delayed gastrointestinal transit was found in both 4 and 8 weeks alloxan-induced diabetes compared to non-diabetes. Moreover, i.c.v. EM-1 and EM-2 dose-dependently delayed gastrointestinal transit in non-diabetes and diabetes. The EM-1-induced inhibitory effects of gastrointestinal transit in 4 weeks diabetes were qualitatively similar to those of non-diabetes. However, at higher doses, the EM-1-induced effects in 8 weeks diabetes were largely enhanced. Different to EM-1, the EM-2-induced inhibition of gastrointestinal transit in diabetic mice was significantly attenuated compared to non-diabetic mice. Moreover, these effects were further decreased in 8 weeks diabetes. The delayed gastrointestinal transit effects caused by EM-1 may be primarily mediated by ?2-opioid receptor in both non-diabetes and 4 weeks diabetes. Interestingly, in 8 weeks diabetes, these effects were mediated by ?2- and ?-receptors. However, the inhibitory effects of EM-2 were mediated by ?1-opioid receptor, which exerted a reduced function in diabetes. Also, poor blood glucose control might result in the attenuated effects of EM-2. Our present results demonstrated that diabetes attenuates the inhibitory effects of EM-2, but not EM-1 on gastrointestinal transit in mice. The different effects of EM-1 and EM-2 on gastrointestinal transit in diabetes may be due to changes of opioid receptor subtypes and their functional responses. PMID:24876054

Wang, Chang-lin; Diao, Yu-xiang; Xiang, Qiong; Ren, Yu-kun; Gu, Ning

2014-09-01

115

Protective mechanism of reduced water against alloxan-induced pancreatic beta-cell damage: Scavenging effect against reactive oxygen species.  

PubMed

Reactive oxygen species (ROS) cause irreversible damage to biological macromolecules, resulting in many diseases. Reduced water (RW) such as hydrogen-rich electrolyzed reduced water and natural reduced waters like Hita Tenryosui water in Japan and Nordenau water in Germany that are known to improve various diseases, could protect a hamster pancreatic beta cell line, HIT-T15 from alloxan-induced cell damage. Alloxan, a diabetogenic compound, is used to induce type 1 diabetes mellitus in animals. Its diabetogenic effect is exerted via the production of ROS. Alloxan-treated HIT-T15 cells exhibited lowered viability, increased intracellular ROS levels, elevated cytosolic free Ca(2+) concentration, DNA fragmentation, decreased intracellular ATP levels and lowering of glucose-stimulated release of insulin. RW completely prevented the generation of alloxan-induced ROS, increase of cytosolic Ca(2+) concentration, decrease of intracellular ATP level, and lowering of glucose-stimulated insulin release, and strongly blocked DNA fragmentation, partially suppressing the lowering of viability of alloxan-treated cells. Intracellular ATP levels and glucose-stimulated insulin secretion were increased by RW to 2-3.5 times and 2-4 times, respectively, suggesting that RW enhances the glucose-sensitivity and glucose response of beta-cells. The protective activity of RW was stable at 4 degrees C for over a month, but was lost by autoclaving. These results suggest that RW protects pancreatic beta-cells from alloxan-induced cell damage by preventing alloxan-derived ROS generation. RW may be useful in preventing alloxan-induced type 1-diabetes mellitus. PMID:19003114

Li, Yuping; Nishimura, Tomohiro; Teruya, Kiichiro; Maki, Tei; Komatsu, Takaaki; Hamasaki, Takeki; Kashiwagi, Taichi; Kabayama, Shigeru; Shim, Sun-Yup; Katakura, Yoshinori; Osada, Kazuhiro; Kawahara, Takeshi; Otsubo, Kazumichi; Morisawa, Shinkatsu; Ishii, Yoshitoki; Gadek, Zbigniew; Shirahata, Sanetaka

2002-11-01

116

Possible signaling cascades involved in attenuation of alloxan-induced oxidative stress and hyperglycemia in mice by ethanolic extract of Syzygium jambolanum: drug-DNA interaction with calf thymus DNA as target.  

PubMed

We injected alloxan (100 mg/kg b.w.) in mice (Mus musculus) intra-peritoneally to induce hyperglycemia and divided the hyperglycemic mice into two sub-groups: one was fed ethanolic extract of Syzygium jambolanum (EESJ) (20 mg/kg b.w. for 8 weeks) and the other 85% ethyl alcohol ("vehicle"-control). Chromatographic and mass spectroscopic studies of EESJ revealed two principal components, one corresponding to an iridoid glycoside. We estimated blood glucose, glycosylated hemoglobin, glucokinase, and fructosamine and analyzed the expression of marker proteins like insulin, GLUT2, and GLUT4. We also studied anti-oxidant biomarkers like lipid peroxidase, superoxide dismutase, total thiole and catalase. We assayed generation of reactive oxygen species (ROS) and several inflammatory and apoptotic signal proteins like NFkB, IFN?, iNOS, Bcl(2,) Bax, STAT1 and Caspase3. We further evaluated the effects of hyperglycemia on DNA through comet assay and DNA fragmentation study and assessed drug-DNA interaction by comparative analysis of circular dichroism (CD) spectral data and melting temperature profiles (T(m)) of calf thymus DNA treated with or without EESJ. We observed an elevation of all biomarkers for oxidative stress, generation of ROS and activation of NFkB and down regulation in expression of insulin, GLUT2 and glucokinase in hyperglycemic mice. Administration of EESJ reversed these changes. Histo-pathological observations of pancreas, liver and kidney also revealed relevant changes. Data of CD and (T(m)) indicated an interaction of EESJ with calf thymus DNA, indicating change in structure and conformation. Thus, EESJ has anti-oxidant as well as anti-hyperglycemic activities in diabetic mice, and potentially useful in management of hyperglycemia. PMID:21839831

Samadder, Asmita; Chakraborty, Debrup; De, Arnab; Bhattacharyya, Soumya Sundar; Bhadra, Kakali; Khuda-Bukhsh, Anisur Rahman

2011-10-01

117

Protective and curative effects of Cocos nucifera inflorescence on alloxan-induced pancreatic cytotoxicity in rats  

PubMed Central

Objectives: This study was planned to investigate the effects of pre and post-treatment of young inflorescence of Cocos nucifera (CnI) on alloxan-induced diabetic rats. Materials and Methods: Male albino Sprague Dawely rats were divided into five groups of six animals each. Group I was normal control, Group II was diabetic control, Cocos nucifera Inflorescence (CnI) was fed along with diet [20% (w/w)] orally (Group III) for a period of 11 days prior to alloxan injection (150 mg/kg i.p.). The curative effect of CnI was evaluated at the same feeding levels in alloxan-induced diabetic rats (Group IV) for a period of 30 days. The effects of both pretreatment and post-treatment (Group V) were also evaluated. Biochemical parameters such serum glucose, hepatic glycogen, and enzymes involving carbohydrate metabolism (hexokinase, phosphoglucomutase, pyruvate kinase, glucose-6-phosphatase, fructose 1, 6-diphosphatase, glucose-6 phosphate dehydrogenase, and glycogen phosphorylase) were assayed along with pancreatic histopathology. Data were analyzed using one-way analysis of variance followed by Duncan's post hoc multiple variance test. P < 0.05 was considered statistical significant. Results: Diabetic control rats showed significant increase in serum glucose (P < 0.05) and decrease in hepatic glycogen levels (P < 0.05) compared to normal rats, which was reversed to near normal in both CnI pretreated and post-treated rats. Treatment with CnI resulted in significant decrease (P < 0.05) in activities of gluconeogenic enzymes in Group III and IV on compared to the diabetic control group, while glycolytic enzyme activities were improved in these groups. The cytotoxicity of pancreatic islets also ameliorated by treatment with CnI on histopathological examination. Conclusion: The results obtained in the study indicate the protective and curative effects of CnI on alloxan-induced pancreatic cytotoxicity, which is mediated through the regulation of carbohydrate metabolic enzyme activities and islets cell repair. PMID:23112412

Renjith, Raveendran S.; Rajamohan, Thankappan

2012-01-01

118

Diabetic state-induced modifications of succinyl-choline binding mode in the microsomal fractions of mouse skeletal muscles  

SciTech Connect

The skeletal muscles of alloxan-induced diabetic mice and genetically diabetic KK-CA/sup Y/ mice are hypersensitive to a depolarizing blocker, succinylcholine (SuCh) but not to the competitive antagonist, d-tubocurarine (d-TC). The mechanism by which the action of the depolarizing blocker is modified in the diabetic state was investigated on the binding of /sup 14/C-SuCh to the microsomal fraction isolated from mouse skeletal muscles. The Scatchard plot of microsomal preparations from normal ddY mice showed positive cooperativity in SuCh binding, whereas that of the preparations from alloxan-induced diabetic mice as well as genetically diabetic KK-CA/sup Y/ mice lost the positive cooperative interactions. The dissociation constant (K/sub d/) of high affinity site in diabetic muscles was significantly lower than that in non-diabetic ddY muscle. The microsomal fractions from denervated muscles of normal ddY mice maintained weakly positive cooperativity in SuCh binding, and the affinity of SuCh binding in denervated muscles was lower than that of non-denervated muscles. 17 references, 2 figures, 1 table.

Kimura, M.; Kimura, I.; Fujihara, M.; Hoshino, N.

1988-01-01

119

Modeling Type 1 Diabetes in NOD Mice  

E-print Network

Modeling Type 1 Diabetes in NOD Mice Joseph M. Mahaffy Nonlinear Dynamical Systems Group-Keshet Diabetes Oct 2006 ­ p. 2/3 #12;Outline · Biology - Diabetes and Immune Response · Mathematical Model · Bifurcation Analysis · Simulations · Discussion and Conclusions Diabetes Oct 2006 ­ p. 3/3 #12;Glucose

Mahaffy, Joseph M.

120

Potent hypoglycemic effect of Nigerian anti-diabetic medicinal plants.  

PubMed

The objective of this paper was to investigate the phytochemistry and hypoglycemic activities of aqueous extracts of Anisopus mannii, Daniella olivieri, Detarium macrocarpum, Leptedenia hastate and Mimosa invisa, traditionally prescribed for diabetes mellitus. The aqueous extracts were tested for phytochemicals and free radical scavenging activity by the DPPH assay. The antidiabetic tests were performed in normoglycemic and alloxan induced diabetic mice. High intensity of saponins, xanthones, tannins and glycosides were detected in A. mannii, D. macrocarpum and M. invisa, respectively. For the free radical scavenging activity, D. macrocarpum showed the highest activity with an IC50 of 0.027 mg/ml which was 2.1 folds of ascorbic acid. All extracts showed potent hypoglycemic effects in alloxan induced diabetic mice with the highest fasting blood glucose reduction of 70.39 percent in A. mannii which was 1.54 and 0.98 fold of glibenclamide and human insulin, respectively. A. mannii showed the potent hypoglycemic activity which was 1.54 and 0.98 fold of glibenclamide and insulin, respectively. This study confirmed the traditional use of these Nigerian medicinal plants in diabetes treatment. These plants showed high potential for further investigation to novel anti-diabetic drugs. PMID:22754948

Manosroi, Jiradej; Zaruwa, Moses Z; Manosroi, Aranya

2011-01-01

121

I-E+ nonobese diabetic mice develop insulitis and diabetes  

PubMed Central

The development of type I diabetes in the nonobese diabetic (NOD) mouse is under the control of multiple genes, one or more of which is linked to the major histocompatibility complex (MHC). The MHC class II region has been implicated in disease development, with expression of an I-E transgene in NOD mice shown to provide protection from insulitis and diabetes. To examine the effect of expressing an I-E+ or I-E- non-NOD MHC on the NOD background, three I-E+ and three I-E- NOD MHC congenic strains (NOD.H-2i5, NOD.H-2k, and NOD.H-2h2, and NOD.H-2h4, NOD.H-2i7, and NOD.H-2b, respectively) were developed. Of these strains, both I-E+ NOD.H-2h2 and I-E- NOD.H-2h4 mice developed insulitis, but not diabetes. The remaining four congenic strains were free of insulitis and diabetes. These results indicate that in the absence of the NOD MHC, diabetes fails to develop. Each NOD MHC congenic strain was crossed with the NOD strain to produce I-E+ and I-E- F1 mice; these mice thus expressed one dose of the NOD MHC and one dose of a non-NOD MHC on the NOD background. While a single dose of a non-NOD MHC provided a large degree of disease protection to all of the F1 strains, a proportion of I-E+ and I-E- F1 mice aged 5-12 mo developed insulitis and cyclophosphamide-induced diabetes. When I-E+ F1 mice were aged 9-17 mo, spontaneous diabetes developed as well. These data are the first to demonstrate that I-E+ NOD mice develop diabetes, indicating that expression of I-E in NOD mice is not in itself sufficient to prevent insulitis or diabetes. In fact, I-E- F1 strains were no more protected from diabetes than I-E+ F1 strains, suggesting that other non-NOD MHC- linked genes are important in protection from disease. Finally, transfer of NOD bone marrow into irradiated I-E+ F1 recipients resulted in high incidences of diabetes, indicating that expression of non-NOD MHC products in the thymus, in the absence of expression in bone marrow- derived cells, is not sufficient to provide protection from diabetes. PMID:8350054

1993-01-01

122

Ghrelin reverses experimental diabetic neuropathy in mice  

SciTech Connect

Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin {alpha}, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin's effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.

Kyoraku, Itaru; Shiomi, Kazutaka [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)] [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Kangawa, Kenji [Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan)] [Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Nakazato, Masamitsu, E-mail: nakazato@med.miyazaki-u.ac.jp [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)] [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)

2009-11-20

123

Effects of parabiosis of obese with diabetes and normal mice  

Microsoft Academic Search

Summary  Parabiosis of obese (ob\\/ob) with diabetes (db\\u000a2J\\/db2J) mice caused the obese partner to become hypoglycemic, to lose weight and to die of starvation, while no abnormal changes were observed in the diabetes partner. The striking similarity of this response to that observed in normal mice in parabiosis with diabetes mice suggests that obese mice are like normal mice in

D. L. Coleman

1973-01-01

124

Hypoglycemic Effect of Combination of Azadirachta indica A. Juss. and Gynura procumbens (Lour.) Merr. Ethanolic Extracts Standardized by Rutin and Quercetin in Alloxan-induced Hyperglycemic Rats  

PubMed Central

Purpose: Exploration of plant combinations could be an alternative approach for diabetes treatment. The aim of this study is to evaluate the hypoglycemic effect of combination of A. indica and G. procumbens ethanolic extracts in alloxan-induced diabetic rats. Methods: Powder of A. indica and G. procumbens leaves were macerated with ethanol 70%. Determination of rutin in A. indica and quercetin in G. procumbens were performed by TLC-densitometry. Hyperglycemia in rats was induced by an intraperitoneal injection of alloxan monohydrate at a single dose of 150 mg/kgBW. The rats were treated with 3 dosage variation of combinations for 15 days. Hypoglycemic effect was evaluated by estimating the blood glucose levels and the rats pancreas histological study. Results: A. indica contained 2.90±0.15% of rutin and G. procumbens contained 18.86±0.86% of quercetin. Combination at the ratio of 50mg/kgBW A. indica:112.5mg/kgBW G. procumbens showed the highest hypoglycemic effect: 68.74±4.83% (preprandial) and 73.91±3.18% (postprandial). Histological studies indicated that this combination improved the morphology of the islets of Langerhans and ? cells. It also increased insulin expression and decreased the elevated-glucose concentrations. Conclusion: This study showed that combination of both extracts has better hypoglycemic effect than the single treatment of A. indica or G. procumbens. Combination of both extracts was potential to develop as a blood glucose-lowering agent for diabetic patients.

Sunarwidhi, Anggit Listyacahyani; Sudarsono, Sudarsono; Nugroho, Agung Endro

2014-01-01

125

A new tactic to treat postprandial hyperlipidemia in diabetic rats with gastroparesis by improving gastrointestinal transit  

Microsoft Academic Search

Improvement of gastrointestinal transit was thought to be a new tactic to treat postprandial hypertriglyceridemia in diabetic individuals with gastroparesis. Diabetic gastroparesis, lipid load testing, and the effect of domperidone or aqueous extract of rhizomes of Rheum palmatum L. on postprandial hypertriglyceridemia were evaluated in alloxan-induced diabetic rats. Alloxan diabetic animals had a slow gastrointestinal transit, together with delayed and

Weidong Xie; Dongming Xing; Yunan Zhao; Hui Su; Zhen Meng; Yunyun Chen; Lijun Du

2005-01-01

126

Subacute antidiabetic and in vivo antioxidant effects of methanolic extract of Bridelia micrantha (Hochst Baill) leaf on alloxan-induced hyperglycaemic rats.  

PubMed

The methanolic leaf extract of Bridelia micrantha was tested for subacute antidiabetic and in vivo antioxidant effects in alloxan-induced hyperglycaemic rats. The subacute treatment of the extract (125, 250 and 500 mg/kg) produced 75, 68 and 63% reduction in fasting blood sugar level respectively, on day 14 of treatment. The extract produced time-dependent effect, but did not show a dose-dependent effect. Its optimum antidiabetic activity was noted at the dose of 125 mg/kg and this was comparable to glibenclamide 2 mg/kg (positive control). The extract (125 mg/kg) showed good oral glucose tolerance test (OGTT) effect in both normoglycaemic and hyperglycaemic rats. The OGTT effect of the extract (125 mg/kg) did not differ significantly (p>0.05) from glibenclamide (2 mg/kg). The antioxidant effect of the extract was assayed through the determination of the level of thiobarbituric acid reactive substance (TBARS) and catalase activity. The extract produced a dose-dependent decrease in the serum level of TBARS and gave its optimum catalase activity at the dose of 500 mg/kg. This study suggests that the B. micrantha extract has antihyperglycaemic and antioxidant activities. Therefore, could be a potential source of novel antidiabetic and antioxidant agent for the management of diabetes mellitus. PMID:24760763

Omeh, Yusuf Ndukaku; Onoja, Samuel Okwudili; Ezeja, Maxwell Ikechukwu; Okwor, Peace Obiageli

2014-06-01

127

Exacerbation of Diabetic Renal Alterations in Mice Lacking Vasohibin-1  

PubMed Central

Vasohibin-1 (VASH1) is a unique endogenous inhibitor of angiogenesis that is induced in endothelial cells by pro-angiogenic factors. We previously reported renoprotective effect of adenoviral delivery of VASH1 in diabetic nephropathy model, and herein investigated the potential protective role of endogenous VASH1 by using VASH1-deficient mice. Streptozotocin-induced type 1 diabetic VASH1 heterozygous knockout mice (VASH1+/?) or wild-type diabetic mice were sacrificed 16 weeks after inducing diabetes. In the diabetic VASH1+/? mice, albuminuria were significantly exacerbated compared with the diabetic wild-type littermates, in association with the dysregulated distribution of glomerular slit diaphragm related proteins, nephrin and ZO-1, glomerular basement membrane thickning and reduction of slit diaphragm density. Glomerular monocyte/macrophage infiltration and glomerular nuclear translocation of phosphorylated NF-?B p65 were significantly exacerbated in the diabetic VASH1+/? mice compared with the diabetic wild-type littermates, accompanied by the augmentation of VEGF-A, M1 macrophage-derived MCP-1 and phosphorylation of I?B?, and the decrease of angiopoietin-1/2 ratio and M2 macrophage-derived Arginase-1. The glomerular CD31+ endothelial area was also increased in the diabetic VASH1+/? mice compared with the diabetic-wild type littermates. Furthermore, the renal and glomerular hypertrophy, glomerular accumulation of mesangial matrix and type IV collagen and activation of renal TGF-?1/Smad3 signaling, a key mediator of renal fibrosis, were exacerbated in the diabetic VASH1+/? mice compared with the diabetic wild-type littermates. In conditionally immortalized mouse podocytes cultured under high glucose condition, transfection of VASH1 small interfering RNA (siRNA) resulted in the reduction of nephrin, angiopoietin-1 and ZO-1, and the augmentation of VEGF-A compared with control siRNA. These results suggest that endogenous VASH1 may regulate the development of diabetic renal alterations, partly via direct effects on podocytes, and thus, a strategy to recover VASH1 might potentially lead to the development of a novel therapeutic approach for diabetic nephropathy. PMID:25255225

Hinamoto, Norikazu; Maeshima, Yohei; Yamasaki, Hiroko; Nasu, Tatsuyo; Saito, Daisuke; Watatani, Hiroyuki; Ujike, Haruyo; Tanabe, Katsuyuki; Masuda, Kana; Arata, Yuka; Sugiyama, Hitoshi; Sato, Yasufumi; Makino, Hirofumi

2014-01-01

128

Docosahexaenoic acid has an anti-diabetic effect in streptozotocin-induced diabetic mice  

PubMed Central

Consumption of fish oil-rich foods containing docosahexaenoic acid (DHA) can result in a low incidence of diabetes. The underlying mechanisms of these anti-hyperglycemic effects are ambiguous. This study aims to investigate the role of DHA in the prevention and treatment of type 1 diabetes in a murine model. Forty streptozotocin-induced diabetic mice were divided into control with diabetes, diabetes prevention (500 ?g/kg DHA orally for 5 days) or diabetes treatment groups (DHA solvent in DMSO into the colon for 5 days). The groups were observed for 25 days after administration of DHA. Mice in the prevention and treatment group had shinier fur, increased body weight, significantly lower food and water intake and were more active compared with the control group with diabetes. Elevated insulin and liver SOD and T-AOC levels were also observed. Furthermore, islet cell apoptosis was reduced and islet cell GLP-1R expression increased. PMID:25356177

Li, Ping; Zhang, Li; Tian, Xin; Xing, Jie

2014-01-01

129

IFN-{gamma} gene expression in pancreatic islet-infiltrating mononuclear cells correlates with autoimmune diabetes in nonobese diabetic mice  

SciTech Connect

Insulin-dependent diabetes mellitus in nonobese diabetic (NOD) mice results from selective destruction of pancreatic islet {beta}-cells following islet filtration by mononuclear leukocytes. Cytokines produced by islet-infiltrating mononuclear cells may be involved in {beta}-cell destruction. Therefore, we analyzed cytokine mRNA expression, by reverse-transcriptase PCR (RT-PCR) assay, in mononuclear leukocytes isolated from pancreatic islets of four groups of mice: diabetes-prone female NOD mice; female NOD mice protected from diabetes by injection of CFA at an early age; male NOD mice with a low diabetes incidence; and female BALB/c mice that do not develop diabetes. We found that mRNA levels of IL-1{beta}, IL-2, IL-4, IL-10, and IFN-{gamma} in mononuclear cells from islets of diabetes-prone female NOD mice increased progressively as these cells infiltrated the islets from age 5 wk to diabetes onset (>13 wk). However, only IFN-{gamma} mRNA levels were significantly higher in islet mononuclear cells from 12-wk-old diabetes-prone female NOD mice than from less diabetes-prone NOD mice (CFA-treated females, and males) and normal mice (BALB/c). In contrast, IL-4 mRNA levels were lower in islet mononuclear cells from diabetes-prone female NOD mice than from NOD mice with low diabetes incidence (CFA-treated females and males). Splenic cell mRNA levels of IFN-{gamma} and IL-4 were not different in the four groups of mice. These results suggest that islet {beta}-cell destruction and diabetes in female NOD mice are dependent upon intra-islet IFN-{gamma} production by mononuclear cells, and that CFA-treated female NOD mice and male NOD mice may be protected from diabetes development by down-regulation of IFN-{gamma} production in the islets. 56 refs., 4 figs., 3 tabs.

Rabinovitch, A.; Suarez-Pinzon, W.L.; Sorensen, O. [Univ. of Alberta, Edmonton (Canada)] [and others

1995-05-01

130

Histological changes in the retina in experimental alloxan-induced diabetes in rabbits.  

PubMed

Mature rabbits were given a single dose of alloxan at the dose of 100 mg/kg of b.m. After 3 and 6 weeks and after 3 and 6 months the retina samples were taken from the areas immediate to the papilla of the optic nerve. Half-thin sections were stained with Swiss blue and azure, and the changes in the particular layers were evaluated under the light microscope. Morphological changes in the form of decreased number of neurones (especially ganglionic) and narrowed layer of rods and cones occurred after 6 weeks. After 3 months even further increase in the number of neurones and atrophy of the pigmented epithelium cells were observed. After 6 weeks nearly total atrophy of ganglionic neurones and distinct narrowing of all the layers were found. PMID:11977369

Zarebska, A; Czerny, K; Bakiera, K; Cichacz-Kwiatkowska, B; Lis-Sochocka, M; Ki?, G; Wójtowicz, Z

2001-01-01

131

Anti-diabetic effects of electrolyzed reduced water in streptozotocin-induced and genetic diabetic mice.  

PubMed

Oxidative stress is produced under diabetic conditions and is likely involved in progression of pancreatic beta-cell dysfunction found in diabetes. 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 two different diabetic animal models. The genetically diabetic mouse strain C57BL/6J-db/db (db/db) and streptozotocin (STZ)-induced diabetic mouse were used as insulin deficient type 1 and insulin resistant type 2 animal model, respectively. ERW, provided as a drinking water, significantly reduced the blood glucose concentration and improved glucose tolerance in both animal models. However, ERW fail to affect blood insulin levels in STZ-diabetic mice whereas blood insulin level was markedly increased in genetically diabetic db/db mice. This improved blood glucose control could result from enhanced insulin sensitivity, as well as increased insulin release. The present data suggest that ERW may function as an orally effective anti-diabetic agent and merit further studies on its precise mechanism. PMID:16945392

Kim, Mi-Ja; Kim, Hye Kyung

2006-11-10

132

Evaluation of traditional plant treatments for diabetes: Studies in streptozotocin diabetic mice  

Microsoft Academic Search

Summary  Seven plants and a herbal mixture used for traditional treatment of diabetes were studied in streptozotocin diabetic mice.\\u000a The treatments were supplied as 6.25% by weight of the diet for 9 days. Consumption of diets containing bearberry (Arctostaphylos uva-ursi), golden seal (Hydrastis canadensis), mistletoe (Viscum album) and tarragon (Artemisia dracunculus) significantly reduced the hyperphagia and polydipsia associated with streptozotocin diabetes,

Sara K. Swanston-Flatt; Caroline Day; Clifford J. Bailey; Peter R. Flatt

1989-01-01

133

Role of ITGAE in the development of autoimmune diabetes in non-obese diabetic mice.  

PubMed

There is compelling evidence that autoreactive CD8(+)T cells play a central role in precipitating the development of autoimmune diabetes in non-obese diabetic (NOD) mice, but the underlying mechanisms remain unclear. Given that ITGAE (CD103) recognizes an islet-restricted ligand (E-cadherin), we postulated that its expression is required for initiation of disease. We herein use a mouse model of autoimmune diabetes (NOD/ShiLt mice) to test this hypothesis. We demonstrate that ITGAE is expressed by a discrete subset of CD8(+)T cells that infiltrate pancreatic islets before the development of diabetes. Moreover, we demonstrate that development of diabetes in Itgae-deficient NOD mice is significantly delayed at early but not late time points, indicating that ITGAE is preferentially involved in early diabetes development. To rule out a potential contribution by closely linked loci to this delay, we treated WT NOD mice beginning at 2 weeks of age through 5 weeks of age with a depleting anti-ITGAE mAb and found a decreased incidence of diabetes following anti-ITGAE mAb treatment compared with mice that received isotype control mAbs or non-depleting mAbs to ITGAE. Moreover, a histological examination of the pancreas of treated mice revealed that NOD mice treated with a depleting mAb were resistant to immune destruction. These results indicate that ITGAE(+) cells play a key role in the development of autoimmune diabetes and are consistent with the hypothesis that ITGAE(+)CD8(+)T effectors initiate the disease process. PMID:25525188

Barrie, Elizabeth S; Lodder, Mels; Weinreb, Paul H; Buss, Jill; Rajab, Amer; Adin, Christopher; Mi, Qing-Sheng; Hadley, Gregg A

2015-03-01

134

Anti-diabetic effects of CTB-APSL fusion protein in type 2 diabetic mice.  

PubMed

To determine whether cholera toxin B subunit and active peptide from shark liver (CTB-APSL) fusion protein plays a role in treatment of type 2 diabetic mice, the CTB-APSL gene was cloned and expressed in silkworm (Bombyx mori) baculovirus expression vector system (BEVS), then the fusion protein was orally administrated at a dose of 100 mg/kg for five weeks in diabetic mice. The results demonstrated that the oral administration of CTB-APSL fusion protein can effectively reduce the levels of both fasting blood glucose (FBG) and glycosylated hemoglobin (GHb), promote insulin secretion and improve insulin resistance, significantly improve lipid metabolism, reduce triglycerides (TG), total cholesterol (TC) and low density lipoprotein (LDL) levels and increase high density lipoprotein (HDL) levels, as well as effectively improve the inflammatory response of type 2 diabetic mice through the reduction of the levels of inflammatory cytokines tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6). Histopathology shows that the fusion protein can significantly repair damaged pancreatic tissue in type 2 diabetic mice, significantly improve hepatic steatosis and hepatic cell cloudy swelling, reduce the content of lipid droplets in type 2 diabetic mice, effectively inhibit renal interstitial inflammatory cells invasion and improve renal tubular epithelial cell nucleus pyknosis, thus providing an experimental basis for the development of a new type of oral therapy for type 2 diabetes. PMID:24633252

Liu, Yunlong; Gao, Zhangzhao; Guo, Qingtuo; Wang, Tao; Lu, Conger; Chen, Ying; Sheng, Qing; Chen, Jian; Nie, Zuoming; Zhang, Yaozhou; Wu, Wutong; Lv, Zhengbing; Shu, Jianhong

2014-03-01

135

Leptin Administration Enhances Islet Transplant Performance in Diabetic Mice  

PubMed Central

Islet transplantation is an effective method to obtain long-term glycemic control for patients with type 1 diabetes, yet its widespread use is limited by an inadequate supply of donor islets. The hormone leptin has profound glucose-lowering and insulin-sensitizing action in type 1 diabetic rodent models. We hypothesized that leptin administration could reduce the dose of transplanted islets required to achieve metabolic control in a mouse model of type 1 diabetes. We first performed a leptin dose-response study in C57Bl/6 mice with streptozotocin (STZ)-induced diabetes to determine a leptin dose insufficient to reverse hyperglycemia. Subsequently, we compared the ability of suboptimal islet transplants of 50 or 125 syngeneic islets to achieve glycemic control in STZ-induced diabetic C57Bl/6 mice treated with or without this dose of leptin. The dose-response study revealed that leptin reverses STZ-induced diabetes in a dose-dependent manner. Supraphysiological leptin levels were necessary to restore euglycemia but simultaneously increased risk of hypoglycemia, and also lost efficacy after 12 days of administration. In contrast, 1 µg/day leptin only modestly reduced blood glucose but maintained efficacy throughout the study duration. We then administered 1 µg/day leptin to diabetic mice that underwent transplantation of 50 or 125 islets. Although these islet doses were insufficient to ameliorate hyperglycemia alone, coadministration of leptin with islet transplantation robustly improved control of glucose and lipid metabolism, without increasing circulating insulin levels. This study reveals that low-dose leptin administration can reduce the number of transplanted islets required to achieve metabolic control in STZ-induced diabetic mice. PMID:23656888

Denroche, Heather C.; Quong, Whitney L.; Bruin, Jennifer E.; Tudurí, Eva; Asadi, Ali; Glavas, Maria M.; Fox, Jessica K.; Kieffer, Timothy J.

2013-01-01

136

Trigonella foenum graecum seed powder protects against histopathological abnormalities in tissues of diabetic rats  

Microsoft Academic Search

Trigonella foenum graecum is a well-known hypoglycemic agent used in traditional Indian medicines. It was previously reported that oral administration of its seed powder for 3 weeks to alloxan diabetic rats stabilized glucose homeostasis and free radical metabolism in liver and kidney. In the present study, we further investigated the effects of 3 weeks alloxan induced diabetes on the histological

Shalini Thakran; M. R. Siddiqui; Najma Z. Baquer

2004-01-01

137

Mitochondrial Dysfunction and Apoptosis in Cumulus Cells of Type I Diabetic Mice  

E-print Network

Mitochondrial Dysfunction and Apoptosis in Cumulus Cells of Type I Diabetic Mice Qiang Wang1 demonstrated in diabetic mice; however, the potential pathways by which maternal diabetes exerts its effects of maternal diabetes on the mitochondrial status in cumulus cells. We found an increased frequency

138

DBA/2J Mice Are Susceptible to Diabetic Nephropathy and Diabetic Exacerbation of IOP Elevation  

PubMed Central

Some pathological manifestations of diabetes in the eye include retinopathy, cataracts and elevated intraocular pressure (IOP). Loss of retinal ganglion cells (RGCs) in non-proliferative stages of diabetic retinopathy and small increases in IOP in diabetic patients has raised the possibility that diabetes affects the development and progression of ocular hypertension and glaucoma. The Ins2Akita mutation is known to cause diabetes and retinopathy on a C57BL/6J (B6) background by as early as 3 months of age. Here, the impact of the Akita mutation on glaucoma was assessed using DBA/2J (D2) mice, a widely used mouse model of ocular hypertension induced glaucoma. In D2.Ins2Akita/+ mice, the contribution of diabetes to vascular permeability, IOP elevation, RGC loss, and glaucoma development was assessed. D2.Ins2Akita/+ mice developed a severe diabetic nephropathy and early mortality between 6–8 months of age. This agrees with previous reports showing that the D2 background is more susceptible to diabetes than the B6 background. In addition, D2.Ins2Akita/+ mice had vascular leakage, astrocyte reactivity and a significant increase in IOP. However no RGC loss and no anterograde axonal transport dysfunction were found at 8.5 months of age. Therefore, our data show that despite severe diabetes and an increased IOP compared to controls, RGCs do not lose axon transport or degenerate. This may be due to a DBA/2J-specific genetic modifier(s) that could provide novel and important avenues for developing new therapies for diabetic retinopathy and possibly glaucoma. PMID:25207540

Soto, Ileana; Howell, Gareth R.; John, Cai W.; Kief, Joseph L.; Libby, Richard T.; John, Simon W. M.

2014-01-01

139

Influence of experimental type 1 diabetes on the pulmonary effects of diesel exhaust particles in mice.  

PubMed

Epidemiologically, exposure to particulate air pollution is associated with increases in morbidity and mortality, and diabetics are especially vulnerable to effects of particles. This study was carried out to determine the respiratory effect of diesel exhaust particles (DEP; 0.4mg/kg) on mice rendered diabetic by the injection of streptozotocin or vehicle (control). Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4mg/kg) or saline. 24h later, the measurement of airway reactivity to methacholine in vivo by a forced oscillation technique showed a significant and dose-dependent increase in airway resistance in non-diabetic mice exposed to DEP versus non-diabetic mice exposed to saline. Similarly, the airway resistance was significantly increased in diabetic mice exposed to DEP versus diabetic mice exposed to saline. Nevertheless, there was no difference in the airway resistance between diabetic and non-diabetic mice after i.t. administration of DEP. Following DEP administration there were neutrophil polymorphs infiltration of pulmonary interalveolar septae and the alveolar spaces with many macrophages containing DEP in both diabetic and non-diabetic mice. Interestingly, apoptotic cells were only found in the examined lung sections from diabetic mice exposed to DEP. Total proteins and albumin concentrations in bronchoalveolar lavage (BAL) fluid, markers for increase of epithelial permeability, were significantly increased in diabetic mice exposed to DEP compared to saline-treated diabetic and DEP-treated non diabetic mice. Superoxide dismutase activity and reduced glutathione concentration in BAL were significantly decreased in diabetic mice exposed to DEP compared to saline-treated diabetic and DEP-treated non diabetic mice. Moreover, tumor necrosis factor ? (TNF?) concentrations were significantly increased in diabetic mice exposed to DEP compared to saline-treated diabetic and DEP-treated non diabetic mice. We conclude that, at the dose and time point investigated, DEP equally increased airway resistance and caused infiltration of inflammatory cells in the lung of both diabetic and non-diabetic mice. However, the occurrence of oxidative stress, the presence lung apoptotic cells and the increase of total proteins, albumin and TNF? in BAL fluid were only seen in DEP-exposed diabetic mice suggesting an increased respiratory susceptibility to particulate air pollution. PMID:23147376

Nemmar, Abderrahim; Al-Salam, Suhail; Subramaniyan, Deepa; Yasin, Javed; Yuvaraju, Priya; Beegam, Sumaya; Ali, Badreldin H

2013-02-27

140

Granzyme B Is Dispensable in the Development of Diabetes in Non-Obese Diabetic Mice  

PubMed Central

Pancreatic beta cell destruction in type 1 diabetes is mediated by cytotoxic CD8+ T lymphoctyes (CTL). Granzyme B is an effector molecule used by CTL to kill target cells. We previously showed that granzyme B-deficient allogeneic CTL inefficiently killed pancreatic islets in vitro. We generated granzyme B-deficient non-obese diabetic (NOD) mice to test whether granzyme B is an important effector molecule in spontaneous type 1 diabetes. Granzyme B-deficient islet antigen-specific CD8+ T cells had impaired homing into islets of young mice. Insulitis was reduced in granzyme B-deficient mice at 70 days of age (insulitis score 0.043±0.019 in granzyme B-deficient versus 0.139±0.034 in wild-type NOD mice p<0.05), but was similar to wild-type at 100 and 150 days of age. We observed a reduced frequency of CD3+CD8+ T cells in the islets and peripheral lymphoid tissues of granzyme B-deficient mice (p<0.005 and p<0.0001 respectively), but there was no difference in cell proportions in the thymus. Antigen-specific CTL developed normally in granzyme B-deficient mice, and were able to kill NOD islet target cells as efficiently as wild-type CTL in vitro. The incidence of spontaneous diabetes in granzyme B-deficient mice was the same as wild-type NOD mice. We observed a delayed onset of diabetes in granzyme B-deficient CD8-dependent NOD8.3 mice (median onset 102.5 days in granzyme B-deficient versus 57.50 days in wild-type NOD8.3 mice), which may be due to the delayed onset of insulitis or inefficient priming at an earlier age in this accelerated model of diabetes. Our data indicate that granzyme B is dispensable for beta cell destruction in type 1 diabetes, but is required for efficient early activation of CTL. PMID:22792290

Mollah, Zia U.; Graham, Kate L.; Krishnamurthy, Balasubramanian; Trivedi, Prerak; Brodnicki, Thomas C.; Trapani, Joseph A.; Kay, Thomas W.; Thomas, Helen E.

2012-01-01

141

Vitamin E and diabetic nephropathy in mice model and humans  

PubMed Central

Diabetes mellitus (DM) is associated with increased oxidative stress due to elevated glucose levels in the plasma. Glucose promotes glycosylation of both plasma and cellular proteins with increased risk for vascular events. Diabetic patients suffer from a higher incidence of cardiovascular complications such as diabetic nephropathy. Haptoglobin (Hp) is an antioxidant plasma protein which binds free hemoglobin, thus preventing heme-iron mediated oxidation. Two alleles exist at the Hp gene locus (1 and 2) encoding three possible Hp genotypes that differ in their antioxidant ability, and may respond differently to vitamin E treatment. Several clinical studies to have shown that Hp 1-1 genotype is a superior antioxidant to the Hp 2-2 genotype and Hp 2-2 genotype is associated with a higher incidence of cardiovascular disease. Vitamin E was found to have beneficial effect in patient and mice with Hp 2-2 genotype. In this review we have summarized the results of our studies in patients with diabetic nephropathy treated with vitamin E and in diabetic mice with different haptoglobin genotypes. PMID:24255894

Farid, Nakhoul; Inbal, Dahan; Nakhoul, Nakhoul; Evgeny, Farber; Miller-Lotan, Rachel; Levy, Andrew P; Rabea, Asleh

2013-01-01

142

Tetrahydroindenoindole inhibits the progression of diabetes in mice  

PubMed Central

Diabetes is characterized by elevated fasting blood glucose (FBG) resulting from improper insulin regulation and/or insulin resistance. Herein we used female C57BL/6J mouse models for type 1 diabetes (streptozotocin [STZ] treatment) and type 2 diabetes (high fat diet) to examine the ability of 4b,5,9b,10-tetrahydroindeno[1,2-b]indole (THII) to intervene in the progression of diabetes. THII (100 ?M in drinking water) significantly diminished and partially reversed the increase in FBG levels produced by STZ. After 10 weeks on a high-fat diet, mice had normal FBG levels, but exhibited fasting hyperinsulemia and loss of glucose tolerance. THII significantly diminished these changes in glucose and insulin. In isolated liver mitochondria, THII inhibited succinate-dependent H2O2 production, while in white adipose tissue, THII inhibited NADPH oxidase-mediated H2O2 production and lipid peroxidation. Without intervention, such oxidative processes might otherwise promote diabetogenesis via inflammatory pathways. THII also increased O2 consumption and lowered respiratory quotient (CO2 produced/O2 consumed) in vivo, indicating a greater utilization of fat for metabolic fuel. Increased metabolic utilization of fat correlated with a decrease in the rate of body weight gain in THII-treated mice fed the high fat diet. We conclude that THII may retard the progression of diabetes via multiple pathways, including the inhibition of oxidative and inflammatory pathways. PMID:18823964

Shertzer, Howard G.; Schneider, Scott N.; Kendig, Eric L.; Clegg, Deborah J.; D’Alessio, David A.; Johansson, Elisabet; Genter, Mary Beth

2009-01-01

143

Altered Metabolic Signature in Pre-Diabetic NOD Mice  

PubMed Central

Altered metabolism proceeding seroconversion in children progressing to Type 1 diabetes has previously been demonstrated. We tested the hypothesis that non-obese diabetic (NOD) mice show a similarly altered metabolic profile compared to C57BL/6 mice. Blood samples from NOD and C57BL/6 female mice was collected at 0, 1, 2, 3, 4, 5, 6, 7, 9, 11, 13 and 15 weeks and the metabolite content was analyzed using GC-MS. Based on the data of 89 identified metabolites OPLS-DA analysis was employed to determine the most discriminative metabolites. In silico analysis of potential involved metabolic enzymes was performed using the dbSNP data base. Already at 0 weeks NOD mice displayed a unique metabolic signature compared to C57BL/6. A shift in the metabolism was observed for both strains the first weeks of life, a pattern that stabilized after 5 weeks of age. Multivariate analysis revealed the most discriminative metabolites, which included inosine and glutamic acid. In silico analysis of the genes in the involved metabolic pathways revealed several SNPs in either regulatory or coding regions, some in previously defined insulin dependent diabetes (Idd) regions. Our result shows that NOD mice display an altered metabolic profile that is partly resembling the previously observation made in children progressing to Type 1 diabetes. The level of glutamic acid was one of the most discriminative metabolites in addition to several metabolites in the TCA cycle and nucleic acid components. The in silico analysis indicated that the genes responsible for this reside within previously defined Idd regions. PMID:22514744

Madsen, Rasmus; Banday, Viqar Showkat; Moritz, Thomas; Trygg, Johan; Lejon, Kristina

2012-01-01

144

Neurobehavioral deficits in db/db diabetic mice  

PubMed Central

Recent clinical studies indicate neurobehavioral disturbances in type-2 diabetics. However, there is paucity of preclinical research to support this concept. The validity of db/db mouse as an animal model to study type-2 diabetes and related complications is known. The present study was designed to investigate comprehensively the db/db mouse behavior as preclinical evidence of type-2 diabetes related major neurobehavioral complications. We tested juvenile (5–6 weeks) and adult (10–11 weeks) db/db mice for behavioral depression in forced swim test (FST), psychosis-like symptoms using pre-pulse inhibition (PPI) test, anxiety behavior employing elevated plus maze (EPM) test, locomotor behavior and thigmotaxis using open field test and working memory deficits in Y-maze test. Both juvenile and adult group db/db mice displayed behavioral despair with increased immobility time in FST. There was an age-dependent progression of psychosis-like symptoms with disrupted PPI in adult db/db mice. In the EPM test, db/db mice were less anxious as observed by increased percent open arms time and entries. They were also hypolocomotive as evident by a decrease in their basic and fine movements. There was no impairment of working memory in the Y-maze test in db/db mice. This is the first report of depression, psychosis-like symptoms and anxiolytic behavior of db/db mouse strain. It is tempting to speculate that this mouse strain can serve as useful preclinical model to study type-2 diabetes related neurobehavioral complications. PMID:20637218

Sharma, Ajaykumar N.; Elased, Khalid M.; Garrett, Teresa L.; Lucot, James B.

2011-01-01

145

Gene Expression Profiles of Nondiabetic and Diabetic Obese Mice Suggest a Role of Hepatic Lipogenic  

E-print Network

Gene Expression Profiles of Nondiabetic and Diabetic Obese Mice Suggest a Role of Hepatic Lipogenic Capacity in Diabetes Susceptibility Hong Lan,1 Mary E. Rabaglia,1 Jonathan P. Stoehr,1 Samuel T. Nadler,1 for the development of type 2 diabetes. We have previously reported that in adipose tissue of obese (ob/ob) mice

Attie, Alan D.

146

Manipulation of CD98 resolves type 1 diabetes in nonobese diabetic mice.  

PubMed

The interplay of CD4(+) and CD8(+) T cells targeting autoantigens is responsible for the progression of a number of autoimmune diseases, including type 1 diabetes mellitus (T1D). Understanding the molecular mechanisms that regulate T cell activation is crucial for designing effective therapies for autoimmune diseases. We probed a panel of Abs with T cell-modulating activity and identified a mAb specific for the H chain of CD98 (CD98hc) that was able to suppress T cell proliferation. The anti-CD98hc mAb also inhibited Ag-specific proliferation and the acquisition of effector function by CD4(+) and CD8(+) T cells in vitro and in vivo. Injection of the anti-CD98hc mAb completely prevented the onset of cyclophosphamide-induced diabetes in NOD mice. Treatment of diabetic NOD mice with anti-CD98hc reversed the diabetic state to normal levels, coincident with decreased proliferation of CD4(+) T cells. Furthermore, treatment of diabetic NOD mice with CD98hc small interfering RNA resolved T1D. These data indicate that strategies targeting CD98hc might have clinical application for treating T1D and other T cell-mediated autoimmune diseases. PMID:22291182

Lian, Gaojian; Arimochi, Hideki; Kitamura, Akiko; Nishida, Jun; Li, Shigen; Kishihara, Kenji; Maekawa, Yoichi; Yasutomo, Koji

2012-03-01

147

Trigonella foenum graecum (fenugreek) seed powder improves glucose homeostasis in alloxan diabetic rat tissues by reversing the altered glycolytic, gluconeogenic and lipogenic enzymes  

Microsoft Academic Search

Trigonella foenum graecum (fenugreek) seed powder has been suggested to have potential antidiabetic effects. The effect of oral administration of Trigonella whole seed powder (5% in the diet) for 21 days on glycolytic, gluconeogenic and NADPlinked lipogenic enzymes were studied in liver and kidney tissues of alloxan-induced diabetic Wistar rats. Diabetic rats were characterised by a 4fold higher blood glucose

Jayadev Raju; Dhananjay Gupta; Araga R. Rao; Pramod K. Yadava; Najma Z. Baquer

2001-01-01

148

Berberine improves kidney function in diabetic mice via AMPK activation.  

PubMed

Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. Effective therapies to prevent the development of this disease are required. Berberine (BBR) has several preventive effects on diabetes and its complications. However, the molecular mechanism of BBR on kidney function in diabetes is not well defined. Here, we reported that activation of AMP-activated protein kinase (AMPK) is required for BBR-induced improvement of kidney function in vivo. AMPK phosphorylation and activity, productions of reactive oxygen species (ROS), kidney function including serum blood urea nitrogen (BUN), creatinine clearance (Ccr), and urinary protein excretion, morphology of glomerulus were determined in vitro or in vivo. Exposure of cultured human glomerulus mesangial cells (HGMCs) to BBR time- or dose-dependently activates AMPK by increasing the thr172 phosphorylation and its activities. Inhibition of LKB1 by siRNA or mutant abolished BBR-induced AMPK activation. Incubation of cells with high glucose (HG, 30 mM) markedly induced the oxidative stress of HGMCs, which were abolished by 5-aminoimidazole-4-carboxamide ribonucleoside, AMPK gene overexpression or BBR. Importantly, the effects induced by BBR were bypassed by AMPK siRNA transfection in HG-treated HGMCs. In animal studies, streptozotocin-induced hyperglycemia dramatically promoted glomerulosclerosis and impaired kidney function by increasing serum BUN, urinary protein excretion, and decreasing Ccr, as well as increased oxidative stress. Administration of BBR remarkably improved kidney function in wildtype mice but not in AMPK?2-deficient mice. We conclude that AMPK activation is required for BBR to improve kidney function in diabetic mice. PMID:25409232

Zhao, Long; Sun, Li-Na; Nie, Hui-Bin; Wang, Xue-Ling; Guan, Guang-Ju

2014-01-01

149

ANTIOXIDANT ACTIVITY OF ALBIZZIA LEBBECK (LINN.) BENTH. IN ALLOXAN DIABETIC RATS  

Microsoft Academic Search

There is an increasing demand for natural anti-diabetic drugs, as continuous oral administration of insulin can culminate in many side effects and toxicity. In our endeavour to formulate some cost-effective herbal medicines for diabetes, we undertook this study to evaluate the antioxidant potential of aqueous extract of Albizzia lebbeck (ALL) in diabetic rats. The oxidative stress in alloxan-induc ed diabetic

C. R. RESMI; M. R. VENUKUMAR; M. S. LATHA

150

Antidiabetic activity of isoquercetin in diabetic KK -Ay mice  

PubMed Central

Background Tartary buckwheat bran is an important natural source of quercetin and isoquercetin. Quercetin and isoquercetin are both powerful ?-glucosidase inhibitors. Although the IC50 of isoquercetin as ?-glucosidase inhibitor was much higher than that of quercetin, the bioavailability of isoquercetin was higher than that of quercetin. Hence, we are interested in the antidiabetic effect of isoquercetin in diabetic KK -Ay mice. Methods The hypoglycemic effect of isoquercetin in a type 2 diabetic animal model (KK-Ay mice) was studied. Isoquercetin was administrated at doses of 50, 100 and 200 mg/kg for 35 days. Results It was found that fasting blood glucose concentration was decreased with the 200 mg/kg group (p < 0.01) the most efficient compared with the diabetic control group. In addition, there was significant decrease in plasma C-peptide, triglyceride, total cholesterol and blood urea nitrogen levels after 35 days. Meanwhile, glucose tolerance was improved, and the immunoreactive of pancreatic islets ?-cells was promoted. Conclusions These results suggest that isoquercetin had a regulative role in blood glucose level and lipids, and improved the function of pancreatic islets. Isoquercetin may be useful in the treatment of type 2 diabetes mellitus. PMID:22133267

2011-01-01

151

Evaluation of traditional plant treatments for diabetes: studies in streptozotocin diabetic mice.  

PubMed

Seven plants and a herbal mixture used for traditional treatment of diabetes were studied in streptozotocin diabetic mice. The treatments were supplied as 6.25% by weight of the diet for 9 days. Consumption of diets containing bearberry (Arctostaphylos uva-ursi), golden seal (Hydrastis canadensis), mistletoe (Viscum album) and tarragon (Artemisia dracunculus) significantly reduced the hyperphagia and polydipsia associated with streptozotocin diabetes, but bayberry (Cinnamomum tamala), meadowsweet (Filipendula ulmaria), senna (Cassia occidentalis) and the herbal mixture did not alter these parameters. Bearberry, mistletoe and tarragon retarded the body weight loss but none of the eight treatments significantly altered plasma glucose or insulin concentrations. These studies suggest that bearberry, golden seal, mistletoe and tarragon may counter some of the symptoms of streptozotocin diabetes without, however, affecting glycemic control. PMID:2750445

Swanston-Flatt, S K; Day, C; Bailey, C J; Flatt, P R

1989-01-01

152

Diet Promotes  Cell Loss by Apoptosis in Prediabetic Nonobese Diabetic Mice  

Microsoft Academic Search

Diet as an environmental factor influences age of onset in models of spontaneous insulin-dependent diabetes mellitus. We reported re- cently that a protein-rich diet accelerated diabetes incidence in nono- bese diabetic (NOD) mice. In the present study, we investigated the effect of diet on b-cells and glucose metabolism in NOD mice before diabetes onset. Three different diets were maintained from

THOMAS LINN; CHRISTINE STRATE; KERSTIN SCHNEIDER

1999-01-01

153

Hypoglycemic effect of DL-aminocarnitine in streptozotocin diabetic mice: inhibition of gluconeogenesis  

Microsoft Academic Search

DL-Aminocarnitine and palmitoyl-DL-aminocarnitine are potent, non-covalent inhibitors of carnitine palmitoyl transferase. In both diabetic and non-diabetic fasted mice, DL-aminocarnitine (0.3 mmol\\/kg) and palmitoyl-DL-aminocarnitine (0.1 mmol\\/kg) decrease the blood concentration of ketone bodies to levels observed in fed control mice. Both carnitine palmitoyltransferase inhibitors also normalize plasma glucose levels in diabetic mice. The hypoglycemic effect is maximal at 8 hours, the

D. L. Jenkins; O. W. Griffith

1986-01-01

154

Impaired response of mature adipocytes of diabetic mice to hypoxia  

SciTech Connect

Adipose tissue contains various cells such as infiltrated monocytes/macrophages, endothelial cells, preadipocytes, and adipocytes. Adipocytes have an endocrine function by secreting adipokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-{alpha}, leptin, and adiponectin. Dysregulation of adipokines in adipose tissues leads to a chronic low-grade inflammation which could result in atherosclerosis, hypertension, and type 2 diabetes. A sustained inflammatory state, which is characterized by prolonged persistence of macrophages and neutrophils, is found in diabetic wounds. In addition, subcutaneous adipocytes are enormously increased in amount clinically in type 2 diabetes. However, the function of subcutaneous adipocytes, which play an important role in injured tissue subjected to hypoxia, has not been well characterized in vitro due to the difficulty of maintaining mature adipocytes in culture using conventional methods because of their buoyancy. In this study, we established a novel in vitro culture method of mature adipocytes by enclosing them in a hyaluronan (HA) based hydrogel to study their role in response to stress such as hypoxia. BrdU labeling and Ki67 immunostaining experiments showed that hydrogel enclosed mature adipocytes proliferate in vitro. Both mRNA and protein expression analyses for hypoxia regulated genes, such as vascular endothelial growth factor (VEGF) and heme oxygenase 1 (HO1), showed that mature adipocytes of wild type mice respond to hypoxia. In contrast, mature adipocytes of diabetic db/db and TallyHo mice did not efficiently respond to hypoxia. Our studies suggest that mature adipocytes are functionally active cells, and their abnormal function to hypoxia can be one of underlining mechanisms in type 2 diabetes.

Hong, Seok Jong, E-mail: seok-hong@northwestern.edu; Jin, Da P.; Buck, Donald W.; Galiano, Robert D.; Mustoe, Thomas A., E-mail: tmustoe@nmh.org

2011-10-01

155

HoxD3 accelerates wound healing in diabetic mice  

SciTech Connect

Poorly healing diabetic wounds are characterized by diminished collagen production and impaired angiogenesis. HoxD3, a homeobox transcription factor that promotes angiogenesis and collagen synthesis, is up-regulated during normal wound repair whereas its expression is diminished in poorly healing wounds of the genetically diabetic (db/db) mouse. To determine whether restoring expression of HoxD3 would accelerate diabetic wound healing, we devised a novel method of gene transfer, which incorporates HoxD3 plasmid DNA into a methylcellulose film that is placed on wounds created on db/db mice. The HoxD3 transgene was expressed in endothelial cells, fibroblasts, and keratinocytes of the wounds for up to 10 days. More importantly, a single application of HoxD3 to db/db mice resulted in a statistically significant acceleration of wound closure compared to control-treated wounds. Furthermore, we also observed that the HoxD3-mediated improvement in diabetic wound repair was accompanied by increases in mRNA expression of the HoxD3 target genes, Col1A1 and beta 3-integrin leading to enhanced angiogenesis and collagen deposition in the wounds. Although HoxD3-treated wounds also show improved re-epithelialization as compared to control db/db wounds, this effect was not due to direct stimulation of keratinocyte migration by HoxD3. Finally, we show that despite the dramatic increase in collagen synthesis and deposition in HoxD3-treated wounds, these wounds showed normal remodeling and we found no evidence of abnormal wound healing. These results indicate that HoxD3 may provide a means to directly improve collagen deposition, angiogenesis and closure in poorly healing diabetic wounds.

Hansen, Scott L.; Myers, Connie A.; Charboneau, Aubri; Young, David M.; and Boudreau, Nancy

2003-12-01

156

Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice.  

PubMed

The effects on glucose homeostasis of eleven plants used as traditional treatments for diabetes mellitus were evaluated in normal and streptozotocin diabetic mice. Dried leaves of agrimony (Agrimonia eupatoria), alfalfa (Medicago sativa), blackberry (Rubus fructicosus), celandine (Chelidonium majus), eucalyptus (Eucalyptus globulus), lady's mantle (Alchemilla vulgaris), and lily of the valley (Convallaria majalis); seeds of coriander (Coriandrum sativum); dried berries of juniper (Juniperus communis); bulbs of garlic (Allium sativum) and roots of liquorice (Glycyrhizza glabra) were studied. Each plant material was supplied in the diet (6.25% by weight) and some plants were additionally supplied as decoctions or infusions (1 g/400 ml) in place of drinking water to coincide with the traditional method of preparation. Food and fluid intake, body weight gain, plasma glucose and insulin concentrations in normal mice were not altered by 12 days of treatment with any of the plants. After administration of streptozotocin (200 mg/kg i.p.) on day 12 the development of hyperphagia, polydipsia, body weight loss, hyperglycaemia and hypoinsulinaemia were not affected by blackberry, celandine, lady's mantle or lily of the valley. Garlic and liquorice reduced the hyperphagia and polydipsia but did not significantly alter the hyperglycaemia or hypoinsulinaemia. Treatment with agrimony, alfalfa, coriander, eucalyptus and juniper reduced the level of hyperglycaemia during the development of streptozotocin diabetes. This was associated with reduced polydipsia (except coriander) and a reduced rate of body weight loss (except agrimony). Alfalfa initially countered the hypoinsulinaemic effect of streptozotocin, but the other treatments did not affect the fall in plasma insulin. The results suggest that certain traditional plant treatments for diabetes, namely agrimony, alfalfa, coriander, eucalyptus and juniper, can retard the development of streptozotocin diabetes in mice. PMID:2210118

Swanston-Flatt, S K; Day, C; Bailey, C J; Flatt, P R

1990-08-01

157

Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice  

SciTech Connect

The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the molecular level, peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and terminal marker protein aP2, as well as the mRNA of GLUT4 were up-regulated by PBE. In mature adipocytes, PBE significantly stimulated the uptake of glucose and the expression of insulin receptor substrate-1 (IRS-1). Furthermore, PBE increased PPAR{gamma} luciferase reporter gene activity in COS-1 cells. Taken together, these results suggest that the in vivo anti-diabetic effect of PBE is mediated by both insulin-like and insulin-sensitizing actions in adipocytes.

Kang, Seong-Il; Jin, Young-Jun [Department of Life Science, Cheju National University, 66 Jejudaehakno, Ara-1 Dong, Jejusi, Jeju 690-756 (Korea, Republic of); Ko, Hee-Chul [Department of Chemistry, Cheju National University, 66 Jejudaehakno, Ara-1 Dong, Jejusi, Jeju 690-756 (Korea, Republic of); Choi, Soo-Youn; Hwang, Joon-Ho [Regional Innovation Center, Cheju National University, 66 Jejudaehakno, Ara-1 Dong, Jejusi, Jeju 690-756 (Korea, Republic of); Whang, Ilson; Kim, Moo-Han; Shin, Hye-Sun; Jeong, Hyung-Bok [Department of Life Science, Cheju National University, 66 Jejudaehakno, Ara-1 Dong, Jejusi, Jeju 690-756 (Korea, Republic of); Kim, Se-Jae [Department of Life Science, Cheju National University, 66 Jejudaehakno, Ara-1 Dong, Jejusi, Jeju 690-756 (Korea, Republic of)], E-mail: sjkim@cheju.ac.kr

2008-08-22

158

Traditional Indian anti-diabetic plants attenuate progression of renal damage in streptozotocin induced diabetic mice.  

PubMed

The purpose of the study was to investigate the effects of daily oral feeding Momordica charantia (MC) (200 mg/kg), Eugenia jambolana (EJ) (200 mg/kg), Mucuna pruriens (MP) (200 mg/kg) and Tinospora cordifolia (TC) extracts for 40 days on blood glucose concentrations and kidney functions in streptozotocin (STZ)-diabetic rats. Plasma glucose levels, body weight, urine volume and urinary albumin levels were monitored on every 10th day over a 40-day period while plasma creatinine levels were assessed at the beginning and end of experiment. Renal hypertrophy was assessed as the ratio between the kidney weight and total body weight. Plasma glucose concentrations in STZ-diabetic mice were reduced by the administration of extracts of MC, EJ, TC and MP by 24.4, 20.84, 7.45 and 9.07%, respectively (P<0.005 for MC, EJ, MP and P<0.05 for TC). Urine volume was significantly higher (P<0.005) in diabetic controls and MC, EJ, MP and TC treatment prevented polyuria (P<0.001, 0.0001, 0.01 and 0.001, respectively). After 10 days of STZ administration urinary albumin levels (UAE) were over 6 fold higher in diabetic controls as compared to normal controls. Treatment with MC, EJ, MP and TC significantly prevented the rise in UAE levels from day 0 to 40 in comparison to diabetic controls (P<0.0001, 0.0001, 0.05, 0.05, respectively). Renal hypertrophy was significantly higher in diabetic controls as compared to non-diabetic controls. MC and EJ partially but significantly (P<0.05) prevented renal hypertrophy as compared to diabetic controls. TC and MP failed to modify renal hypertrophy. Results indicate that these plant drugs should be studied further. PMID:11448544

Grover, J K; Vats, V; Rathi, S S; Dawar, R

2001-08-01

159

Hypoglycaemic action of stevioside and ? barley and brewer's yeast based preparation in the experimental model on mice.  

PubMed

The aim of this study was to investigate influence of the preparation based on barley and brewer's yeast extracts with chromium (BBCr) and stevioside (S) on fasting glycaemia and glycaemia in mice after glucose, adrenalin and alloxan application. The animals were divided into three groups: glucose 500 mgkg(-1) (I); adrenalin 0.2 mgkg(-1)(II) and alloxan 100 mg kg(-1) (III) and into subgroups according to the substance they received: stevioside 20 mg kg(-1) (I-S, II-S, III-S); BBCr 750 mg kg(-1)(I-BBCr, II-BBCr, III-BBCr) and saline 1 ml/100g (III-placebo). Glycaemia was measured before and after 7-day treatment with stevioside or BBCr in the following conditions: fasting, 30 min after glucose load (I) or 45 min after adrenaline load (II). In group III glycaemia was measured before and after 12-day treatment with S, BBCr or placebo and alloxan application (7th, 8th and 10th days of treatment ). BBCr significantly reduced fasting glycaemia in I and II groups and glycaemia values after the glucose load (I-BBCr: 9.20 ± 0.61 vs. 7.42 ± 0.59 mmol/L, p = 0.01). Stevioside significantly reduced glycaemia after the adrenalin load (II-S: 13.45 ± 0.71 vs. 11.65 ± 1.19 mmol/L; p = 0.03). In the III-BBCr glycaemia values did not indicate the development of alloxan-induced diabetes and were significantly lower than in the III-placebo (8.6 ± 3.16 vs. 18.8 ± 5.53 mmol/L; p < 0.05). In conclusion, BBCr caused a significant decrease of fasting glycaemia, significant reduction of glycaemia after glucose load and prevented onset of alloxan-induced diabetes. Stevioside caused the decrease of adrenalin-induced hyperglycaemia. PMID:21342135

Cekic, Vlada; Vasovic, Velibor; Jakovljevic, Vida; Mikov, Momir; Sabo, Ana

2011-02-01

160

Increased Inner Ear Susceptibility to Noise Injury in Mice With Streptozotocin-Induced Diabetes  

PubMed Central

We aimed to investigate the pathophysiology of diabetes-associated hearing impairment in type 1 diabetes using mice with streptozotocin-induced diabetes (C57BL/6J; male). Hearing function was evaluated 1, 3, and 5 months after induction of diabetes (five diabetic and five control animals per time point) using auditory-evoked brain stem responses (ABRs). Mice (four diabetic and four control) were exposed to loud noise (105 dB) 5 months after induction of diabetes. ABRs were measured before and after noise exposure. Cochlear blood flows were measured by laser-Doppler flowmeter. Spiral ganglion cells (SGCs) were counted. Vessel endothelial cells were observed by CD31 immunostaining. Chronologic changes in the ABR threshold shift were not significantly different between the diabetic and control groups. However, vessel walls in the modiolus of the cochleae were significantly thicker in the diabetic group than the control group. Additionally, recovery from noise-induced injury was significantly impaired in diabetic mice. Reduced cochlea blood flows and SGC loss were observed in diabetic mice cochleae after noise exposure. Our data suggest that diabetic cochleae are more susceptible than controls to loud noise exposure, and decreased cochlear blood flow due to sclerosis of the vessels and consequent loss of SGCs are possible mechanisms of hearing impairment in diabetic patients. PMID:22851574

Fujita, Takeshi; Yamashita, Daisuke; Katsunuma, Sayaka; Hasegawa, Shingo; Tanimoto, Hitoshi; Nibu, Ken-ichi

2012-01-01

161

Amelioration of Diabetes and Painful Diabetic Neuropathy by Punica granatum L. Extract and Its Spray Dried Biopolymeric Dispersions  

PubMed Central

Aims. To evaluate the effect of Punica granatum (Pg) rind extract and its spray dried biopolymeric dispersions with casein (F1) or chitosan (F2) against Diabetes mellitus (DM) and diabetic neuropathy (DN). Methods. We measured the acute (6?h) and subacute (8 days) effect of various doses of Pg, F1, and F2 and the active compounds on alloxan-induced DM mouse model. We evaluated DN utilizing latency tests for longer period of time (8 weeks). In addition, the in vivo antioxidant activity was assessed utilizing serum catalase level. Results. The results proved that the highest dose levels of Pg extract, F1, F2 exerted remarkable hypoglycemic activity with 48, 52, and 40% drop in the mice glucose levels after 6 hours, respectively. The tested compounds also improved peripheral nerve function as observed from the latency tests. Bioguided fractionation suggested that gallic acid (GA) was Pg main active ingredient responsible for its actions. Conclusion. Pg extract, F1, F2, and GA could be considered as a new therapeutic potential for the amelioration of diabetic neuropathic pain and the observed in vivo antioxidant potential may be involved in its antinociceptive effect. It is highly significant to pay attention to Pg and GA for amelioration and control of DM and its complications. PMID:24982685

Raafat, K.; Samy, W.

2014-01-01

162

Antihyperglycemic activity of Prunella vulgaris L. in streptozotocin-induced diabetic mice  

Microsoft Academic Search

Prunella vulgaris L. (Labiatae) has been reported to have a wide range of health benefits in oriental medicine. This study for the first time is to examine the antihyperglycemic effects of P. vulgaris in streptozotocin (STZ) - induced diabetic ICR mice (STZ diabetic mice). The effects of P. vulgaris L. aqueous-ethanol extract (PVE) on blood glucose, exogenous insulin sensitivity and

Jie Zheng; Jiguo He; Baoping Ji; Ye Li; Xiaofeng Zhang

2007-01-01

163

Myocardial Adipose Triglyceride Lipase Overexpression Protects Diabetic Mice From the Development of Lipotoxic Cardiomyopathy  

PubMed Central

Although diabetic cardiomyopathy is associated with enhanced intramyocardial triacylglycerol (TAG) levels, the role of TAG catabolizing enzymes in this process is unclear. Because the TAG hydrolase, adipose triglyceride lipase (ATGL), regulates baseline cardiac metabolism and function, we examined whether alterations in cardiomyocyte ATGL impact cardiac function during uncontrolled type 1 diabetes. In genetic (Akita) and pharmacological (streptozotocin) murine models of type 1 diabetes, cardiac ATGL protein expression and TAG content were significantly increased. To determine whether increased ATGL expression during diabetes is detrimental or beneficial to cardiac function, we studied streptozotocin-diabetic mice with heterozygous ATGL deficiency and cardiomyocyte-specific ATGL overexpression. After diabetes, streptozotocin-diabetic mice with heterozygous ATGL deficiency displayed increased TAG accumulation, lipotoxicity, and diastolic dysfunction comparable to wild-type mice. In contrast, myosin heavy chain promoter (MHC)-ATGL mice were resistant to diabetes-induced increases in intramyocardial TAG levels, lipotoxicity, and cardiac dysfunction. Moreover, hearts from diabetic MHC-ATGL mice exhibited decreased reliance on palmitate oxidation and blunted peroxisome proliferator--activated receptor-? activation. Collectively, this study shows that after diabetes, increased cardiac ATGL expression is an adaptive, albeit insufficient, response to compensate for the accumulation of myocardial TAG, and that overexpression of ATGL is sufficient to ameliorate diabetes-induced cardiomyopathy. PMID:23349479

Pulinilkunnil, Thomas; Kienesberger, Petra C.; Nagendran, Jeevan; Waller, Terri J.; Young, Martin E.; Kershaw, Erin E.; Korbutt, Gregory; Haemmerle, Guenter; Zechner, Rudolf; Dyck, Jason R.B.

2013-01-01

164

Novel T-cell inhibiting peptides delay the onset of Type 1 diabetes in non-obese diabetic mice.  

PubMed

The aim of this study was to investigate the effectiveness of immunomodulatory peptides in preventing the spontaneous onset of Type 1 diabetes in NOD mice. Two such peptides, CP and C1, were injected intraperitoneally in NOD mice three times a week starting at two different time points, nine weeks and 11 weeks of age, and blood sugar levels monitored for the development of diabetes. CP was shown to be effective in delaying the onset of diabetes compared to control (P = 0.006). The timing of peptide administration was crucial since delay in treatment did not prevent the onset of diabetes (nine weeks versus 11 weeks of age). C1 was effective in delaying the onset of Type 1 diabetes with borderline significance when given at week 11 (P = 0.05). These findings confirm the efficacy of these peptides in the prevention and possible treatment for Type 1 diabetes and thereby create new opportunities for genetic manipulation. PMID:24630734

Wong, M S; Tso, A; Ali, M; Hawthorne, W J; Manolios, N

2014-06-01

165

Obesity and genetics regulate microRNAs in islets, liver, and adipose of diabetic mice  

E-print Network

Obesity and genetics regulate microRNAs in islets, liver, and adipose of diabetic mice Enpeng Zhao 220 miRNAs in pancreatic islets, adipose tissue, and liver from diabetes-resistant (B6) and diabetes et al. 2008; He and Hannon 2004). Overexpression of miRNAs in human cells has been shown

Attie, Alan D.

166

Susceptible mice: identifying a diabetic nephropathy disease locus using a murine model  

Microsoft Academic Search

Diabetic nephropathy is a common, complex disease with a clear genetic predisposition. Human gene association studies are beginning to bear fruit by identifying gene loci that increase diabetic nephropathy risk. Chua et al. report a similar study in diabetic mice that reveals a major nephropathy locus on chromosome 8. Could this be a human nephropathy gene? Time will tell, but

Frank C Brosius

2010-01-01

167

Treatment of Obese Diabetic Mice With a Heme Oxygenase Inducer Reduces Visceral and Subcutaneous  

E-print Network

to ameliorate the deleterious effects of obesity and the metabolic syndrome associated with cardiovascularTreatment of Obese Diabetic Mice With a Heme Oxygenase Inducer Reduces Visceral and Subcutaneous in a mouse and a rat model of diabetes, would ameliorate insulin resistance, obesity, and diabetes in the ob

Abraham, Nader G.

168

Improved Cutaneous Healing in Diabetic Mice Exposed to Healthy Peripheral Circulation  

Microsoft Academic Search

Impaired repair of skin defects is a major complication of diabetes; yet, the pathophysiology of diabetic (db) wound healing remains largely opaque. Here, we investigate the role of humoral factors in modulating db wound repair by generating chimeric animals through parabiotic joining of wild-type (wt) and diabetic (db\\/db) mice. This strategy allows wounds on healing-deficient db\\/db mice to be exposed

Giorgio Pietramaggiori; Sandra S Scherer; Michael Alperovich; Bin Chen; Dennis P Orgill; Amy J Wagers

2009-01-01

169

Phenotypic Changes in Diabetic Neuropathy Induced by a High-Fat Diet in Diabetic C57Bl/6 Mice  

PubMed Central

Emerging evidence suggests that dyslipidemia is an independent risk factor for diabetic neuropathy (DN) (reviewed by Vincent et al. 2009). To experimentally determine how dyslipidemia alters DN, we quantified neuropathic symptoms in diabetic mice fed a high-fat diet. Streptozotocin-induced diabetic C57BL/6 mice fed a high-fat diet developed dyslipidemia and a painful neuropathy (mechanical allodynia) instead of the insensate neuropathy (mechanical insensitivity) that normally develops in this strain. Nondiabetic mice fed a high-fat diet also developed dyslipidemia and mechanical allodynia. Thermal sensitivity was significantly reduced in diabetic compared to nondiabetic mice, but was not worsened by the high-fat diet. Moreover, diabetic mice fed a high-fat diet had significantly slower sensory and motor nerve conduction velocities compared to nondiabetic mice. Overall, dyslipidemia resulting from a high-fat diet may modify DN phenotypes and/or increase risk for developing DN. These results provide new insight as to how dyslipidemia may alter the development and phenotype of diabetic neuropathy. PMID:22144990

Guilford, B. L.; Ryals, J. M.; Wright, D. E.

2011-01-01

170

Autoimmunity to both proinsulin and IGRP is required for diabetes in nonobese diabetic 8.3 TCR transgenic mice.  

PubMed

T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) induce diabetes in nonobese diabetic (NOD) mice. TCR transgenic mice with CD8(+) T cells specific for IGRP(206-214) (NOD8.3 mice) develop accelerated diabetes that requires CD4(+) T cell help. We previously showed that immune responses against proinsulin are necessary for IGRP(206-214)-specific CD8(+) T cells to expand. In this study, we show that diabetes development is dramatically reduced in NOD8.3 mice crossed to NOD mice tolerant to proinsulin (NOD-PI mice). This indicates that immunity to proinsulin is even required in the great majority of NOD8.3 mice that have a pre-existing repertoire of IGRP(206-214)-specific cells. However, protection from diabetes could be overcome by inducing islet inflammation either by a single dose of streptozotocin or anti-CD40 agonist Ab treatment. This suggests that islet inflammation can substitute for proinsulin-specific CD4(+) T cell help to activate IGRP(206-214)-specific T cells. PMID:18354167

Krishnamurthy, Balasubramanian; Mariana, Lina; Gellert, Shane A; Colman, Peter G; Harrison, Leonard C; Lew, Andrew M; Santamaria, Pere; Thomas, Helen E; Kay, Thomas W H

2008-04-01

171

Influences of crude extract of tea leaves, Camellia sinensis, on streptozotocin diabetic male albino mice  

PubMed Central

Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for diabetes mellitus. The aim of the present study was to investigate the hypoglycemic activity of the crude tea leaves extract on streptozotocin (STZ)-induced diabetic mice. The average body weight of animals with diabetes and their percentage changes of body weight gain after 15 and 30 days were significantly lower than that of the normal control mice. In diabetic mice, supplementation with tea leaves extract decreased the loss of body weight. After 15 and 30 days, significant increases in the levels of serum glucose, triglycerides, cholesterol, creatinine, urea, uric acid, glutamic pyruvic acid transaminase (GPT) and glutamic oxaloacetic acid transaminase (GOT) were noted in STZ-diabetic mice fed with normal diet. Also, the values of total protein in this group were statistically declined after 15 and 30 days. The levels of serum glucose and GPT were significantly elevated after 15 and 30 days in diabetic mice supplemented with tea leaves extract. Moreover, the level of serum GOT was notably increased after 30 days. Insignificant alterations were observed in the levels of serum triglycerides, cholesterol, total protein, creatinine, urea and uric acid in diabetic mice supplemented with tea leaves extract. Thus, the present results have shown that tea leaves extract has the antihyperglycemic, antihyperlipidemic, and antihyperproteinemic effects and consequently may alleviate liver and kidney damage associated with STZ-induced diabetes in mice. PMID:23961092

Al-Attar, Atef M.; Zari, Talal A.

2010-01-01

172

Portulaca oleracea Ameliorates Diabetic Vascular Inflammation and Endothelial Dysfunction in db/db Mice.  

PubMed

Type 2 diabetes is associated with significantly accelerated rates of micro- and macrovascular complications such as diabetic vascular inflammation and endothelial dysfunction. In the present study, we investigated the protective effect of the aqueous extract of Portulaca oleracea L. (AP), an edible plant used as a folk medicine, on diabetic vascular complications. The db/db mice were treated with AP (300?mg/kg/day, p.o.) for 10 weeks, and AP treatment markedly lowered blood glucose, plasma triglyceride, plasma level of LDL-cholesterol, and systolic blood pressure in diabetic db/db mice. Furthermore, AP significantly increased plasma level of HDL-cholesterol and insulin level. The impairment of ACh- and SNP-induced vascular relaxation of aortic rings were ameliorated by AP treatment in diabetic db/db mice. This study also showed that overexpression of VCAM-1, ICAM-1, E-selectin, MMP-2, and ET-1 were observed in aortic tissues of untreated db/db mice, which were significantly suppressed by treatment with AP. We also found that the insulin immunoreactivity of the pancreatic islets remarkably increased in AP treated db/db mice compared with untreated db/db mice. Taken together, AP suppresses hyperglycemia and diabetic vascular inflammation, and prevents the development of diabetic endothelial dysfunction for the development of diabetes and its vascular complications. PMID:22474522

Lee, An Sook; Lee, Yun Jung; Lee, So Min; Yoon, Jung Joo; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

2012-01-01

173

Induction of Diabetes in Aged C57B6 Mice Results in Severe Nephropathy  

PubMed Central

Kidney aging is a slowly progressive process that is postulated to be accelerated by intervening diseases, such as diabetes, due in part to the addition of excessive stress and inflammation from the intervening disease to the underlying aging process. This hypothesis was tested by inducing diabetes with streptozotocin in 18-month-old, aging mice. After 4 months of diabetes, these mice developed severe albuminuria, elevated creatinine levels, and renal lesions including extensive apoptotic cell death, glomerulosclerosis, afferent and efferent hyalinosis, and tubulointerstitial inflammation and fibrosis. These symptoms were associated with elevated oxidative stress. The presence of endoplasmic reticulum (ER) stress in 22-month-old diabetic kidneys resulted in up-regulation of C/EBP homologous protein (CHOP), which may play a role in increasing kidney lesions because CHOP-deficient proximal tubular cells were resistant to ER stress-induced cell death, and CHOP-deficient mice were protected from diabetic nephropathy. Moreover, CHOP-deficient mice did not develop albuminuria as they aged. Inflammation, another key component of progressive diabetic nephropathy, was prominent in 22-month-old diabetic kidneys. The expression of tumor-necrosis factor-? in 22-month-old diabetic kidneys may play a role in inflammation, ER stress, and apoptosis. Thus, diabetes may accelerate the underlying kidney aging process present in old mice. PMID:20363923

Wu, Jin; Zhang, Ruihua; Torreggiani, Massimo; Ting, Adrian; Xiong, Huabao; Striker, Gary E.; Vlassara, Helen; Zheng, Feng

2010-01-01

174

Islet Remodeling in Female Mice with Spontaneous Autoimmune and Streptozotocin-Induced Diabetes  

PubMed Central

Islet alpha- and delta-cells are spared autoimmune destruction directed at beta-cells in type 1 diabetes resulting in an apparent increase of non-beta endocrine cells in the islet core. We determined how islet remodeling in autoimmune diabetes compares to streptozotocin (STZ)-induced diabetes. Islet cell mass, proliferation, and immune cell infiltration in pancreas sections from diabetic NOD mice and mice with STZ-induced diabetes was assessed using quantitative image analysis. Serial sections were stained for various beta-cell markers and Ngn3, typically restricted to embryonic tissue, was only upregulated in diabetic NOD mouse islets. Serum levels of insulin, glucagon and GLP-1 were measured to compare hormone levels with respect to disease state. Total pancreatic alpha-cell mass did not change as autoimmune diabetes developed in NOD mice despite the proportion of islet area comprised of alpha- and delta-cells increased. By contrast, alpha- and delta-cell mass was increased in mice with STZ-induced diabetes. Serum levels of glucagon reflected these changes in alpha-cell mass: glucagon levels remained constant in NOD mice over time but increased significantly in STZ-induced diabetes. Increased serum GLP-1 levels were found in both models of diabetes, likely due to alpha-cell expression of prohormone convertase 1/3. Alpha- or delta-cell mass in STZ-diabetic mice did not normalize by replacement of insulin via osmotic mini-pumps or islet transplantation. Hence, the inflammatory milieu in NOD mouse islets may restrict alpha-cell expansion highlighting important differences between these two diabetes models and raising the possibility that increased alpha-cell mass might contribute to the hyperglycemia observed in the STZ model. PMID:25101835

Plesner, Annette; ten Holder, Joris T.; Verchere, C. Bruce

2014-01-01

175

Calcium Insufficiency Accelerates Type 1 Diabetes in Vitamin D Receptor-Deficient Nonobese Diabetic (NOD) Mice  

PubMed Central

Vitamin D exerts important regulatory effects on the endocrine and immune systems. Autoimmune type 1 diabetes (T1D) development in the inbred NOD mouse strain can be accelerated by vitamin D insufficiency or suppressed by chronic treatment with high levels of 1?,25-dihydroxyvitamin D3. Consequently, a report that T1D development was unaffected in NOD mice genetically lacking the vitamin D receptor (VDR) was unexpected. To further assess this result, the mutant stock was imported to The Jackson Laboratory, backcrossed once to NOD/ShiLtJ, and progeny rederived through embryo transfer. VDR-deficient NOD mice of both sexes showed significant acceleration of T1D. This acceleration was not associated with alterations in immune cells targeting pancreatic ?-cells. Rather, the capacity of ?-cells to produce and/or secrete insulin was severely impaired by the hypocalcaemia developing in VDR-deficient NOD mice fed a standard rodent chow diet. Feeding a high-lactose calcium rescue diet that circumvents a VDR requirement for calcium absorption from the intestine normalized serum calcium levels, restored ?-cell insulin secretion, corrected glucose intolerance, and eliminated accelerated T1D in VDR-deficient NOD mice. These findings suggest that calcium and/or vitamin D supplementation may improve disease outcomes in some T1D-prone individuals that are calcium deficient. PMID:21952242

Driver, John P.; Lamont, Deanna J.; Gysemans, Conny; Mathieu, Chantal

2011-01-01

176

Combined antidiabetic benefits of exenatide and dapagliflozin in diabetic mice  

PubMed Central

The combined glucose-lowering effect of exenatide and dapagliflozin has not yet been studied. We investigated this combination (single-dose or 4-week dosing) in diabetic ob/ob mice. Vehicle-corrected basal glucose showed greater reduction 1?h following exenatide?+?dapagliflozin than with exenatide or dapagliflozin alone, and stayed significantly lower for all groups versus vehicle over 3?h. During an oral glucose tolerance test, glucose excursion (30?min post-dose) was significantly lower for exenatide?+?dapagliflozin versus exenatide or dapagliflozin, or vehicle. Exenatide?+?dapagliflozin and exenatide, but not dapagliflozin alone, reduced glucose excretion over 24?h versus vehicle. After dosing for 4?weeks, exenatide, dapagliflozin and exenatide?+?dapagliflozin similarly decreased haemoglobin A1c (HbA1c). Body weight was reduced only with exenatide or exenatide?+?dapagliflozin. The glomerular filtration rate was similar with exenatide, dapagliflozin and vehicle, and increased with exenatide?+?dapagliflozin. Optimized combinatorial dosing of these antidiabetic agents may provide additive glucose lowering in type 2 diabetes mellitus. PMID:24251534

Tatarkiewicz, K; Polizzi, C; Villescaz, C; D'Souza, L J; Wang, Y; Janssen, S; Parkes, D G

2014-01-01

177

RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice  

PubMed Central

Peripheral neuropathy and insensate limbs and digits cause significant morbidity in diabetic individuals. Previous studies showed that deletion of the receptor for advanced end-glycation products (RAGE) in mice was protective in long-term diabetic neuropathy. Here, we tested the hypothesis that RAGE suppresses effective axonal regeneration in superimposed acute peripheral nerve injury attributable to tissue-damaging inflammatory responses. We report that deletion of RAGE, particularly in diabetic mice, resulted in significantly higher myelinated fiber densities and conduction velocities consequent to acute sciatic nerve crush compared with wild-type control animals. Consistent with key roles for RAGE-dependent inflammation, reconstitution of diabetic wild-type mice with RAGE-null versus wild-type bone marrow resulted in significantly improved axonal regeneration and restoration of function. Diabetic RAGE-null mice displayed higher numbers of invading macrophages in the nerve segments postcrush compared with wild-type animals, and these macrophages in diabetic RAGE-null mice displayed greater M2 polarization. In vitro, treatment of wild-type bone marrow–derived macrophages with advanced glycation end products (AGEs), which accumulate in diabetic nerve tissue, increased M1 and decreased M2 gene expression in a RAGE-dependent manner. Blockade of RAGE may be beneficial in the acute complications of diabetic neuropathy, at least in part, via upregulation of regeneration signals. PMID:23172920

Juranek, Judyta K.; Geddis, Matthew S.; Song, Fei; Zhang, Jinghua; Garcia, Jose; Rosario, Rosa; Yan, Shi Fang; Brannagan, Thomas H.; Schmidt, Ann Marie

2013-01-01

178

The Gut Microbiota Modulates Glycaemic Control and Serum Metabolite Profiles in Non-Obese Diabetic Mice  

PubMed Central

Islet autoimmunity in children who later progress to type 1 diabetes is preceded by dysregulated serum metabolite profiles, but the origin of these metabolic changes is unknown. The gut microbiota affects host metabolism and changes in its composition contribute to several immune-mediated diseases; however, it is not known whether the gut microbiota is involved in the early metabolic disturbances in progression to type 1 diabetes. We rederived non-obese diabetic (NOD) mice as germ free to explore the potential role of the gut microbiota in the development of diabetic autoimmunity and to directly investigate whether the metabolic profiles associated with the development of type 1 diabetes can be modulated by the gut microbiota. The absence of a gut microbiota in NOD mice did not affect the overall diabetes incidence but resulted in increased insulitis and levels of interferon gamma and interleukin 12; these changes were counterbalanced by improved peripheral glucose metabolism. Furthermore, we observed a markedly increased variation in blood glucose levels in the absence of a microbiota in NOD mice that did not progress to diabetes. Additionally, germ-free NOD mice had a metabolite profile similar to that of pre-diabetic children. Our data suggest that germ-free NOD mice have reduced glycaemic control and dysregulated immunologic and metabolic responses. PMID:25390735

Greiner, Thomas U.; Hyötyläinen, Tuulia; Knip, Mikael; Bäckhed, Fredrik; Oreši?, Matej

2014-01-01

179

Ultrastructural changes in the receptor parts of retinal rods in experimental alloxan-induced diabetes in rabbits.  

PubMed

Mature rabbits were administered a single dose of alloxan at the dose 100 mg/kg b.m. After 3 and 6 weeks and after 3 and 6 months, the samples of the retina were taken from the areas immediate to the papilla of the optic nerve. Ultrathin sections were dyed according to the Reynold's method, and the receptive parts of the rods were examined under electron microscope BS-500 Tesla. After 6 weeks following alloxan administration, distinct morphological changes in the form of enlargement of certain discs in the receptive parts of rod cells were observed. After 3 months the majority of the discs was damaged, and after 6 months only single, quite well preserved rod cells were found to be present in the retina. PMID:11977368

Zarebska, A; ?a?cut, M; Bakiera, K; Matejko, E; Czerny, K; Ki?, G; Wójtowicz, Z

2001-01-01

180

Divergent effects of oxytocin treatment of obese diabetic mice on adiposity and diabetes.  

PubMed

Oxytocin has been suggested as a novel therapeutic against obesity, because it induces weight loss and improves glucose tolerance in diet-induced obese rodents. A recent clinical pilot study confirmed the oxytocin-induced weight-reducing effect in obese nondiabetic subjects. Nevertheless, the mechanisms involved and the impact on the main comorbidity associated with obesity, type 2 diabetes, are unknown. Lean and ob/ob mice (model of obesity, hyperinsulinemia, and diabetes) were treated for 2 weeks with different doses of oxytocin, analogues with longer half-life (carbetocin) or higher oxytocin receptor specificity ([Thr4,Gly7]-oxytocin). Food and water intake, body weight, and glycemia were measured daily. Glucose, insulin, and pyruvate tolerance, body composition, several hormones, metabolites, gene expression, as well as enzyme activities were determined. Although no effect of oxytocin on the main parameters was observed in lean mice, the treatment dose-dependently reduced food intake and body weight gain in ob/ob animals. Carbetocin behaved similarly to oxytocin, whereas [Thr4,Gly7]-oxytocin (TGOT) and a low oxytocin dose decreased body weight gain without affecting food intake. The body weight gain-reducing effect was limited to the fat mass only, with decreased lipid uptake, lipogenesis, and inflammation, combined with increased futile cycling in abdominal adipose tissue. Surprisingly, oxytocin treatment of ob/ob mice was accompanied by a worsening of basal glycemia and glucose tolerance, likely due to increased corticosterone levels and stimulation of hepatic gluconeogenesis. These results impose careful selection of the conditions in which oxytocin treatment should be beneficial for obesity and its comorbidities, and their relevance for human pathology needs to be determined. PMID:25157455

Altirriba, Jordi; Poher, Anne-Laure; Caillon, Aurélie; Arsenijevic, Denis; Veyrat-Durebex, Christelle; Lyautey, Jacqueline; Dulloo, Abdul; Rohner-Jeanrenaud, Françoise

2014-11-01

181

Arsenic induces diabetic effects through beta-cell dysfunction and increased gluconeogenesis in mice  

NASA Astrophysics Data System (ADS)

Arsenic as a potential risk factor for type 2 diabetes has been received attention recently. However, the roles of arsenic on development of diabetes are unclear. In this study, we compared the influences of inorganic arsenic (iAs) on normal and diabetic mice by systems toxicology approaches. Although iAs exposure did not change glucose tolerance in normal mice, it caused the pancreatic ?-cell dysfunction and increased gluconeogenesis and oxidative damages in liver. However, iAs exposure worsened the glucose tolerance in diabetic mice, which might be due to increased gluconeogenesis and impairment of pancreatic ?-cell function. It is interesting that iAs exposure could improve the insulin sensitivity based on the insulin tolerance testing by the activation of glucose uptake-related genes and enzymes in normal and diabetic individuals. Our data suggested that iAs exposure could cause pre-diabetic effects by altering the lipid metabolism, gluconeogenesis and insulin secretion in normal individual, and worsen diabetic effects in diabetes individual by these processes. Insulin resistance might be not the reason of diabetic effects caused by iAs, indicating that mechanism of the diabetogenic effects of iAs exposure is different from the mechanism associated with traditional risk factors (such as obesity)-reduced type 2 diabetes.

Liu, Su; Guo, Xuechao; Wu, Bing; Yu, Haiyan; Zhang, Xuxiang; Li, Mei

2014-11-01

182

Kinin receptor agonism restores hindlimb postischemic neovascularization capacity in diabetic mice.  

PubMed

Limb ischemia is a major complication of thromboembolic diseases. Diabetes worsens prognosis by impairing neovascularization. Genetic or pharmacological inactivation of the kallikrein-kinin system aggravates limb ischemia in nondiabetic animals, whereas angiotensin I-converting enzyme/kininase II inhibition improves outcome. The role of kinins in limb ischemia in the setting of diabetes is not documented. We assessed whether selective activation of kinin receptors by pharmacological agonists can influence neovascularization in diabetic mice with limb ischemia and have a therapeutic effect. Selective pseudopeptide kinin B1 or B2 receptor agonists resistant to peptidase action were administered by osmotic minipumps at a nonhypotensive dosage for 14 days after unilateral femoral artery ligation in mice previously rendered diabetic by streptozotocin. Comparison was made with ligatured, nonagonist-treated nondiabetic and diabetic mice. Diabetes reduced neovascularization, assessed by microangiography and histologic capillary density analysis, by roughly 40%. B1 receptor agonist or B2 receptor agonist similarly restored neovascularization in diabetic mice. Neovascularization in agonist-treated diabetic mice was indistinguishable from nondiabetic mice. Both treatments restored blood flow in the ischemic hindfoot, measured by laser-Doppler perfusion imaging. Macrophage infiltration increased 3-fold in the ischemic gastrocnemius muscle during B1 receptor agonist or B2 receptor agonist treatment, and vascular endothelial growth factor (VEGF) level increased 2-fold. Both treatments increased, by 50-100%, circulating CD45/CD11b-positive monocytes and CD34(+)/VEGFR2(+) progenitor cells. Thus, selective pharmacological activation of B1 or B2 kinin receptor overcomes the effect of diabetes on postischemic neovascularization and restores tissue perfusion through monocyte/macrophage mobilization. Kinin receptors are potential therapeutic targets in limb ischemia in diabetes. PMID:25398240

Desposito, Dorinne; Potier, Louis; Chollet, Catherine; Gobeil, Fernand; Roussel, Ronan; Alhenc-Gelas, Francois; Bouby, Nadine; Waeckel, Ludovic

2015-02-01

183

Diabetic nephropathy is markedly enhanced in mice lacking the bradykinin B2 receptor  

Microsoft Academic Search

Type I human diabetics and streptozotocin-induced diabetic mice with higher genetically determined levels of angiotensin-converting enzyme have an increased risk of developing nephropathy. However, previous experiments in mice and computer simulations indicate that modest increases in angiotensin-converting enzyme have minimal effects on blood pressure and angiotensin II levels, although bradykinin decreases significantly, inferring that bradykinin is critical for protecting the

Masao Kakoki; Nobuyuki Takahashi; J. Charles Jennette; Oliver Smithies

2004-01-01

184

Anti-diabetic atherosclerosis effect of Prunella vulgaris in db/db mice with type 2 diabetes.  

PubMed

Diabetes mellitus is the leading cause of vascular complications such as atherosclerosis. This study was designed to investigate whether Prunella vulgaris (APV) would inhibit diabetic atherosclerosis in db/db mice with type 2 diabetes. The db/db mice were treated with high fat/high cholesterol (HFHC) diet and an aqueous extract of APV (100 and 200 mg/kg/day) for eight weeks to examine the long-term effect on metabolic abnormalities and diabetic atherosclerosis. APV treatment markedly lowered blood glucose and systolic blood pressure. The db/db mice experienced an increase in blood urea nitrogen as well as a decrease of creatinine clearance, the latter of which was restored by treatment with APV. Treatment with APV markedly decreased total plasma cholesterol, triglyceride, and LDL-cholesterol and also increased the HDL-cholesterol. In addition, malondialdehyde and TGF-?1 were decreased by treatment of APV. On the other hand, total NO level was decreased in db/db mice. However, the NO level was increased by treatment with APV, suggesting an association with vascular dysfunction. Vascular relaxation of aortic rings by acetylcholine or SNP-inducement was ameliorated by APV in a dose-dependent manner. Damage of vascular intima and hypertrophic of media were observed in db/db mice; however its dysfunction was improved by the treatment of APV. APV treatment significantly reduced the aortic expressions of ICAM-1, VCAM-1, ET-1, and nitrotyrosine. Furthermore, expression of eNOS in aortic was remarkably increased by APV treatment. Taken together, APV suppressed hyperglycemia and diabetic vascular dysfunction in HFHC diet-db/db mice. The present data suggest that Prunella vulgaris may prevent development of diabetic atherosclerosis. PMID:22928826

Hwang, Sun Mi; Kim, Jin Sook; Lee, Yun Jung; Yoon, Jung Joo; Lee, So Min; Kang, Dae Gill; Lee, Ho Sub

2012-01-01

185

Daintain/AIF-1 (Allograft Inflammatory Factor-1) accelerates type 1 diabetes in NOD mice  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Daintain/AIF-1 is over-expressed in the blood of NOD mice suffering from insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 stimulates white blood cell proliferation in NOD mice. Black-Right-Pointing-Pointer Daintain/AIF-1 increases blood glucose levels and triggers type 1 diabetes. Black-Right-Pointing-Pointer Daintain/AIF-1 accelerates insulitis, while its antibody prevents insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 enhances the levels of nitric oxide in the pancreases of NOD mice. -- Abstract: A large body of experimental evidence suggests that cytokines trigger pancreatic {beta}-cell death in type 1 diabetes mellitus. Daintain/AIF-1 (Allograft Inflammatory Factor-1), a specific marker for activated macrophages, is accumulated in the pancreatic islets of pre-diabetic BB rats. In the present study, we demonstrate that daintain/AIF-1 is released into blood and the levels of daintain/AIF-1 in the blood of type 1 diabetes-prone non-obese diabetic (NOD) mice suffering from insulitis are significantly higher than that in healthy NOD mice. When injected intravenously into NOD mice, daintain/AIF-1 stimulates white blood cell proliferation, increases the concentrations of blood glucose, impairs insulin expression, up-regulates nitric oxide (NO) production in pancreases and accelerates diabetes in NOD mice, while the antibody against daintain/AIF-1 delays or prevents insulitis in NOD mice. These results imply daintain/AIF-1 triggers type 1 diabetes probably via arousing immune cells activation and induction of NO production in pancreas of NOD mice.

Zhao, Yan-Ying, E-mail: biozyy@163.com [College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041 (China)] [College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041 (China); Huang, Xin-Yuan [College of Life Science and Technology, Hubei Engineering University, Xiaogan 432000 (China)] [College of Life Science and Technology, Hubei Engineering University, Xiaogan 432000 (China); Chen, Zheng-Wang [Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074 (China)] [Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074 (China)

2012-10-26

186

The Genetic Landscape of Type 2 Diabetes in Mice Susanne M. Clee and Alan D. Attie  

E-print Network

The Genetic Landscape of Type 2 Diabetes in Mice Susanne M. Clee and Alan D. Attie Department of diabetes-related phenotypes. The inbred mouse strains differ in the response of their critical physiological functions, such as insulin sensitivity, insulin secretion, -cell proliferation and survival

Attie, Alan D.

187

Toll-Like Receptor 4 Deficiency Accelerates the Development of Insulin-Deficient Diabetes in Non-Obese Diabetic Mice  

PubMed Central

Background/Objective Toll-like receptors (TLR) mediate the recognition of microbial constituents and stress-induced endogenous ligands by the immune system. They may also be involved in the maintenance or break down of tolerance against autologous antigens. The aim of our investigation was to study the consequence of TLR4 deficiency on the development of insulin-deficient diabetes in the NOD mouse. Methods The TLR4 defect of the C57BL/10ScN mouse was backcrossed onto the NOD background and the effect of TLR4 deficiency on diabetes development was analysed by in vivo and in vitro studies. Results Compared to animals with wildtype TLR4 expression (TLR4+/+), female NOD mice carrying a homozygous TLR4 defect (TLR4?/?), showed significant acceleration of diabetes development, with a younger age at diabetes onset (TLR4+/+ 177±22 d, TLR?/?: 118±21 d; p<0.01). Pancreata of 120 d old TLR4?/? NOD mice revealed increased proportions of islets with advanced stages of immune cell infiltration compared to TLR4+/+ mice (p<0.05). TLR4 deficiency did not affect the susceptibility of islet cells to the beta cell damaging mediators nitric oxide or the inflammatory cytokines tumor necrosis factor alpha, interleukin-1 beta and interferon gamma. The lack of TLR4 further had no effect on the frequency of regulatory T-cells but reduced their capacity to inhibit T-cell proliferation. Conclusions Our findings demonstrate that TLR4 deficiency results in an acceleration of diabetes development and immune cell infiltration of islets in NOD mice. We conclude that TLR4 is involved in the progression of the insulitis process thereby controlling the development of insulin-deficient diabetes in NOD mice. PMID:24086519

Gülden, Elke; Ihira, Masaru; Ohashi, Atsushi; Reinbeck, Anna Lena; Freudenberg, Marina A.; Kolb, Hubert; Burkart, Volker

2013-01-01

188

Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance.  

PubMed

Andrographolide, an active component in traditional anti-diabetic herbal plants, is a diterpenoid lactone isolated from Andrographis paniculata because of its potent anti-inflammatory and hypoglycemic effects. However, the effect of andrographolide on the development of diabetes in autoimmune non-obese diabetic (NOD) mice remains unknown. This study aimed to investigate the protective effects of andrographolide on the development of autoimmune diabetes and clarify the underlying mechanism. NOD mice were randomly divided into four groups and administered with water and andrographolide at 50, 100, and 150mg/kg body weight for four weeks. ICR mice were also selected as the control group. Oral glucose tolerance and histopathological insulitis were examined. Th1/Th2/Th17 cytokine secretion was determined by ELISA. The transcriptional profiles of T-bet, GATA3, and ROR?t in the pancreatic lymphatic node samples derived from the NOD mice were detected by RT-PCR. After four weeks of oral supplementation, andrographolide significantly inhibited insulitis, delayed the onset, and suppressed the development of diabetes in 30-week-old NOD mice in a dose dependent manner. This protective status was correlated with a substantially decreased production of interferon (IFN)-? and interleukin (IL)-2, increased IL-10 and transforming growth factor (TGF)-?, and a reduced IL-17. Andrographolide also increased GATA3 mRNA expression but decreased T-bet and ROR?t mRNA expressions. Our results suggested that andrographolide prevented type 1 diabetes by maintaining Th1/Th2/Th17 homeostasis. PMID:23707775

Zhang, Chengliang; Gui, Ling; Xu, Yanjiao; Wu, Tao; Liu, Dong

2013-08-01

189

Evidence that Cd101 is an autoimmune diabetes gene in nonobese diabetic mice.  

PubMed

We have previously proposed that sequence variation of the CD101 gene between NOD and C57BL/6 mice accounts for the protection from type 1 diabetes (T1D) provided by the insulin-dependent diabetes susceptibility region 10 (Idd10), a <1 Mb region on mouse chromosome 3. In this study, we provide further support for the hypothesis that Cd101 is Idd10 using haplotype and expression analyses of novel Idd10 congenic strains coupled to the development of a CD101 knockout mouse. Susceptibility to T1D was correlated with genotype-dependent CD101 expression on multiple cell subsets, including Foxp3(+) regulatory CD4(+) T cells, CD11c(+) dendritic cells, and Gr1(+) myeloid cells. The correlation of CD101 expression on immune cells from four independent Idd10 haplotypes with the development of T1D supports the identity of Cd101 as Idd10. Because CD101 has been associated with regulatory T and Ag presentation cell functions, our results provide a further link between immune regulation and susceptibility to T1D. PMID:21613616

Rainbow, Daniel B; Moule, Carolyn; Fraser, Heather I; Clark, Jan; Howlett, Sarah K; Burren, Oliver; Christensen, Mikkel; Moody, Val; Steward, Charles A; Mohammed, Javid P; Fusakio, Michael E; Masteller, Emma L; Finger, Erik B; Houchins, J P; Naf, Dieter; Koentgen, Frank; Ridgway, William M; Todd, John A; Bluestone, Jeffrey A; Peterson, Laurence B; Mattner, Jochen; Wicker, Linda S

2011-07-01

190

Influence of Two Different Fluences on Laser Photobiomodulation of Wound Healing in Diabetic and Nondiabetic Mice  

NASA Astrophysics Data System (ADS)

Background: Laser irradiation of wounds in mice and rats was shown in previous studies to stimulate healing but in almost all the studies the wounds were not covered. Purpose: To compare the healing of covered wounds in diabetic and nondiabetic mice and the effect of laser irradiation 660 nm at two different fluences (energy densities). Method: A single wound 5-mm diameter was made on the left flank of forty-seven diabetic and twenty nondiabetic mice and covered with Tegaderm HP dressing (day 1). Wounds were irradiated 660 nm 20 s using a low power (18 mW) or high power (80 mW) laser starting immediately post-wounding for 7 consecutive days, with non-irradiated wounds as controls. Mice were euthanized on day 8, 10 or 14. Wound specimens were cut and stained with haematoxylin and eosin, and examined by light microscopy. Results: Wound healing was impaired in diabetic mice. Tegaderm HP dressing had retarded contraction in a large proportion of diabetic mice (splinted the wounds) and to a lesser extent in nondiabetic mice. Healing of splinted wounds was delayed compared to unsplinted wounds, but laser irradiation at high power stimulated healing by re-epithelization and granulation tissue formation. The fluence of low power laser was estimated to be about 1 J/cm2, while that of the high power laser was 3.7 to 5.0 J/cm2. Conclusion: Laser irradiation of wounds 660 nm with 1 J/cm2 had little effect on healing of wounds in diabetic and nondiabetic mice, whereas irradiation with 3.7 to 5.0 J/cm2 stimulated healing of wounds in diabetic mice most of which were splinted by the dressing.

Peplow, Philip V.; Chung, Tzu-Yun; Baxter, G. David

2011-08-01

191

Intravital imaging of CTLs killing islet cells in diabetic mice  

PubMed Central

Type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing ? cells in the pancreatic islets, which are essentially mini-organs embedded in exocrine tissue. CTLs are considered to have a predominant role in the autoimmune destruction underlying T1D. Visualization of CTL-mediated killing of ? cells would provide new insight into the pathogenesis of T1D, but has been technically challenging to achieve. Here, we report our use of intravital 2-photon imaging in mice to visualize the dynamic behavior of a virally expanded, diabetogenic CTL population in the pancreas at cellular resolution. Following vascular arrest and extravasation, CTLs adopted a random motility pattern throughout the compact exocrine tissue and displayed unimpeded yet nonlinear migration between anatomically nearby islets. Upon antigen encounter within islets, a confined motility pattern was acquired that allowed the CTLs to scan the target cell surface. A minority of infiltrating CTLs subsequently arrested at the ? cell junction, while duration of stable CTL–target cell contact was on the order of hours. Slow-rate killing occurred in the sustained local presence of substantial numbers of effector cells. Collectively, these data portray the kinetics of CTL homing to and between antigenic target sites as a stochastic process at the sub-organ level and argue against a dominant influence of chemotactic gradients. PMID:22133877

Coppieters, Ken; Amirian, Natalie; von Herrath, Matthias

2011-01-01

192

The interaction between IL1? and morphine: possible mechanism of the deficiency of morphine-induced analgesia in diabetic mice  

Microsoft Academic Search

It is known that diabetic mice are less sensitive to the analgesic effect of morphine. Some factor(s) derived from mononuclear cells, e.g. interleukin-1? (IL-1?), may be responsible for the diminished analgesic effect of morphine in diabetic mice. Therefore, we examined direct effects of IL-1?, intracerebroventricularly (i.c.v.), on morphine-induced analgesia, subcutaneously (s.c.), in diabetic and control mice by using the tail-flick

Husamettin Gul; Oguzhan Yildiz; Ahmet Dogrul; Ozgur Yesilyurt; Askin Isimer

2000-01-01

193

A bispecific protein capable of engaging CTLA-4 and MHCII protects non-obese diabetic mice from autoimmune diabetes.  

PubMed

Crosslinking ligand-engaged cytotoxic T lymphocyte antigen-4 (CTLA-4) to the T cell receptor (TCR) with a bispecific fusion protein (BsB) comprised of a mutant mouse CD80 and lymphocyte activation antigen-3 (LAG-3) has been shown to attenuate TCR signaling and to direct T-cell differentiation toward Foxp3(+) regulatory T cells (Tregs) in an allogenic mixed lymphocyte reaction (MLR). Here, we show that antigen-specific Tregs can also be induced in an antigen-specific setting in vitro. Treatment of non-obese diabetic (NOD) female mice between 9-12 weeks of age with a short course of BsB elicited a transient increase of Tregs in the blood and moderately delayed the onset of autoimmune type 1 diabetes (T1D). However, a longer course of treatment (10 weeks) of 4-13 weeks-old female NOD animals with BsB significantly delayed the onset of disease or protected animals from developing diabetes, with only 13% of treated animals developing diabetes by 35 weeks of age compared to 80% of the animals in the control group. Histopathological analysis of the pancreata of the BsB-treated mice that remained non-diabetic revealed the preservation of insulin-producing ?-cells despite the presence of different degrees of insulitis. Thus, a bifunctional protein capable of engaging CTLA-4 and MHCII and indirectly co-ligating CTLA-4 to the TCR protected NOD mice from developing T1D. PMID:23704916

Zhao, Hongmei; Karman, Jozsef; Jiang, Ji-Lei; Zhang, Jinhua; Gumlaw, Nathan; Lydon, John; Zhou, Qun; Qiu, Huawei; Jiang, Canwen; Cheng, Seng H; Zhu, Yunxiang

2013-01-01

194

A Bispecific Protein Capable of Engaging CTLA-4 and MHCII Protects Non-Obese Diabetic Mice from Autoimmune Diabetes  

PubMed Central

Crosslinking ligand-engaged cytotoxic T lymphocyte antigen-4 (CTLA-4) to the T cell receptor (TCR) with a bispecific fusion protein (BsB) comprised of a mutant mouse CD80 and lymphocyte activation antigen-3 (LAG-3) has been shown to attenuate TCR signaling and to direct T-cell differentiation toward Foxp3+ regulatory T cells (Tregs) in an allogenic mixed lymphocyte reaction (MLR). Here, we show that antigen-specific Tregs can also be induced in an antigen-specific setting in vitro. Treatment of non-obese diabetic (NOD) female mice between 9–12 weeks of age with a short course of BsB elicited a transient increase of Tregs in the blood and moderately delayed the onset of autoimmune type 1 diabetes (T1D). However, a longer course of treatment (10 weeks) of 4–13 weeks-old female NOD animals with BsB significantly delayed the onset of disease or protected animals from developing diabetes, with only 13% of treated animals developing diabetes by 35 weeks of age compared to 80% of the animals in the control group. Histopathological analysis of the pancreata of the BsB-treated mice that remained non-diabetic revealed the preservation of insulin-producing ?-cells despite the presence of different degrees of insulitis. Thus, a bifunctional protein capable of engaging CTLA-4 and MHCII and indirectly co-ligating CTLA-4 to the TCR protected NOD mice from developing T1D. PMID:23704916

Jiang, Ji-Lei; Zhang, Jinhua; Gumlaw, Nathan; Lydon, John; Zhou, Qun; Qiu, Huawei; Jiang, Canwen; Cheng, Seng H.; Zhu, Yunxiang

2013-01-01

195

Anti-diabetic effects of rice hull smoke extract on glucose-regulating mechanism in type 2 diabetic mice  

Technology Transfer Automated Retrieval System (TEKTRAN)

The aim of this study is to determine the protective effect of a liquid rice hull smoke extract (RHSE) against type 2 diabetes induced by a high fat diet administered to mice. Dietary administration of 0.5% or 1% RHSE for 7 weeks results in significantly reduced blood glucose and triglyceride and to...

196

NRF2 plays a protective role in diabetic retinopathy in mice  

PubMed Central

Aims/hypothesis Although much is known about the pathophysiological processes contributing to diabetic retinopathy (DR), the role of protective pathways has received less attention. The transcription factor nuclear factor erythroid-2-related factor 2 (also known as NFE2L2 or NRF2) is an important regulator of oxidative stress and also has anti-inflammatory effects. The objective of this study was to explore the potential role of NRF2 as a protective mechanism in DR. Methods Retinal expression of NRF2 was investigated in human donor and mouse eyes by immunohistochemistry. The effect of NRF2 modulation on oxidative stress was studied in the human Müller cell line MIO-M1. Non-diabetic and streptozotocin-induced diabetic wild-type and Nrf2 knockout mice were evaluated for multiple DR endpoints. Results NRF2 was expressed prominently in Müller glial cells and astrocytes in both human and mouse retinas. In cultured MIO-M1 cells, NRF2 inhibition significantly decreased antioxidant gene expression and exacerbated tert-butyl hydroperoxide- and hydrogen peroxide-induced oxidative stress. NRF2 activation strongly increased NRF2 target gene expression and suppressed oxidant-induced reactive oxygen species. Diabetic mice exhibited retinal NRF2 activation, indicated by nuclear translocation. Superoxide levels were significantly increased by diabetes in Nrf2 knockout mice as compared with wild-type mice. Diabetic Nrf2 knockout mice exhibited a reduction in retinal glutathione and an increase in TNF-? protein compared with wild-type mice. Nrf2 knockout mice exhibited early onset of blood–retina barrier dysfunction and exacerbation of neuronal dysfunction in diabetes. Conclusions/interpretation These results indicate that NRF2 is an important protective mechanism regulating the progression of DR and suggest enhancement of the NRF2 pathway as a potential therapeutic strategy. PMID:24186494

Xu, Zhenhua; Wei, Yanhong; Gong, Junsong; Cho, Hongkwan; Park, James K.; Sung, Ee-Rah; Huang, Hu; Wu, Lijuan; Eberhart, Charles; Handa, James T.; Du, Yunpeng; Kern, Timothy S.; Thimmulappa, Rajesh; Barber, Alistair J.; Biswal, Shyam; Duh, Elia J.

2014-01-01

197

CD8+ CD122+ PD-1- effector cells promote the development of diabetes in NOD mice.  

PubMed

It is well established that CD4 and CD8 T cells are required for the initiation of autoimmune diabetes in NOD mice. However, different subsets of CD4 or CD8 cells may play different roles in the initiation of insulitis. In this study, we evaluated the role of the previously described CD8(+) CD122(+) in this process. We found that prediabetic NOD mice have an almost 50% reduction of CD8(+) CD122(+) T cells in their secondary lymphoid organs compared with BL/6 or Balb/c mouse strains. This reduction is explained by the lack of the regulatory CD8(+) CD122(+) PD-1(+) cell population in the NOD mice, as we found that all CD8(+) CD122(+) T cells from prediabetic NOD mice lack PD-1 expression and regulatory function. Depletion of CD8(+) CD122(+) PD-1(-) cells through injection of anti-CD122 mAb in prediabetic female NOD mice reduced the infiltration of mononuclear cells into the Langerhans islets and delayed the onset and decreased the incidence of overt diabetes. In addition, we found that transfer of highly purified and activated CD8(+) CD122(+) PD-1(-) cells, together with diabetogenic splenocytes from NOD donors to NOD SCID recipients, accelerates the diabetes development in these mice. Together, these results demonstrate that CD8(+) CD122(+) PD-1(-) T cells from NOD mice are effector cells that are involved in the pathogenesis of autoimmune diabetes. PMID:25387835

Arndt, Börge; Witkowski, Lukas; Ellwart, Joachim; Seissler, Jochen

2015-01-01

198

Cardiac-Specific Overexpression of CYP2J2 Attenuates Diabetic Cardiomyopathy in Male Streptozotocin-Induced Diabetic Mice  

PubMed Central

Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to biologically active cis-epoxyeicosatrienoic acids, which have potent vasodilatory, antiinflammatory, antiapoptotic, and antidiabetes properties. Here, we showed the effects of cardiac-specific overexpression of CYP epoxygenase 2J2 (CYP2J2) on diabetic cardiomyopathy and insulin resistance in high-fat (HF) diet fed, low-dose streptozotocin-treated mice. Diabetic cardiomyopathy was induced by HF and streptozotocin in cardiac-specific CYP2J2 transgenic mice. Physiological parameters and systemic metabolic parameters were monitored using ELISA kits. Intraperitoneal injection glucose tolerance test and hyperinsulinemic-euglycemic clamp study were implied to indicate insulin resistance. Cardiac function was assessed by echocardiography and Millar catheter system. Real-time PCR and Western blotting were used in signal pathway detection. ?MHC-CYP2J2 transgenic mice showed significantly lower plasma glucose and insulin levels, improved glucose tolerance, and increased cardiac glucose uptake. Furthermore, ?MHC-CYP2J2 transgenic mice were significantly protected from HF-streptozotocin-induced diabetic cardiomyopathy. Strikingly, CYP2J2 overexpression attenuated myocardial hypertrophy induced by diabetes. We conclude that cardiac-specific overexpression of CYP2J2 significantly protects against diabetic cardiomyopathy, which may be due to improved cardiac insulin resistance, glucose uptake, and reversal of cardiac hypertrophy. Relevant mechanisms may include up-regulation of peroxisome proliferator-activated receptor ?, activation of insulin receptor and AMP-activated protein kinase signaling pathways, and inhibition of nuclear factor of activated T cells c3 signal by enhanced atrial natriuretic peptide production. These results suggest that CYP2J2 epoxygenase metabolites likely play an important role in plasma glucose homeostasis, and enhancement of epoxyeicosatrienoic acids activation may serve as an effective therapeutic strategy to prevent diabetic cardiomyopathy. PMID:23696562

Ma, Ben; Xiong, Xiaojv; Chen, Chen; Li, Huaping; Xu, Xizhen; Li, Xuguang; Li, Rui; Chen, Guangzhi; Dackor, Ryan T.; Zeldin, Darryl C.

2013-01-01

199

Ecklonia cava Inhibits Glucose Absorption and Stimulates Insulin Secretion in Streptozotocin-Induced Diabetic Mice  

PubMed Central

Aims of study. Present study investigated the effect of Ecklonia cava (EC) on intestinal glucose uptake and insulin secretion. Materials and methods. Intestinal Na+-dependent glucose uptake (SGU) and Na+-dependent glucose transporter 1 (SGLT1) protein expression was determined using brush border membrane vesicles (BBMVs). Glucose-induced insulin secretion was examined in pancreatic ?-islet cells. The antihyperglycemic effects of EC, SGU, and SGLT1 expression were determined in streptozotocin (STZ)-induced diabetic mice. Results. Methanol extract of EC markedly inhibited intestinal SGU of BBMV with the IC50 value of 345??g/mL. SGLT1 protein expression was dose dependently down regulated with EC treatment. Furthermore, insulinotrophic effect of EC extract was observed at high glucose media in isolated pancreatic ?-islet cells in vitro. We next conducted the antihyperglycemic effect of EC in STZ-diabetic mice. EC supplementation markedly suppressed SGU and SGLT1 abundance in BBMV from STZ mice. Furthermore, plasma insulin level was increased by EC treatment in diabetic mice. As a result, EC supplementation improved postprandial glucose regulation, assessed by oral glucose tolerance test, in diabetic mice. Conclusion. These results suggest that EC play a role in controlling dietary glucose absorption at the intestine and insulinotrophic action at the pancreas contributing blood glucose homeostasis in diabetic condition. PMID:22645628

Kim, Hye Kyung

2012-01-01

200

Protective effect of berberine on serum glucose levels in non-obese diabetic mice.  

PubMed

Among the active components in traditional anti-diabetic herbal plants, berberine which is an isoquinoline alkaloid exhibits promising potential for its potent anti-inflammatory and hypoglycemic effects. However, the berberine effect on serum glucose levels in type 1 diabetes (T1D) subjects still remains unknown. This study investigated berberine's effects on serum glucose levels using non-obese diabetic (NOD) mice that spontaneously develop T1D. The NOD mice were randomly divided into four groups, administered water with 50, 150, and 500 mg berberine/kg bw, respectively, through 14 weeks. ICR mice were also selected as a species control group to compare with the NOD mice. Changes in body weight, oral glucose challenge, and serum glucose levels were determined to identify the protective effect of berberine on T1D. After the 14-week oral supplementation, berberine decreased fasting serum glucose levels in NOD mice close to the levels in normal ICR mice in a dose dependent manner. Serum berberine levels showed a significantly (P<0.05) negative and non-linear correlation with fasting glucose levels in berberine-administered NOD mice. Our results suggested that berberine supplemented at appropriate doses for 14 weeks did not cause toxic side effects, but improved hyperglycemia in NOD mice. PMID:22266065

Chueh, Wei-Han; Lin, Jin-Yuarn

2012-03-01

201

Insulin-like growth factor-1 (IGF-1) protects NOD mice from insulitis and diabetes.  

PubMed Central

To evaluate the effect of IGF-1 on the autoimmune process of beta cell destruction, permissive non-obese diabetic (NOD) recipients were adoptively transferred with 7 x 10(6) autoreactive T cells from diabetic NOD mice and were administered subcutaneously 10 micrograms rhIGF-1, twice daily for 3 weeks. Administration of rhIGF-1 reduced the final incidence of successful transfers of diabetes observed in only 6/24 mice (25%) versus 12/21 (57%) in control mice. A marked reduction of insulitis during histological analysis of pancreatic glands was also observed. Mice treated with rhIGF-1 had a higher percentage of intact islets (48.6 +/- 12% versus 1.6 +/- 1.1%, P = 0.001) and a lower percentage of infiltrated islets. Islets from rhIGF-1-treated mice had a more intense insulin staining reflecting a higher beta cell mass, but no difference was observed in the amount of insulin content of pancreatic extracts and in the amounts of mRNA transcripts for proinsulin. No difference was also observed in the titres of three islet cell antibody (ICA)-positive sera and in the pattern of A2B5 staining. Some mice developed diabetes and severe islet cell infiltration despite rhIGF-1, thus indicating that some committed T cells were still able to invade the islets and cause beta cell destruction. The percentages of CD4+ and CD8+ T cells in the spleen of experimental mice were similar. To evaluate the effects of rhIGF-1 on cell trafficking in recipient mice, T cells from diabetic NOD Thy-1,2 mice injected into congenic NOD-N Thy-1,1 mice were monitored 3 weeks after adoptive cell transfer. The percentage of Thy-1,2+ T cells was significantly reduced in the spleen (10.8 +/- 1.3% versus 17.2 +/- 3.9%, P = 0.004) of rhIGF-1 treated mice in contrast to the thymus (68.4 +/- 7.9% versus 72.87 +/- 6.2%, P = 0.306), suggesting that rhIGF-1 could influence T cell trafficking to the lymphoid organs. The findings that rhIGF-1 has protective effects in autoimmune diabetes opens new perspectives for future experiments as well as for preventive strategies in human type I diabetes. Images Fig. 3 PMID:7586687

Bergerot, I; Fabien, N; Maguer, V; Thivolet, C

1995-01-01

202

Flos Puerariae Extract Prevents Myocardial Apoptosis via Attenuation Oxidative Stress in Streptozotocin-Induced Diabetic Mice  

PubMed Central

Background Diabetic cardiomyopathy (DCM) suggests a direct cellular insult to myocardium. Apoptosis is considered as one of the hallmarks of DCM. Oxidative stress plays a key role in the pathogenesis of DCM. In this study, we explored the prevention of myocardial apoptosis by crude extract from Flos Puerariae (FPE) in experimental diabetic mice. Methods Experimental diabetic model was induced by intraperitoneally injection of streptozotocin (STZ, 50 mg/kg/day) for five consecutive days in C57BL/6J mice. FPE (100, 200 mg/kg) was orally administrated once a day for ten weeks. Cardiac structure changes, apoptosis, superoxide production, NADPH oxidase subunits expression (gp91phox, p47phox, and p67phox), and related regulatory factors were assessed in the heart of mice. Results Diabetic mice were characterized by high blood glucose (?11.1 mmol/L) and reduced body weight. In the end of the experiment, aberrant myofilament structure, as well as TUNEL positive cardiac cells coupled with increased Bax/Bcl-2 ratio and Caspase-3 expression was found in diabetic mice. Moreover, ROS formation, the ratio of NADP+/NADPH and NADPH oxidase subunits expression of gp91phox and p47phox, lipid peroxidation level was significantly increased, while antioxidant enzyme SOD and GSH-Px activity were reduced in the myocardial tissue of diabetic mice. In contrast, treatment with FPE resulted in a normalized glucose and weight profile. FPE administration also preserved myocardial structure and reduced apoptotic cardiac cell death in diabetic mice. The elevated markers of oxidative stress were significantly reversed by FPE supplementation. Further, FPE treatment markedly inhibited the increased Bax/Bcl-2 ratio and Caspase-3 expression, as well as suppressed JNK and P38 MAPK activation in the heart of diabetic mice. Conclusions Our data demonstrate for the first time that FPE may have therapeutic potential for STZ-induced diabetic cardiomyopathy through preventing myocardial apoptosis via attenuation oxidative stress. And this effect is probably mediated by JNK and P38 MAPK signaling pathway. PMID:24865768

Guo, Shuang; Cheng, Hongke; Wu, Jiliang; Liu, Chao

2014-01-01

203

Activation of spinal cannabinoid CB2 receptors inhibits neuropathic pain in streptozotocin-induced diabetic mice.  

PubMed

The role of spinal cannabinoid systems in neuropathic pain of streptozotocin (STZ)-induced diabetic mice was studied. In normal mice, injection of the cannabinoid receptor agonist WIN-55,212-2 (1 and 3?g, i.t.) dose-dependently prolonged the tail-flick latency, whereas there were no changes with the injection of either cannabinoid CB1 (AM 251, 1 ?g, i.t.) or CB2 (AM 630, 4 ?g, i.t.) receptor antagonists. AM 251 (1 ?g, i.t.), but not AM 630 (4 ?g, i.t.), significantly inhibited the prolongation of the tail-flick latency induced by WIN-55,212-2 (3 ?g, i.t.). In STZ-induced diabetic mice, the tail-flick latency was significantly shorter than that in normal mice. A low dose of WIN-55,212-2 (1 ?g, i.t.) significantly recovered the tail-flick latency in STZ-induced diabetic mice. The effect of WIN-55,212-2 (1 ?g, i.t.) in STZ-induced diabetic mice was significantly inhibited by AM 630 (4 ?g, i.t.), but not AM 251 (1 ?g). The selective cannabinoid CB2 receptor agonist L-759,656 (19 and 38 ?g, i.t.) also dose-dependently recovered the tail-flick latency in STZ-induced diabetic mice, and this recovery was inhibited by AM 630 (4 ?g, i.t.). The protein levels of cannabinoid CB1 receptors, CB2 receptors and diacylglycerol lipase ? (DGL-?), the enzyme that synthesizes endocannabinoid 2-arachidonoylglycerol, in the spinal cord were examined using Western blotting. The protein levels of both cannabinoid CB1 and CB2 receptors were increased in STZ-induced diabetic mice, whereas the protein level of DGL-? was significantly decreased. These results indicate that spinal cannabinoid systems are changed in diabetic mice and suggest that cannabinoid CB2 receptor agonists might have an ability to recover diabetic neuropathic pain. PMID:23892011

Ikeda, H; Ikegami, M; Kai, M; Ohsawa, M; Kamei, J

2013-10-10

204

Protective effects of total flavonoids from Flos Puerariae on retinal neuronal damage in diabetic mice  

PubMed Central

Purpose To investigate the potential protective effects of total flavonoids from Flos Puerariae (TFF) on retinal neural cells in diabetic mice. Methods C57BL/6J mice were intraperitoneally injected with streptozotocin to generate type I diabetes in a murine model, as indicated by blood glucose levels ?11.1 mmol/l. TFF was administered intragastrically at a dose of 50, 100, or 200 mg/kg/day. After 10 weeks of administration, the mice were euthanized, and the eyes were dissected. Retinal histology was examined, and the thickness of the retina was measured. Ultrastructural changes in the retinal ganglion cells and capillary basement membrane were observed with electron microscopy. Apoptosis of retinal neural cells was determined with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay. Bax and Bcl-2 expression in the retinal tissues was determined with immunohistochemical staining and western blotting. Results Compared with the diabetic mice, the blood glucose level decreased (p<0.01) and the bodyweight increased (p<0.05) in the 100 and 200 mg/kg TFF-treated groups. The thickness of the retina significantly increased (p<0.01), and the retinal capillary basement membrane (BM) thickness was reduced in the 100 and 200 mg/kg TFF-treated diabetic mice (DM). The 100 and 200 mg/kg TFF treatments also attenuated the diabetes-induced apoptosis of retinal neural cells. Consistent with these effects, TFF treatment decreased the Bax expression level and, concurrently, increased the ratio of Bcl-2 to Bax. Conclusions TFF attenuated diabetes-induced apoptosis in retinal neurons by inhibiting Bax expression and increasing the ratio of Bcl-2 to Bax, which suggests that TFF might prevent retinal neuronal damage in diabetes mellitus. PMID:24146535

Li, Dai; Yang, Fang; Cheng, Hongke; Liu, Chao; Sun, Ming; Wu, Kaili

2013-01-01

205

Augmenting podocyte injury promotes advanced diabetic kidney disease in Akita mice.  

PubMed

To determine if augmenting podocyte injury promotes the development of advanced diabetic nephropathy (DN), we created mice that expressed the enzyme cytosine deaminase (CD) specifically in podocytes of diabetic Akita mice (Akita-CD mice). In these mice, treatment with the prodrug 5-flucytosine (5-FC) causes podocyte injury as a result of conversion to the toxic metabolite 5-fluorouracil (5-FU). We found that treatment of 4-5 week old Akita mice with 5-FC for 5 days caused robust albuminuria at 16 and 20 weeks of age compared to 5-FC treated Akita controls, which do not express CD (Akita CTLs). By 20 weeks of age, there was a significant increase in mesangial expansion in Akita-CD mice compared to Akita CTLs, which was associated with a variable increase in glomerular basement membrane (GBM) width and interstitial fibrosis. At 20 weeks of age, podocyte number was similarly reduced in both groups of Akita mice, and was inversely correlated with the albuminuria and mesangial expansion. Thus, enhancing podocyte injury early in the disease process promotes the development of prominent mesangial expansion, interstitial fibrosis, increased GBM thickness and robust albuminuria. These data suggest that podocytes play a key role in the development of advanced features of diabetic kidney disease. PMID:24491571

Wang, Liming; Tang, Yuping; Eisner, William; Sparks, Matthew A; Buckley, Anne F; Spurney, Robert F

2014-02-21

206

Raxofelast, a hydrophilic vitamin E-like antioxidant, stimulates wound healing in genetically diabetic mice  

Microsoft Academic Search

Background. Impaired wound healing is a well-documented phenomenon in experimental and clinical diabetes. Emerging evidence favors the involvement of free radicals in the pathogenesis of diabetes-related healing deficit. This study assessed the effect of systemic administration of raxofelast, a protective membrane antioxidant agent, on wound healing by using healing-impaired (db\\/db) mice. Methods. The wound healing effect of raxofelast was investigated

Mariarosaria Galeano; Valerio Torre; Barbara Deodato; Giuseppe M. Campo; Michele Colonna; Alessio Sturiale; Francesco Squadrito; Vittorio Cavallari; Domenico Cucinotta; Michele Buemi; Domenica Altavilla

2001-01-01

207

Global Renal Gene Expression Profiling Analysis in B2-Kinin Receptor Null Mice: Impact of Diabetes  

PubMed Central

Diabetic nephropathy (DN), the leading cause of end-stage renal failure, is clinically manifested by albuminuria and a progressive decline in glomerular filtration rate. The risk factors and mechanisms that contribute to the development and progression of DN are still incompletely defined. To address the involvement of bradykinin B2-receptors (B2R) in DN, we used a genome wide approach to study the effects of diabetes on differential renal gene expression profile in wild type and B2R knockout (B2R?/?) mice. Diabetes was induced with streptozotocin and plasma glucose levels and albumin excretion rate (AER) were measured at predetermined times throughout the 23 week study period. Longitudinal analysis of AER indicated that diabetic B2R?/?D null mice had a significantly decreased AER levels compared to wild type B2R+/+D mice (P?=?0.0005). Results from the global microarray study comparing gene expression profiles among four groups of mice respectively: (B2R+/+C, B2R+/+D, B2R?/?C and B2R?/?D) highlighted the role of several altered pathological pathways in response to disruption of B2R and to the diabetic state that included: endothelial injury, oxidative stress, insulin and lipid metabolism and inflammatory process with a marked alteration in the pro-apoptotic genes. The findings of the present study provide a global genomics view of biomarkers that highlight the mechanisms and putative pathways involved in DN. PMID:23028588

Jaffa, Miran A.; Kobeissy, Firas; Al Hariri, Moustafa; Chalhoub, Hussein; Eid, Assaad; Ziyadeh, Fuad N.; Jaffa, Ayad A.

2012-01-01

208

Transplantation of cryopreserved human pancreatic islets into diabetic nude mice  

Microsoft Academic Search

If pancreatic islet transplantation becomes clinically applicable, cryogenic storage of human islet preparations could solve many problems related to transportation and banking of islets, HLA matching, recipient pretreatment, or the possible use of multiple donors. The diabetic nude mouse could offer a simple model to test in vivo the function of cryopreserved human islet preparations before transplantation into diabetic patients.

Camillo Ricordi; Norman M. Kneteman; David W. Scharp; Paul E. Lacy

1988-01-01

209

Genetic analysis of autoimmune type 1 diabetes mellitus in mice  

Microsoft Academic Search

Two genes, ldd-3 and ldd-4, that influence the onset of autoimmune type 1 diabetes in the nonobese diabetic mouse have been located on chromosomes 3 and 11, outside the chromosome 17 major histocompatibility complex. A genetic map of the mouse genome, analysed using the polymerase chain reaction, has been assembled specifically for the study. On the basis of comparative maps

John A. Todd; Timothy J. Aitman; Richard J. Cornall; Soumitra Ghosh; Jennifer R. S. Hall; Catherine M. Hearne; Andrew M. Knight; Jennifer M. Love; Marcia A. McAleer; Jan-Bas Prins; Nanda Rodrigues; Mark Lathrop; Alison Pressey; Nicole H. Delarato; Laurence B. Peterson; Linda S. Wicker

1991-01-01

210

Nitropravastatin stimulates reparative neovascularisation and improves recovery from limb Ischaemia in type-1 diabetic mice  

PubMed Central

Background and purpose: Mature endothelial cells and their progenitors are dysfunctional in diabetes, resulting in deficient neovascularisation following arterial occlusion. This study aimed to evaluate the therapeutic activity of a nitric oxide (NO) releasing statin in the setting of experimental diabetes and peripheral ischaemia. Experimental approach: The effects of NCX 6550, an NO-releasing pravastatin derivative, on angiogenesis in ischaemic limbs was studied in normoglycaemic mice or mice made diabetic by treatment with streptozotocin (STZ). Control mice received an equimolar dosage of the parent statin compound, pravastatin. The therapeutic action of NCX 6550 was also tested in mice lacking the gene for endothelial nitric oxide synthase (eNOS). Key Results: In normoglycaemic or STZ-diabetic CD1 mice, only NCX 6550 stimulated skeletal muscle revascularisation. In addition, NCX 6550 induced greater improvement in limb reperfusion and salvage, than pravastatin. The number of circulating endothelial progenitor cells was decreased in STZ-diabetic mice, this defect being prevented by NCX 6550 and, to a lesser extent by pravastatin. In vitro, high glucose concentrations reduced the migratory capacity of endothelial progenitor EPCs, which was partly reversed by preincubation with pravastatin and completely reversed by NCX 6550. The postischaemic recovery of eNOS knockout mice was severely impaired as a consequence of depressed angiogenesis and this recovery was improved by treatment with NCX 6550, but not with pravastatin. Conclusions and implications: These findings indicate that incorporation of a bioactive NO moiety improves the therapeutic profile of statins for the treatment of peripheral vascular disease. PMID:17351667

Emanueli, C; Monopoli, A; Kraenkel, N; Meloni, M; Gadau, S; Campesi, I; Ongini, E; Madeddu, P

2007-01-01

211

Reduction of blood glucose level by orexins in fasting normal and streptozotocin-diabetic mice.  

PubMed

Orexin-A and orexin-B are neuropeptides implicated in the maintenance of energy homeostasis. In the present study, we examined the effects of orexins on blood glucose levels in response to fasting in normal and streptozotocin-induced diabetic mice. After the injection of orexin-A and orexin-B (0.01-1 nmol/kg, i.v.), the blood glucose levels in both normal mice and diabetic mice in the fasting state decreased. In contrast, neither orexin-A nor orexin-B affected the glucose levels in the animals allowed free access to food. Intracerebroventricular administration of orexin-A and orexin-B was associated with glucose-lowering effects in fasting diabetic mice. The serum insulin level did not significantly change following the administration of orexin-A or orexin-B, in either the normal or the diabetic mice in the fasting state. These results demonstrate that orexins lower the blood glucose levels exclusively in the fasting state. The orexins may stimulate some neural and hormonal network and thereby promote blood glucose utilization. PMID:12144948

Tsuneki, Hiroshi; Sugihara, Yoshitaka; Honda, Ritsu; Wada, Tsutomu; Sasaoka, Toshiyasu; Kimura, Ikuko

2002-07-19

212

Proteomic Profile in Glomeruli of Type-2 Diabetic KKAy Mice using 2-Dimensional Differential Gel Electrophoresis  

PubMed Central

Background Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. To search for glomerular proteins associated with early-stage DN, glomeruli of spontaneous type 2 diabetic KKAy mice were analyzed by 2-dimensional differential gel electrophoresis (2D-DIGE). Material/Methods Glomeruli of 20-week spontaneous type 2 diabetic KKAy mice and age-matched C57BL/6 mice were isolated by kidney perfusion with magnetic beads. Proteomic profiles of glomeruli were investigated by using 2D-DIGE and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Western blot analysis was used to confirm the results of proteomics. Immunohistochemical and semi-quantitative analysis were used to confirm the differential expression of prohibitin and annexin A2 in glomeruli. Results We identified 19 differentially expressed proteins – 17 proteins were significantly up-regulated and 2 proteins were significantly down-regulated in glomeruli of diabetic KKAy mice. Among them, prohibitin and annexin A2 were up-regulated and Western blot analysis validated the same result in proteomics. Immunohistochemical analysis also revealed up-regulation of prohibitin and annexin A2 in glomeruli of KKAy mice. Conclusions Our findings suggest that prohibitin and annexin A2 may be associated with early-stage DN. Further functional research might help to reveal the pathogenesis of DN. PMID:25515740

Liu, Xiaodan; Yang, Gang; Fan, Qiuling; Wang, Lining

2014-01-01

213

Effects of diabetes on rabbit kidney and lung CYP2E1 and CYP2B4 expression and drug metabolism and potentiation of carcinogenic activity of N-nitrosodimethylamine in kidney and lung.  

PubMed

There are limited number of studies regarding the influence of diabetes on the regulation of cytochrome P450s and associated drug metabolizing enzyme activities especially in extrahepatic tissues such as kidney. However, there is almost no such study in lung. Alloxan-induced diabetes did not change CYP2B4 expression as measured with immunoblot analysis and associated enzyme, benzphetamine N-demethylase, activity in rabbit kidney and lung. Induction of cytochrome P4502E1 by diabetes was identified by immunochemical detection on Western blots in the lung and kidney microsomes of rabbits. In parallel to CYP2E1 induction, aniline 4-hydroxylase and p-nitrophenol hydroxylase activities were markedly increased in diabetic rabbit lung and kidney. CYP2B4 and CYP2E1 dependent drug metabolism did not show any tissue variation in diabetic rabbit. These findings are in contrast to those of rats, mice and hamster. The results of the present work, in combination with those of the previous work [Arinç, E., Arslan, S., Adali, O., 2005. Differential effects of diabetes on CYP2E1 and CYP2B4 proteins and associated drug metabolizing enzyme activities in rabbit liver. Arch. Toxicol. 79, 427-433], indicate the existence of species-dependent response of CYP-dependent drug metabolizing enzymes to diabetes. A procarcinogen and food contaminant, N-nitrosodimethylamine (NDMA), is converted to its carcinogenic form after it is activated with NDMA N-demethylase. In the current study, a statistically significant increase of liver, kidney and lung NDMA N-demethylase activity associated with CYP2E1 was shown in diabetic rabbit. Thus, it is expected that, the risk of nitrosamine induced carcinogenesis will be greater in liver, kidney and lung of the diabetic subjects. PMID:17034923

Arinç, Emel; Arslan, Sevki; Bozcaarmutlu, Azra; Adali, Orhan

2007-01-01

214

Unconjugated bilirubin mediates heme oxygenase-1-induced vascular benefits in diabetic mice.  

PubMed

Heme oxygenase-1 (HO-1) exerts vaso-protective effects. Such benefit in diabetic vasculopathy however remains unclear. We hypothesize that bilirubin mediates HO-1-induced vascular benefits in diabetes. Diabetic db/db mice were treated with hemin (HO-1 inducer) for two weeks, and aortas were isolated for functional and molecular assays. Nitric oxide (NO) production was measured in cultured endothelial cells. Hemin treatment augmented endothelium-dependent relaxations (EDRs) and elevated Akt and eNOS phosphorylation in db/db mouse aortas, which were reversed by HO-1 inhibitor SnMP or HO-1 silencing virus. Hemin treatment increased serum bilirubin and ex vivo bilirubin treatment improved relaxations in diabetic mouse aortas, which was reversed by Akt inhibitor. Biliverdin reductase silencing virus attenuated the effect of hemin. Chronic bilirubin treatment improved EDRs in db/db mouse aortas. High glucose-induced reductions in Akt and eNOS phosphorylation, and NO production were reversed by hemin and bilirubin. The effect of hemin but not bilirubin was inhibited by biliverdin reductase shRNA. Furthermore, bilirubin augmented EDRs in renal arteries from diabetic patients. In summary, HO-1-induced restoration of endothelial function in diabetic mice is most likely mediated by bilirubin which preserves NO bioavailability through the Akt/eNOS/NO cascade, suggesting bilirubin as a potential therapeutic target for clinical intervention of diabetic vasculopathy. PMID:25475440

Liu, Jian; Wang, Li; Tian, Xiaoyu; Liu, Limei; Wong, Wing-Tak; Zhang, Yang; Han, Quanbin; Ho, Hing-Man; Wang, Nanping; Wong, Siu-Ling; Chen, Zhenyu; Yu, Jun; Ng, Chi-Fai; Yao, Xiaoqiang; Huang, Yu

2014-12-01

215

Edaravone Protect against Retinal Damage in Streptozotocin-Induced Diabetic Mice  

PubMed Central

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, is used for the clinical treatment of retinal injury. In this study, we investigated the protective effects of edaravone against diabetic retinal damage in the mouse. Diabetic retinopathy in the mouse was induced by injection of streptozotocin. Edaravone was given once-daily and was intraperitoneally (i.p.) treated at a dose of 3 mg/kg from streptozotocin injection to 4 weeks after onset of diabetes. Retinal ganglion cells (RGCs) damage was evaluated by recording the pattern electroretinogram (ERG). RGCs damage was also detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the levels of reactive oxygen species (ROS) were determined fluorometrically. The expressions of phosporylated-ERK1/2, BDNF, and caspase-3 were determined by Western blot analysis. Retinal levels of ROS, phosphorylated ERK1/2, and cleaved caspase-3 were significantly increased, whereas the expression of BDNF was significantly decreased in the retinas of diabetic mice, compared to nondiabetic mice. Administration of edaravone significantly attenuated diabetes induced RGCs death, upregulation of ROS, ERK1/2 phosphorylation, and cleaved caspase-3 and downregulation of BDNF. These findings suggest that oxidative stress plays a pivotal role in diabetic retinal damage and that systemic administration of edaravone may slow the progression of retinal neuropathy induced by diabetes. PMID:24897298

Liu, Xiaoyi; Chen, Xi; Xie, Ping; Yuan, Songtao; Zhang, Weiwei; Lin, Xiaojun; Liu, Qinghuai

2014-01-01

216

Edaravone protect against retinal damage in streptozotocin-induced diabetic mice.  

PubMed

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, is used for the clinical treatment of retinal injury. In this study, we investigated the protective effects of edaravone against diabetic retinal damage in the mouse. Diabetic retinopathy in the mouse was induced by injection of streptozotocin. Edaravone was given once-daily and was intraperitoneally (i.p.) treated at a dose of 3 mg/kg from streptozotocin injection to 4 weeks after onset of diabetes. Retinal ganglion cells (RGCs) damage was evaluated by recording the pattern electroretinogram (ERG). RGCs damage was also detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the levels of reactive oxygen species (ROS) were determined fluorometrically. The expressions of phosporylated-ERK1/2, BDNF, and caspase-3 were determined by Western blot analysis. Retinal levels of ROS, phosphorylated ERK1/2, and cleaved caspase-3 were significantly increased, whereas the expression of BDNF was significantly decreased in the retinas of diabetic mice, compared to nondiabetic mice. Administration of edaravone significantly attenuated diabetes induced RGCs death, upregulation of ROS, ERK1/2 phosphorylation, and cleaved caspase-3 and downregulation of BDNF. These findings suggest that oxidative stress plays a pivotal role in diabetic retinal damage and that systemic administration of edaravone may slow the progression of retinal neuropathy induced by diabetes. PMID:24897298

Yuan, Dongqing; Xu, Yidan; Hang, Hui; Liu, Xiaoyi; Chen, Xi; Xie, Ping; Yuan, Songtao; Zhang, Weiwei; Lin, Xiaojun; Liu, Qinghuai

2014-01-01

217

Antioxidative Action of Corni Fructus Aqueous Extract on Kidneys of Diabetic Mice  

PubMed Central

This study investigated the antioxidative action of Corni Fructus aqueous extract on kidneys of diabetic mice. The electron donating abilities of Corni Fructus aqueous extract and its antioxidant activities (XO, SOD, CAT, GST, eNOS) in kidneys of C57BL/6 or db/db mice were evaluated. For in vivo study, seven week-old male mice were divided into normal control group (NC, C57BL/6 mice) , diabetic control group (DC, db/db mice) and Corni Fructus (500 mg/kg/day for 8 weeks) treated diabetic group (DCF, db/db mice) . The electron donating abilities of Corni Fructus aqueous extract exhibited 7%, 24.4%, and 42.7% at concentrations of 100, 500, and 1000 ?g/ml, respectively. The activity of XO in the DCF group was significantly lower than the DC group by 35% (p < 0.05) . The SOD activity was significantly higher in the DCF group than the DC group by 26% (p < 0.05) . The activities of CAT and GST were lowered in the DCF group than the DC group by 26% (p < 0.05) and 7.6%, respectively. The mRNA expression of eNOS in kidneys was lower in the DCF group than the DC group by 24%. These results indicate that Corni Fructus reduced oxidation stress as evidenced by the restoration of the enzymatic antioxidative defense system in renal tissues of db/db mice. It is suggested that these antioxidative actions of Corni Fructus on renal tissues in db/db mice could contribute to its renoprotective effects on diabetic nephropathy. PMID:24278549

Kim, Hye-Jeong; Kim, Bae-Hwan; Kim, Young-Chul

2011-01-01

218

Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment  

PubMed Central

Background While all anti-diabetic agents can decrease blood glucose level directly or indirectly, few are able to protect and preserve both pancreatic beta cell mass and their insulin-secreting functions. Thus, there is an urgent need to find an agent or combination of agents that can lower blood glucose and preserve pancreatic beta cells at the same time. Herein, we report a dual-functional andrographolide-lipoic acid conjugate (AL-1). The anti-diabetic and beta cell protective activities of this novel andrographolide-lipoic acid conjugate were investigated. Methods In alloxan-treated mice (a model of type 1 diabetes), drugs were administered orally once daily for 6 days post-alloxan treatment. Fasting blood glucose and serum insulin were determined. Pathologic and immunohistochemical analysis of pancreatic islets were performed. Translocation of glucose transporter subtype 4 in soleus muscle was detected by western blot. In RIN-m cells in vitro, the effect of AL-1 on H2O2-induced damage and reactive oxidative species production stimulated by high glucose and glibenclamide were measured. Inhibition of nuclear factor kappa B (NF-?B) activation induced by IL-1? and IFN-? was investigated. Results In alloxan-induced diabetic mouse model, AL-1 lowered blood glucose, increased insulin and prevented loss of beta cells and their dysfunction, stimulated glucose transport protein subtype 4 (GLUT4) membrane translocation in soleus muscles. Pretreatment of RIN-m cells with AL-1 prevented H2O2-induced cellular damage, quenched glucose and glibenclamide-stimulated reactive oxidative species production, and inhibited cytokine-stimulated NF-?B activation. Conclusion We have demonstrated that AL-1 had both hypoglycemic and beta cell protective effects which translated into antioxidant and NF-?B inhibitory activity. AL-1 is a potential new anti-diabetic agent. PMID:19607676

2009-01-01

219

Antidiabetic efficacy of bradykinin antagonist R-954 on glucose tolerance test in diabetic type 1 mice.  

PubMed

Insulin-dependent diabetes mellitus (type 1 diabetes) is an inflammatory autoimmune disease associated with many complications including nephropathy, retinopathy, neuropathy and hyperalgesia. Experimental evidence has shown that the bradykinin B1 receptor (BKB1-R) is involved in the development of type 1 diabetes and found to be upregulated alongside the disease. In the present study the effects of the selective BKB1-R antagonist the R-954 (Ac-Orn-[Oic(2), alpha-MePhe(5), D-beta Nal(7), Ile(8) ]des-Arg(9)-BK and the BKB1-R agonist des Arg(9)-BK (DBK) were studied on diabetic hyperglycemia. Diabetic type 1 was induced in C57 BL/KsJ mdb male mice by five consecutives doses of STZ (45mg/kg i.p.). A glucose tolerance test (GTT) was performed by an intraperitoneal administration of glucose, 8, 12 and 18days after the diabetes induction. The induction of type 1 diabetes provoked a significant hyperglycemia levels in diabetic mice at 12 and 18days after STZ. The administration of R-954 (400microg/kg i.p.) at 12 and 18days after STZ returned the glycemia levels of this animals to normal values. In addition the administration of DKB (300microg/kg i.p.) significantly potentiated the diabetes-induced hyperglycemia; this effect that was totally reversed by R-954. These results provide further evidence for the implication of BKB1-R in the type 1 diabetes mellitus (insulitis). PMID:20092893

Catanzaro, Orlando L; Dziubecki, Damian; Obregon, Pablo; Rodriguez, Ricardo R; Sirois, Pierre

2010-04-01

220

Development of Type 1 Diabetes Mellitus in Nonobese Diabetic Mice Follows Changes in Thymocyte and Peripheral T Lymphocyte Transcriptional Activity  

PubMed Central

As early as one month of age, nonobese diabetic (NOD) mice feature pancreatic infiltration of autoreactive T lymphocytes, which destruct insulin-producing beta cells, producing autoimmune diabetes mellitus (T1D) within eight months. Thus, we hypothesized that during the development of T1D, the transcriptional modulation of immune reactivity genes may occur as thymocytes mature into peripheral T lymphocytes. The transcriptome of thymocytes and peripheral CD3+ T lymphocytes from prediabetic or diabetic mice analyzed through microarray hybridizations identified 2,771 differentially expressed genes. Hierarchical clustering grouped mice according to age/T1D onset and genes according to their transcription profiling. The transcriptional activity of thymocytes developing into peripheral T lymphocytes revealed sequential participation of genes involved with CD4+/CD8+ T-cell differentiation (Themis), tolerance induction by Tregs (Foxp3), and apoptosis (Fasl) soon after T-cell activation (IL4), while the emergence of T1D coincided with the expression of cytotoxicity (Crtam) and inflammatory response genes (Tlr) by peripheral T lymphocytes. PMID:21765850

Fornari, Thais A.; Donate, Paula B.; Macedo, Claudia; Sakamoto-Hojo, Elza T.; Donadi, Eduardo A.; Passos, Geraldo A.

2011-01-01

221

Effect of whey protein on plasma amino acids in diabetic mice  

PubMed Central

The aim of this study was to investigate the effect of whey protein on plasma amino acid levels in a mouse model of type II diabetes, using high-performance liquid chromatography (HPLC). The composition and content of amino acids in the whey proteins were analyzed using HPLC. Type I and type II diabetic mouse models were prepared using streptozotocin (STZ) and normal mice were used as a control. The ICR mice in each group were then randomly divided into four subgroups, to which 0, 10, 20 and 40% whey protein, respectively, was administered for four weeks. Changes in the plasma amino acid levels were observed in each group. The proportions of leucine, isoleucine and valine in the whey proteins were 14.40, 5.93 and 5.32% of the total amino acids, respectively, that is, the branched-chain amino acid content was 25.65%. The levels of branched-chain amino acids increased in the plasma of the normal and model mice following the administration of whey proteins by gavage and the amino acid levels increased as the concentration of the administered protein increased. In addition, the branched-chain amino acid levels in the blood of the model mice were higher than those in the normal mice. The levels of plasma amino acids in diabetic mice increased following gavage with whey protein, which is rich in branched-chain amino acids. PMID:24255674

HAN, TING; CAI, DONGLIAN; GENG, SHANSHAN; WANG, YING; ZHEN, HUI; WU, PEIYING

2013-01-01

222

Long-Term Low Carbohydrate Diet Leads to Deleterious Metabolic Manifestations in Diabetic Mice  

PubMed Central

We investigated long-term effects of low carbohydrate diets on wild type mice, streptozotocin-injected and KKAy obese diabetic mice. These mice were pair-fed three different types of diets, standard chow (SC, C?P?F?=?63?15?22), a low carbohydrate (LC, C?P?F?=?38?25?37) diet and a severely carbohydrate restricted (SR, C?P?F?=?18?45?37) diet for 16 weeks. Despite comparable body weights and serum lipid profiles, wild type and diabetic mice fed the low carbohydrate diets exhibited lower insulin sensitivity and this reduction was dependent on the amount of carbohydrate in the diet. When serum fatty acid compositions were investigated, monounsaturation capacity, i.e. C16:1/C16:0 and C18:1/C18:0, was impaired in all murine models fed the low carbohydrate diets, consistent with the decreased expression of hepatic stearoyl-CoA desaturase-1 (SCD1). Interestingly, both the hepatic expressions and serum levels of fibroblast growth factor 21 (FGF21), which might be related to longevity, were markedly decreased in both wild type and KKAy mice fed the SR diet. Taking into consideration that fat compositions did not differ between the LC and SR diets, we conclude that low carbohydrate diets have deleterious metabolic effects in both wild type and diabetic mice, which may explain the association between diets relatively low in carbohydrate and the elevated risk of cardiovascular events observed in clinical studies. PMID:25170869

Handa, Keiko; Inukai, Kouichi; Onuma, Hirohisa; Kudo, Akihiko; Nakagawa, Fumiyuki; Tsugawa, Kazue; Kitahara, Atsuko; Moriya, Rie; Takahashi, Kazuto; Sumitani, Yoshikazu; Hosaka, Toshio; Kawakami, Hayato; Oyadomari, Seiichi; Ishida, Hitoshi

2014-01-01

223

Ursolic Acid Protects Diabetic Mice Against Monocyte Dysfunction and Accelerated Atherosclerosis  

PubMed Central

Aims Accelerated atherosclerosis is a major diabetic complication initiated by the enhanced recruitment of monocytes into the vasculature. In this study, we examined the therapeutic potential of the phytonutrients ursolic acid (UA) and resveratrol (RES) in preventing monocyte recruitment and accelerated atherosclerosis. Methods and Results Dietary supplementation with either RES or UA (0.2%) protected against accelerated atherosclerosis induced by streptozotocin in high-fat diet-fed LDL receptor-deficient mice. However, mice that received dietary UA for 11 weeks were significantly better protected and showed a 53% reduction in lesion formation while mice fed a RES-supplemented diet showed only a 31% reduction in lesion size. Importantly, UA was also significantly more effective in preventing the appearance of proinflammatory GR-1high monocytes induced by these diabetic conditions and reducing monocyte recruitment into MCP-1-loaded Matrigel plugs implanted into these diabetic mice. Oxidatively-stressed THP-1 monocytes mimicked the behavior of blood monocytes in diabetic mice and showed enhanced responsiveness to monocyte chemoattractant protein-1 (MCP-1) without changing MCP-1 receptor (CCR2) surface expression. Pretreatment of THP-1 monocytes with RES or UA (0.3 – 10 ?M) for 15 h resulted in the dose-dependent inhibition of H2O2-accelerated chemotaxis in response to MCP-1, but with an IC50 of 0.4 ?M, UA was 2.7-fold more potent than RES. Conclusion Dietary UA is a potent inhibitor of monocyte dysfunction and accelerated atherosclerosis induced by diabetes. These studies identify ursolic acid as a potential therapeutic agent for the treatment of diabetic complications, including accelerated atherosclerosis, and provide a novel mechanism for the anti-atherogenic properties of ursolic acid. PMID:21752377

Ullevig, Sarah L.; Zhao, Qingwei; Zamora, Debora; Asmis, Reto

2011-01-01

224

Caprine pancreatic islet xenotransplantation into diabetic immunosuppressed BALB/c mice  

PubMed Central

Background Type 1 diabetes mellitus is a devastating disease for which there is currently no cure, but only lifetime management. Islet xenotransplantation is a promising technique for the restoration of blood glucose control in patients with diabetes mellitus. The purpose of this study was to explore the potential use of caprine (goat) islet cells as xenogeneic grafts in the treatment for diabetes in a mouse model. Methods Caprine pancreases were harvested and transported to the laboratory under conditions optimized to prevent ischemia. Islets were isolated, purified, and tested for functionality. Caprine islets (2000 islet equivalent) were transplanted beneath the kidney capsules of diabetic BALB/c mice under thalidomide-induced immunosuppression. Blood glucose and insulin levels of grafted mice were evaluated by glucometer and enzyme-linked immunosorbent assay kit, respectively. The functionality and quality of caprine pancreatic islet grafts were assessed by intraperitoneal glucose tolerance tests. Results The viability of purified islet cells exceeded 90%. Recipient mice exhibited normoglycemia (<11 mm glucose) for 30 days. In addition, weight gain negatively correlated with blood glucose level. The findings verified diabetes reversal in caprine islet recipient mice. A significant drop in non-fasting blood glucose level (from 23.3 ± 5.4 to 8.04 ± 0.44 mm) and simultaneous increase in serum insulin level (from 0.01 ± 0.001 to 0.56 ± 0.17 ?g/l) and body weights (from 23.64 ± 0.31 to 25.85 ± 0.34 g) were observed (P < 0.05). Immunohistochemical analysis verified insulin production in the transplanted islets. Conclusions Purified caprine islets were demonstrated to successfully sustain viability and functionality for controlling blood glucose levels in an immunosuppressed mouse model of diabetes. These results suggest the use of caprine islets as an addition to the supply of xenogeneic islets for diabetes research. PMID:24645790

Hani, Homayoun; Allaudin, Zeenathul N; Mohd-Lila, Mohd-Azmi; Ibrahim, Tengku A Tengku; Othman, Abas M

2014-01-01

225

Proanthocyanidin Attenuation of Oxidative Stress and NF-?B Protects Apolipoprotein E-Deficient Mice against Diabetic Nephropathy  

PubMed Central

Hyperlipidemia and hyperglycemia result in oxidative stress and play a major role in the development of diabetic nephropathy (DN). We explored the effects of proanthocyanidin (PA) on the induction and progression of DN in apolipoprotein E-deficient mice. Diabetes Mellitus was induced in ten-week-old male apoE?/?mice using streptozotocin (STZ). Mice were fed with a high-fat diet in presence or absence of PA. PA treatment significantly reduced the high cholesterol levels, restored renal functions, and reduced albuminuria in the PA-treated diabetic mice compared with the diabetic untreated mice. In addition, the glomerular mesangial expansion in the diabetic mice was attenuated as a result of PA supplementation. Moreover, PA treatment restored the elevated levels of MDA and CML and the reduced activity of SOD and GSH in the diabetic mice. Furthermore, PA feeding reduced the activation and translocation of NF-?B to the nucleus compared with the diabetic untreated animals. Reduction of NF-?B activation resulted in the attenuation of the expression of IL-6, TGF?, and RAGE which protected PA-treated mice against DN. The renoprotective effects of PA were found to be time independent regardless of whether the dietary feeding with PA was started pre-, co-, or post-STZ injection. In conclusion, part of the beneficial effects of PA includes the disruption of the detrimental AGE-RAGE-NF?B pathways. PMID:24023581

Al-Malki, Abdulrahman L.; Sayed, Ahmed Amir Radwan; El Rabey, Haddad A.

2013-01-01

226

Synaptic transmission at parasympathetic neurons of the major pelvic ganglion from normal and diabetic male mice  

PubMed Central

Bladder and erectile dysfunction are common urologic complications of diabetes and are associated with reduced parasympathetic autonomic control. To determine whether disruption of ganglionic neurotransmission contributes to the loss of function, we investigated synaptic transmission at parasympathetic, major pelvic ganglion (MPG) neurons in control and chronically (20 wk) diabetic mice. In contrast to what has been reported for sympathetic neurons, diabetes did not cause an interruption of synaptic transmission at parasympathetic MPG neurons from streptozotocin-treated C57BL/6J (STZ) or db/db mice. Cholinergically mediated excitatory postsynaptic potentials (EPSPs) were suprathreshold during 5-s trains of 5-, 10-, and 20-Hz stimuli. Asynchronous neurotransmitter release, observed as miniature EPSPs (mEPSPs) during and after stimulation, permitted quantitative assessment of postganglionic, cholinergic receptor sensitivity. mEPSP amplitude following tetanic stimulation (recorded at ?60 mV) was reduced in STZ (4.95 ± 0.4 vs. 3.71 ± 0.3 mV, P = 0.03), but not db/db mice. The number of posttetanic mEPSPs was significantly greater in db/db mice at all frequencies tested. Assessment of basic electrophysiological properties revealed that parasympathetic MPG neurons from db/db mice had less negative membrane potentials, lower input resistances, and shorter afterhyperpolarizations relative to their control. MPG neurons from STZ had longer afterhyperpolarizations but were otherwise similar to controls. Membrane excitability, measured by the membrane responsiveness to long-duration (1 s), suprathreshold depolarizing pulses, was unchanged in either model. The present study indicates that, while parasympathetic neurotransmission at the MPG is intact in chronically diabetic mice, obese, type 2 diabetic animals exhibit an altered presynaptic regulation of neurotransmitter release. PMID:23197460

Vizzard, Margaret A.; Parsons, Rodney L.

2013-01-01

227

Abnormal splicing of the leptin receptor in diabetic mice  

Microsoft Academic Search

MUTATIONS in the mouse diabetes(db) gene result in obesity and diabetes in a syndrome resembling morbid human obesity1. Previous data suggest that the db gene encodes the receptor for the obese(ob) gene product, leptin2-7. A leptin receptor was recently cloned from choroid plexus and shown to map to the same 6-cM interval on mouse chromosome 4 as db8. This receptor

Gwo-Hwa Lee; R. Proenca; J. M. Montez; K. M. Carroll; J. G. Darvishzadeh; J. I. Lee; J. M. Friedman

1996-01-01

228

Deconstructing and reconstructing obesity-induced diabetes (diabesity) in mice  

Microsoft Academic Search

Obesity-driven type 2 diabetes (diabesity) involves complex genetic and environmental interactions to trigger disease. Here, we combine variable numbers of known quantitative trait loci (QTL) for obesity and diabetes contributed by New Zealand Obese (NZO\\/HlLt) and Nonobese Nondiabetic (NON\\/Lt) strains in the form of 10 interval-directed recombinant congenic strains (RCS), with NON\\/Lt as the background strain, to dissect the genetic

P. C. Reifsnyder; E. H. Leiter

2002-01-01

229

Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice  

PubMed Central

Background Caffeic acid (CA) and ellagic acid (EA) are phenolic acids naturally occurring in many plant foods. Cardiac protective effects of these compounds against dyslipidemia, hypercoagulability, oxidative stress and inflammation in diabetic mice were examined. Methods Diabetic mice were divided into three groups (15 mice per group): diabetic mice with normal diet, 2% CA treatment, or 2% EA treatment. One group of non-diabetic mice with normal diet was used for comparison. After 12 weeks supplement, mice were sacrificed, and the variation of biomarkers for hypercoagulability, oxidative stress and inflammation in cardiac tissue of diabetic mice were measured. Results The intake of CA or EA significantly increased cardiac content of these compounds, alleviated body weight loss, elevated plasma insulin and decreased plasma glucose levels in diabetic mice (p < 0.05). These treatments also significantly enhanced plasma antithrombin-III and protein C activities (p < 0.05); and decreased triglyceride content in cardiac tissue and plasma (p < 0.05), in which the hypolipidemic effects of EA were significantly greater than that of CA (p < 0.05). CA or EA significantly lowered cardiac levels of malondialdehyde, reactive oxygen species, interleukin (IL)-beta, IL-6, tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1 (p < 0.05); and retained cardiac activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (p < 0.05). These compounds also significantly up-regulated cardiac mRNA expression of GPX1, SOD and catalase; and down-regulated IL-1beta, IL-6, TNF-alpha and MCP-1 mRNA expression in diabetic mice (p < 0.05). Conclusion These results support that CA and EA could provide triglyceride-lowering, anti-coagulatory, anti-oxidative, and anti-inflammatory protection in cardiac tissue of diabetic mice. Thus, the supplement of these agents might be helpful for the prevention or attenuation of diabetic cardiomyopathy. PMID:19678956

Chao, Pei-chun; Hsu, Cheng-chin; Yin, Mei-chin

2009-01-01

230

Gene expression microarray analysis of the sciatic nerve of mice with diabetic neuropathy.  

PubMed

The present study aimed to explore novel target genes that regulate the development of diabetic neuropathy (DN) by analyzing gene expression profiles in the sciatic nerve of infected mice. The GSE11343 microarray dataset, which was downloaded from Gene Expression Omnibus, included data on 4 control samples and 5 samples from mice with diabetes induced by streptozotocin (STZ), 5 samples from normal mice treated with rosiglitazone (Rosi) and 5 samples from mice with diabetes induced by STZ and treated with Rosi. Differentially expressed genes (DEGs) between the different groups were identified using the substitution augmentation modification redefinition (SAMR) model. The Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Regulatory and protein?protein interaction networks were searched using BioCarta and STRING, respectively. The protein structures of potential regulatory genes were predicted using the SYBYL program. Compared with the controls, 1,384 DEGs were identified in the mice with STZ-induced diabetes and 7 DEGs were identified in the mice treated with Rosi. There were 518 DEGs identified between the mice in the STZ + Rosi and STZ groups. We identified 45 GO items, and the calmodulin nerve phosphatase and chemokine signaling pathways were identified as the main pathways. Three genes [myristoylated alanine-rich protein kinase C substrate (Marcks), GLI pathogenesis-related 2 (Glipr2) and centrosomal protein 170 kDa (Cep170)] were found to be co-regulated by both STZ and Rosi, the protein structure of which was predicted and certain binding activity to Rosi was docked. Our study demonstrates that the Marcks, Glipr2 and Cep170 genes may be underlying drug targets in the treatment of DN. PMID:25435094

Zhang, Lei; Qu, Shen; Liang, Aibin; Jiang, Hong; Wang, Hao

2015-02-01

231

Impaired adiponectin signaling contributes to disturbed catabolism of branched-chain amino acids in diabetic mice.  

PubMed

The branched-chain amino acids (BCAA) accumulated in type 2 diabetes are independent contributors to insulin resistance. The activity of branched-chain ?-keto acid dehydrogenase (BCKD) complex, rate-limiting enzyme in BCAA catabolism, is reduced in diabetic states, which contributes to elevated BCAA concentrations. However, the mechanisms underlying decreased BCKD activity remain poorly understood. Here, we demonstrate that mitochondrial phosphatase 2C (PP2Cm), a newly identified BCKD phosphatase that increases BCKD activity, was significantly downregulated in ob/ob and type 2 diabetic mice. Interestingly, in adiponectin (APN) knockout (APN(-/-)) mice fed with a high-fat diet (HD), PP2Cm expression and BCKD activity were significantly decreased, whereas BCKD kinase (BDK), which inhibits BCKD activity, was markedly increased. Concurrently, plasma BCAA and branched-chain ?-keto acids (BCKA) were significantly elevated. APN treatment markedly reverted PP2Cm, BDK, BCKD activity, and BCAA and BCKA levels in HD-fed APN(-/-) and diabetic animals. Additionally, increased BCKD activity caused by APN administration was partially but significantly inhibited in PP2Cm knockout mice. Finally, APN-mediated upregulation of PP2Cm expression and BCKD activity were abolished when AMPK was inhibited. Collectively, we have provided the first direct evidence that APN is a novel regulator of PP2Cm and systematic BCAA levels, suggesting that targeting APN may be a pharmacological approach to ameliorating BCAA catabolism in the diabetic state. PMID:25071024

Lian, Kun; Du, Chaosheng; Liu, Yi; Zhu, Di; Yan, Wenjun; Zhang, Haifeng; Hong, Zhibo; Liu, Peilin; Zhang, Lijian; Pei, Haifeng; Zhang, Jinglong; Gao, Chao; Xin, Chao; Cheng, Hexiang; Xiong, Lize; Tao, Ling

2015-01-01

232

INFLUENCE OF TYPE II DIABETES AND OBESITY ON THE DISPOSITION AND ELIMINATION OF TCDD IN MICE  

EPA Science Inventory

INFLUENCE OF TYPE II DIABETES AND OBESITY ON THE DISPOSTION AND ELIMINATION OF TCDD IN MICE. MJ DeVito', JJ Diliberto', DG Ross', C Emond2, VM Richardson', and LS Birnbaum', 'ETD, NHEERL, ORD, US EPA, RTP, NC, 27711, USA, 2National Research Council. One possible explanation fo...

233

Anti-diabetic activity of a leaf extract prepared from Salacia reticulata in mice.  

PubMed

The effects of a water extract prepared from the leaves of Salacia reticulata on the absorption of sugars in normal and type 1 diabetic mice were investigated. The simultaneous oral administration of the extract at a dose of 1.0 mg/mouse with maltose or sucrose inhibited the postprandial elevation of the plasma glucose and insulin levels and intestinal alpha-glucosidase activities in mice. In addition, the supply of a 0.01% solution of the extract as drinking water prevented the elevation of the plasma glucose level and intestinal alpha-glucosidase activities in type 1 diabetic mice. This treatment also prevented the elevation of the plasma, pancreatic, and kidney lipid peroxide levels, lowering of the plasma insulin level, and elevation of the kidney aldose reductase activities in diabetic mice. These results suggest that the water extract of the leaves of S. reticulata could be a beneficial food material for the prevention of diabetes and obesity because of its multiple effects. PMID:19420711

Yoshino, Kyoji; Miyauchi, Yuko; Kanetaka, Takashi; Takagi, Yasutaka; Koga, Kunimasa

2009-05-01

234

Intestinal Colonization by a Lachnospiraceae Bacterium Contributes to the Development of Diabetes in Obese Mice  

PubMed Central

The aim of the present study was to identify bacteria that may contribute to the onset of metabolic dysfunctions. We isolated and identified a candidate bacterium belonging to Lachnospiraceae (strain AJ110941) in the feces of hyperglycemic obese mice. The colonization of germ-free ob/ob mice by AJ110941 induced significant increases in fasting blood glucose levels as well as liver and mesenteric adipose tissue weights, and decreases in plasma insulin levels and HOMA-? values. These results indicated that the specific gut commensal bacterium AJ110941 influenced the development of obesity and diabetes in ob/ob mice with genetic susceptibility for obesity.

Kameyama, Keishi; Itoh, Kikuji

2014-01-01

235

Topical application of yeast extract accelerates the wound healing of diabetic mice.  

PubMed

Alcoholic extracts of yeast have been used as the active ingredient in medications under names such as "tissue or skin respiratory factor," Biodyne (Sperti Drug Co, Cincinnati, Ohio--now defunct), and live yeast cell derivative (LYCD). Beneficial clinical results from the use of LYCD have been reported for the treatment of burns, wounds, and hemorrhoids. The medicinal effects of LYCD have recently been localized to a protein fraction containing a mixture of several peptides. The effects of topical application of the peptide mixture on wounds were examined in diabetic mice, an animal model in which the healing process is disrupted and delayed. Full-thickness wounds were created on the backs of diabetic (DB) and nondiabetic (non-DB) mice. Half of the DB and non-DB mice were treated with 0.05 mL of LYCD after wounding and for 4 successive days. All other mice received vehicle. Wound areas were measured at Day 0 and at 2-day intervals. Mice were sacrificed at 3, 7, 10, 21, and 28 days postinjury. Differences in the extent and quality of healing appeared between DB mice receiving LYCD and DB mice receiving vehicle by day 10 (P < .0001). By 24 days postinjury, DB mice receiving LYCD had achieved 100% wound closure, whereas DB mice receiving vehicle had achieved only 31.4% wound closure. Histologic examination of wounds reflected improved wound healing in DB mice receiving LYCD as compared with those receiving vehicle. A topically applied yeast extract peptide mixture significantly attenuates wound closure and the degree of cellular reorganization of full-thickness excisional wounds of DB mice. PMID:10188114

Crowe, M J; McNeill, R B; Schlemm, D J; Greenhalgh, D G; Keller, S J

1999-01-01

236

Prevention of adoptively transferred diabetes in nonobese diabetic mice with IL-10-transduced islet-specific Th1 lymphocytes. A gene therapy model for autoimmune diabetes.  

PubMed Central

Four pancreatic islet-specific CD4+ helper T (Th) 1 (Th1) clones and two Th1 clones transduced with an SRalpha promoter-linked murine IL-10 (mIL-10) cDNA of 2.0-6.0 x 10(6) cells were adoptively transferred to nonobese diabetic (NOD) mice at age 8 d. Cyclophosphamide (CY) was administered at age 37 d (plus CY), and the incidence of diabetes and the histological grade of insulitis were examined at age 47 d. After the adoptive transfer of IL-10-transduced Th1 cells, polymerase chain reaction (PCR) and reverse-transcription (RT)-PCR detected the neo gene and the retrovirus vector-mediated IL-10 mRNA in situ in recipient islets, respectively. RT-PCR detected the decrease of IFN-gamma mRNA relative to IL-10 mRNA in IL-10-transduced Th1 clones in vitro and also in recipient islets. All four wild type Th1 clones plus CY induced the insulitis grade of 2.75 and diabetes in 66% of recipient NOD mice. IL-10-transduced two Th1 clones plus CY induced periinsulitis with the grade of 1.43 and diabetes in 8.0%. The 1:1 mixture of wild type Th1 cells and IL-10-transduced Th1 cells plus CY induced periinsulitis with the grade of 1.85 and diabetes in 20%. The suppression of diabetes through decreasing IFN-gamma mRNA by the tissue-specific delivery of IL-10 to pancreatic islets with IL-10-transduced Th1 cells affords us the starting basis to develop the gene therapy for autoimmune diabetes. PMID:8878437

Moritani, M; Yoshimoto, K; Ii, S; Kondo, M; Iwahana, H; Yamaoka, T; Sano, T; Nakano, N; Kikutani, H; Itakura, M

1996-01-01

237

Marrow-Derived Cells Regulate the Development of Early Diabetic Retinopathy and Tactile Allodynia in Mice  

PubMed Central

The hypothesis that marrow-derived cells, and specifically proinflammatory proteins in those cells, play a critical role in the development of diabetes-induced retinopathy and tactile allodynia was investigated. Abnormalities characteristic of the early stages of retinopathy and allodynia were measured in chimeric mice lacking inducible nitric oxide synthase (iNOS) or poly(ADP-ribosyl) polymerase (PARP1) in only their marrow-derived cells. Diabetes-induced capillary degeneration, proinflammatory changes, and superoxide production in the retina and allodynia were inhibited in diabetic animals in which iNOS or PARP1 was deleted from bone marrow cells only. Of the various marrow cells, neutrophils (and monocytes) play a major role in retinopathy development, because retinal capillary degeneration likewise was significantly inhibited in diabetic mice lacking the receptor for granulocyte colony-stimulating factor in their marrow-derived cells. Immunodepletion of neutrophils or monocytes inhibited the endothelial death otherwise observed when coculturing leukocytes from wild-type diabetic animals with retinal endothelium. iNOS and PARP1 are known to play a role in inflammatory processes, and we conclude that proinflammatory processes within marrow-derived cells play a central role in the development of diabetes complications in the retina and nerve. PMID:22923475

Li, Guangyuan; Veenstra, Alexander A.; Talahalli, Ramaprasad R.; Wang, Xiaoqi; Gubitosi-Klug, Rose A.; Sheibani, Nader; Kern, Timothy S.

2012-01-01

238

Growth Hormone (GH) Hypersecretion and GH Receptor Resistance in Streptozotocin Diabetic Mice in Response to a GH Secretagogue  

PubMed Central

The growth hormone (GH) and insulin-like growth factor I (IGF-I) axis were studied in streptozotocin (STZ) diabetic and nondiabetic female mice following intravenous (IV) injection of the GH secretagogue (GHS) ipamorelin or saline. On day 14, blood samples were obtained before and 10 minutes after the injection. Livers were removed and frozen for determination of the mRNA expressions of the GH receptor, GH-binding protein, and IGF-I, and hepatic IGF-I peptide. Serum samples were analyzed for GH and IGF-I. Following ipamorelin injection, the GH levels were found to be 150 ± 35 ?g/L and 62 ± 11 ?g/L in the diabetic compared to the nondiabetic mice (P < .05). Serum IGF-I levels were lower in diabetic than in nondiabetic animals, and rose after stimulation only in the nondiabetic animals. Furthermore, hepatic GH resistance and IGF-I mRNA levels and IGF-I peptide were increased in nondiabetic animals in response to GH stimulation, whereas the low levels per se of all these parameters in diabetic mice were unaffected. The study shows that STZ diabetic mice demonstrate a substantial part of the clinical features of type 1 diabetes in humans, including GH hypersecretion and GH resistance. Accordingly, it is proposed that STZ diabetic mice may be a better model of the perturbations of the GH/IGF-I axis in diabetes than STZ diabetic rats. PMID:14630569

Segev, Yael; Landau, Daniel; Phillip, Moshe; Flyvbjerg, Allan

2003-01-01

239

Anti-oxidant effect of gold nanoparticles restrains hyperglycemic conditions in diabetic mice  

PubMed Central

Background Oxidative stress is imperative for its morbidity towards diabetic complications, where abnormal metabolic milieu as a result of hyperglycemia, leads to the onset of several complications. A biological antioxidant capable of inhibiting oxidative stress mediated diabetic progressions; during hyperglycemia is still the need of the era. The current study was performed to study the effect of biologically synthesized gold nanoparticles (AuNPs) to control the hyperglycemic conditions in streptozotocin induced diabetic mice. Results The profound control of AuNPs over the anti oxidant enzymes such as GSH, SOD, Catalase and GPx in diabetic mice to normal, by inhibition of lipid peroxidation and ROS generation during hyperglycemia evidence their anti-oxidant effect during hyperglycemia. The AuNPs exhibited an insistent control over the blood glucose level, lipids and serum biochemical profiles in diabetic mice near to the control mice provokes their effective role in controlling and increasing the organ functions for better utilization of blood glucose. Histopathological and hematological studies revealed the non-toxic and protective effect of the gold nanoparticles over the vital organs when administered at dosage of 2.5 mg/kilogram.body.weight/day. ICP-MS analysis revealed the biodistribution of gold nanoparticles in the vital organs showing accumulation of AuNPs in the spleen comparatively greater than other organs. Conclusion The results obtained disclose the effectual role of AuNPs as an anti-oxidative agent, by inhibiting the formation of ROS, scavenging free radicals; thus increasing the anti-oxidant defense enzymes and creating a sustained control over hyperglycemic conditions which consequently evoke the potential of AuNPs as an economic therapeutic remedy in diabetic treatments and its complications. PMID:20630072

2010-01-01

240

The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension.  

PubMed

Diabetic nephropathy is the leading cause of end-stage renal disease in humans in the Western world. The recent development of Na+-glucose cotransporter 2 (SGLT2) inhibitors offers a new antidiabetic therapy via enhanced glucose excretion. Whether this strategy exerts beneficial effects on the development of type 2 diabetic nephropathy is still largely unclear. We investigated the effects of the specific SGLT2 inhibitor empagliflozin in BTBR.Cg-Lep/WiscJ (BTBR ob/ob) mice, which spontaneously develop type 2 diabetic nephropathy. In the first experiment, BTBR ob/ob mice received either a diet containing 300 ppm empagliflozin or equicaloric placebo chow for 12 wk. In the second experiment, BTBR ob/ob mice received 1 ?g·kg body wt(-1)·day(-1) ANG II to induce arterial hypertension and were separated into the same two diet groups for 6 wk. In both experiments, empagliflozin treatment enhanced glucosuria, thereby lowering blood glucose. Independently of hypertension, empagliflozin reduced albuminuria in diabetic mice. However, empagliflozin treatment affected diabetes-related glomerular hypertrophy, markers of renal inflammation, and mesangial matrix expansion only in BTBR ob/ob mice without hypertension. In summary, empagliflozin demonstrated significant antihyperglycemic effects, differentially ameliorating early features of diabetic nephropathy in BTBR ob/ob mice with and without hypertension. PMID:24944269

Gembardt, Florian; Bartaun, Christoph; Jarzebska, Natalia; Mayoux, Eric; Todorov, Vladimir T; Hohenstein, Bernd; Hugo, Christian

2014-08-01

241

Multi-Tissue Computational Modeling Analyzes Pathophysiology of Type 2 Diabetes in MKR Mice  

PubMed Central

Computational models using metabolic reconstructions for in silico simulation of metabolic disorders such as type 2 diabetes mellitus (T2DM) can provide a better understanding of disease pathophysiology and avoid high experimentation costs. There is a limited amount of computational work, using metabolic reconstructions, performed in this field for the better understanding of T2DM. In this study, a new algorithm for generating tissue-specific metabolic models is presented, along with the resulting multi-confidence level (MCL) multi-tissue model. The effect of T2DM on liver, muscle, and fat in MKR mice was first studied by microarray analysis and subsequently the changes in gene expression of frank T2DM MKR mice versus healthy mice were applied to the multi-tissue model to test the effect. Using the first multi-tissue genome-scale model of all metabolic pathways in T2DM, we found out that branched-chain amino acids' degradation and fatty acids oxidation pathway is downregulated in T2DM MKR mice. Microarray data showed low expression of genes in MKR mice versus healthy mice in the degradation of branched-chain amino acids and fatty-acid oxidation pathways. In addition, the flux balance analysis using the MCL multi-tissue model showed that the degradation pathways of branched-chain amino acid and fatty acid oxidation were significantly downregulated in MKR mice versus healthy mice. Validation of the model was performed using data derived from the literature regarding T2DM. Microarray data was used in conjunction with the model to predict fluxes of various other metabolic pathways in the T2DM mouse model and alterations in a number of pathways were detected. The Type 2 Diabetes MCL multi-tissue model may explain the high level of branched-chain amino acids and free fatty acids in plasma of Type 2 Diabetic subjects from a metabolic fluxes perspective. PMID:25029527

Kumar, Amit; Harrelson, Thomas; Lewis, Nathan E.; Gallagher, Emily J.; LeRoith, Derek; Shiloach, Joseph; Betenbaugh, Michael J.

2014-01-01

242

Cytochrome P450 epoxygenase CYP2J2 attenuates nephropathy in streptozotocin-induced diabetic mice  

PubMed Central

Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important and diverse roles in the cardiovascular system. The anti-inflammatory, anti-apoptotic, pro-angiogenic, and anti-hypertensive properties of EETs in the cardiovascular system suggest a beneficial role for EETs in diabetic nephropathy. This study investigated the effects of endothelial specific overexpression of the CYP2J2 epoxygenase on diabetic nephropathy in streptozotocin induced diabetic mice. Endothelial CYP2J2 overexpression attenuated renal damage as measured by urinary microalbumin and glomerulosclerosis. These effects were associated with inhibition of TGF-?/Smad signaling in the kidney. Indeed, overexpression of CYP2J2 prevented TGF-?1 induced renal tubular epithelial-mesenchymal transition in vitro. These findings highlight the bene cial roles of the CYP epoxygenase-EET system in the pathogenesis of diabetic nephropathy. PMID:21742052

Chen, Guangzhi; Wang, Peihua; Zhao, Gang; Xu, Gang; Gruzdev, Artiom; Lee, Craig R.; Zeldin, Darryl C.; Wang, Dao Wen

2011-01-01

243

Akt-mediated cardioprotective effects of aldosterone in type 2 diabetic mice.  

PubMed

Studies have shown that aldosterone would have angiogenic effects and therefore would be beneficial in the context of cardiovascular diseases. We thus investigated the potential involvement of aldosterone in triggering a cardiac angiogenic response in the context of type-2 diabetes and the molecular pathways involved. Male 3-wk-old aldosterone synthase (AS)-overexpressing mice and their control wild-type (WT) littermates were fed a standard or high-fat, high-sucrose (HFHS) diet. After 6 mo of diet treatment, mice were euthanized, and cardiac samples were assayed by RT-PCR, immunoblotting, and immunohistology. HFHS diet induced type-2 diabetes in WT (WT-D) and AS (AS-D) mice. VEGFa mRNAs decreased in WT-D (-43%, P<0.05 vs. WT) and increased in AS-D mice (+236%, P< 0.01 vs. WT-D). In WT-D mouse hearts, the proapoptotic p38MAPK was activated (P<0.05 vs. WT and AS-D), whereas Akt activity decreased (-64%, P<0.05 vs. WT). The AS mice, which exhibited a cardiac up-regulation of IGF1-R, showed an increase in Akt phosphorylation when diabetes was induced (P<0.05 vs. WT and AS-D). Contrary to WT-D mice, AS-D mouse hearts did not express inflammatory markers and exhibited a normal capillary density (P<0.05 vs. WT-D). To our knowledge, this is the first study providing new insights into the mechanisms whereby aldosterone prevents diabetes-induced cardiac disorders. PMID:24558200

Fazal, Loubina; Azibani, Feriel; Bihry, Nicolas; Coutance, Guillaume; Polidano, Evelyne; Merval, Régine; Vodovar, Nicolas; Launay, Jean-Marie; Delcayre, Claude; Samuel, Jane-Lise

2014-06-01

244

INFLUENCE OF D-Nil plus (A POLYHERBAL DRUG) ON HAEMATOLOGICAL AND BIOCHEMICAL CHANGES IN DIABETIC INDUCED RATS  

PubMed Central

Diabetes mellitus, a metabolic disorder, is characterized by hyperglycemia and altered metabolism. The administration of D-Nil plus (a polyherbal drug) showed effective treatment for alloxan induced diabetes in rats. In diabetic rats, haematological profiles namely RBC, WBC, platlet count and haemoglobin were decreased whereas ESR was increased. Similarly biochemical parameters creatinine, urea and protein were decreased but cholesterol level was increased. After the treatment with D-Nil plus, haematological parameters and biochemical parameters were reversed. The results suggest that the D-Nil plus can be used for the treatment of diabetes. PMID:22557203

Vanithamani, J.; Selvi, V.; Krishnaswamy, B. G.

2006-01-01

245

STIM1 Restores Coronary Endothelial Function in Type 1 Diabetic Mice  

PubMed Central

Rationale The endoplasmic reticulum (ER) is a major intracellular Ca2+ store in endothelial cells (ECs). The Ca2+ concentration in the ER greatly contributes to the generation of Ca2+ signals that regulate endothelial functions. Many proteins, including stromal interaction molecule 1/2 (STIM1/2), Orai1/2/3, and sarcoplasmic/ endoplasmic reticulum Ca2+-ATPase 3 (SERCA3), are involved in the ER Ca2+ refilling after store depletion in ECs. Objective This study is designed to examine the role of Ca2+ in the ER in coronary endothelial dysfunction in diabetes. Methods and Results Mouse coronary ECs (MCECs) isolated from diabetic mice exhibited (1) a significant decrease in the Ca2+ mobilization from the ER when the cells were treated by SERCA inhibitor, and (2) significant downregulation of STIM1 and SERCA3 protein expression in comparison to the controls. Overexpression of STIM1 restored (1) the increase in cytosolic Ca2+ concentration due to Ca2+ leak from the ER in diabetic MCECs, (2) the Ca2+ concentration in the ER, and (3) endothelium-dependent relaxation that was attenuated in diabetic coronary arteries. Conclusions Impaired ER Ca2+ refilling in diabetic MCECs, due to the decrease in STIM1 protein expression, attenuates endothelium-dependent relaxation in diabetic coronary arteries, while STIM1 overexpression has a beneficial and therapeutic effect on coronary endothelial dysfunction in diabetes. PMID:22896585

Estrada, Irene A.; Donthamsetty, Reshma; Debski, Patryk; Zhou, Meng-Hua; Zhang, Shenyuan L.; Yuan, Jason X.-J.; Han, Wenlong; Makino, Ayako

2013-01-01

246

Increased methylmercury toxicity related to obesity in diabetic KK-Ay mice.  

PubMed

We examined the toxic effects of methylmercury (MeHg) in KK-Ay type 2 diabetic mice to clarify how metabolic changes associated with type 2 diabetes mellitus affect MeHg toxicity. MeHg (5 mg Hg kg (-1) day(-1) p.o.) was given to 4-week-old male KK-Ay and C57BL/6J (BL/6) mice three times per week for 6 weeks. Average body weights (BW) of vehicle-treated BL/6 and KK-Ay mice were 16.3 and 16.4 g respectively on the first day, and 24.8 and 42.3 g respectively on the last day of the experiment. MeHg-treated KK-Ay mice began to lose weight about 5 weeks after MeHg administration. Six of seven MeHg-treated KK-Ay mice showed hind-limb clasping in the final stage of the experiment. The mean blood mercury level of MeHg-treated KK-Ay mice reached a maximum of 9.8 µg ml(-1) , whereas that of the MeHg-treated BL/6 mice was 2.8 µg ml(-1) after 10 days of treatment. The average total mercury concentrations in the cerebrum and epididymal fat pad were 7.4 and 0.57 µg g(-1) , respectively, for BL/6 mice and 27 and 1.6 µg g(-1) , respectively, for KK-Ay mice. In MeHg-treated KK-Ay mice with neurological symptoms, CD204-positive macrophages were observed in the brain, kidney and spleen, indicating CD204 could be a marker for injured tissues. BW loss and significant pathological changes were not observed in other groups of mice. These results indicate that body fat gain in type 2 diabetes mellitus and low mercury accumulation in adipose tissue increased MeHg concentrations in organs and enhanced toxicity in KK-Ay mice at the same dose of MeHg per BW. PMID:24243536

Yamamoto, Megumi; Yanagisawa, Rie; Motomura, Eriko; Nakamura, Masaaki; Sakamoto, Mineshi; Takeya, Motohiro; Eto, Komyo

2014-08-01

247

Knockout Mice Challenge our Concepts of Glucose Homeostasis and the Pathogenesis of Diabetes  

PubMed Central

A central component of type 2 diabetes and the metabolic syndrome is insulin resistance. Insulin exerts a multifaceted and highly integrated series of actions via its intracellular signaling systems. Generation of mice carrying null mutations of the genes encoding proteins in the insulin signaling pathway provides a unique approach to determining the role of individual proteins in the molecular mechanism of insulin action and the pathogenesis of insulin resistance and diabetes. The role of the four major insulin receptor substrates (IRS1-4) in insulin and IGF-1 signaling have been examined by creating mice with targeted gene knockouts. Each produces a unique phenotype, indicating the complementary role of these signaling components. Combined heterozygous defects often produce synergistic or epistatic effects, although the final severity of the phenotype depends on the genetic background of the mice. Conditional knockouts of the insulin receptor have also been created using the Cre-lox system. These tissue specific knockouts have provide unique insights into the control of glucose homeostasis and the pathogenesis of type 2 diabetes, and have led to development of new hypotheses about the nature of the insulin action and development of diabetes. PMID:15061645

2003-01-01

248

Diabetes in Mice With Selective Impairment of Insulin Action in Glut4-Expressing Tissues  

PubMed Central

OBJECTIVE Impaired insulin-dependent glucose disposal in muscle and fat is a harbinger of type 2 diabetes, but murine models of selective insulin resistance at these two sites are conspicuous by their failure to cause hyperglycemia. A defining feature of muscle and fat vis-à-vis insulin signaling is that they both express the insulin-sensitive glucose transporter Glut4. We hypothesized that diabetes is the result of impaired insulin signaling in all Glut4-expressing tissues. RESEARCH DESIGN AND METHODS To test the hypothesis, we generated mice lacking insulin receptors at these sites (“GIRKO” mice), including muscle, fat, and a subset of Glut4-positive neurons scattered throughout the central nervous system. RESULTS GIRKO mice develop diabetes with high frequency because of reduced glucose uptake in peripheral organs, excessive hepatic glucose production, and ?-cell failure. CONCLUSIONS The conceptual advance of the present findings lies in the identification of a tissue constellation that melds cell-autonomous mechanisms of insulin resistance (in muscle/fat) with cell-nonautonomous mechanisms (in liver and ?-cell) to cause overt diabetes. The data are consistent with the identification of Glut4 neurons as a distinct neuroanatomic entity with a likely metabolic role. PMID:21266328

Lin, Hua V.; Ren, Hongxia; Samuel, Varman T.; Lee, Hui-Young; Lu, Taylor Y.; Shulman, Gerald I.; Accili, Domenico

2011-01-01

249

Methadone ameliorates multiple-low-dose streptozotocin-induced type 1 diabetes in mice  

SciTech Connect

Type 1 diabetes is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of {beta} cells by the immune system. Opioids have been shown to modulate a number of immune functions, including T helper 1 (Th1) and T helper 2 (Th2) cytokines. The immunosuppressive effect of long-term administration of opioids has been demonstrated both in animal models and humans. The aim of this study was to determine the effect of methadone, a {mu}-opioid receptor agonist, on type 1 diabetes. Administration of multiple low doses of streptozotocin (STZ) (MLDS) (40mg/kg intraperitoneally for 5 consecutive days) to mice resulted in autoimmune diabetes. Mice were treated with methadone (10mg/kg/day subcutaneously) for 24days. Blood glucose, insulin and pancreatic cytokine levels were measured. Chronic methadone treatment significantly reduced hyperglycemia and incidence of diabetes, and restored pancreatic insulin secretion in the MLDS model. The protective effect of methadone can be overcome by pretreatment with naltrexone, an opioid receptor antagonist. Also, methadone treatment decreased the proinflammatory Th1 cytokines [interleukin (IL)-1{beta}, tumor necrosis factor-{alpha} and interferon-{gamma}] and increased anti-inflammatory Th2 cytokines (IL-4 and IL-10). Histopathological observations indicated that STZ-mediated destruction of {beta} cells was attenuated by methadone treatment. It seems that methadone as an opioid agonist may have a protective effect against destruction of {beta} cells and insulitis in the MLDS model of type 1 diabetes.

Amirshahrokhi, K.; Dehpour, A.R. [Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Hadjati, J. [Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Sotoudeh, M. [Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ghazi-Khansari, M. [Department of Pharmacology School of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)], E-mail: ghazikha@sina.tums.ac.ir

2008-10-01

250

Aqueous Extract from Pepino (Solanum muricatum Ait.) Attenuated Hyperlipidemia and Cardiac Oxidative Stress in Diabetic Mice  

PubMed Central

This study examined the lipid-lowering and cardiac protective effects of aqueous extract of pepino (Solanum muricatum Ait.) in type 2 diabetic mice. Pepino at 1, 2, or 5% was supplied for 8 weeks. Results showed that pepino significantly decreased water intake and epididymal fat pad weight in diabetic mice (P < 0.05). Pepino treatments also significantly reduced plasma glucose and insulin levels, HOMA-IR index, and improved oral glucose tolerance (P < 0.05). Plasma and hepatic levels of triglyceride and total cholesterol (TC) were higher in diabetic groups when compared with normal group (P < 0.05), pepino treatments at 2 and 5% decreased triglyceride and TC levels in both plasma and liver (P < 0.05). Diabetes enhanced mRNA expression of resistin and diacylglycerol acyltransferase1 (DGAT1) in epididymal fat pad (P < 0.05); however, pepino intake significantly suppressed mRNA expression of resistin and DGAT1 in epididymal fat pad (P < 0.05). Pepino intake significantly reduced reactive oxygen species level, increased glutathione level, and retained glutathione peroxidase and catalase activities in cardiac tissues (P < 0.05). These findings suggest that pepino could be considered as a functional food for the alleviation of type 2 diabetes. PMID:24527264

Wang, Zhi-hong; Hsu, Cheng-chin; Yin, Mei-chin

2012-01-01

251

Hypoglycemic activity of Buchholzia coriacea (Capparaceae) seeds in streptozotocin-induced diabetic rats and mice.  

PubMed

The present study evaluates the possible hypoglycemic activity and ameliorative effects of oral administration of ethanol extracts (EEBC) and butanol fraction (BFBC) of Buchholzia coriacea seeds, a plant in use traditionally for treating diabetes, hypertension, rheumatism, cold, cough and catarrh, in streptozotocin (STZ)-induced diabetic mice and rats. Fasting blood glucose (FBG) levels were evaluated before and after extracts administration. EEBC and BFBC significantly decreased (P<0.05) FBG in hyperglycemic mice and normoglycemic rats within 4 and 12 h, respectively after extract administration. The administration of EEBC, BFBC and glibenclamide (a standard antidiabetic drug) for 10 days significantly lowered (P<0.05) FBG level in STZ-induced diabetic rats by 55%, 64% and 56%, respectively. EEBC and BFBC significantly (P<0.05) decreased hepatic injury induced by STZ as evident in the decreased activity of serum alanine amino transferase and aspartate amino transferase compared to in the STZ-only treated group. Similarly, both extracts significantly decreased (P<0.05) the elevated levels of serum creatinine, urea, total cholesterol, triglyceride and thiobarbituric acid reactive species (TBARS) products in diabetic rats. Serum superoxide dismutase activity was significantly enhanced (P<0.05) by treatments with EEBC, BFBC and glibenclamide. Overall, the results suggest that B. coriacea seeds contain a potent hypoglycemic and antioxidant agent suggested to be a flavone glycoside concentrated in BFBC which may find clinical application in amelioration of diabetes-induced secondary complications. PMID:20965120

Adisa, Rahmat A; Choudhary, Mohammed I; Olorunsogo, Olufunso O

2011-11-01

252

Aqueous Extract from Pepino (Solanum muricatum Ait.) Attenuated Hyperlipidemia and Cardiac Oxidative Stress in Diabetic Mice.  

PubMed

This study examined the lipid-lowering and cardiac protective effects of aqueous extract of pepino (Solanum muricatum Ait.) in type 2 diabetic mice. Pepino at 1, 2, or 5% was supplied for 8 weeks. Results showed that pepino significantly decreased water intake and epididymal fat pad weight in diabetic mice (P < 0.05). Pepino treatments also significantly reduced plasma glucose and insulin levels, HOMA-IR index, and improved oral glucose tolerance (P < 0.05). Plasma and hepatic levels of triglyceride and total cholesterol (TC) were higher in diabetic groups when compared with normal group (P < 0.05), pepino treatments at 2 and 5% decreased triglyceride and TC levels in both plasma and liver (P < 0.05). Diabetes enhanced mRNA expression of resistin and diacylglycerol acyltransferase1 (DGAT1) in epididymal fat pad (P < 0.05); however, pepino intake significantly suppressed mRNA expression of resistin and DGAT1 in epididymal fat pad (P < 0.05). Pepino intake significantly reduced reactive oxygen species level, increased glutathione level, and retained glutathione peroxidase and catalase activities in cardiac tissues (P < 0.05). These findings suggest that pepino could be considered as a functional food for the alleviation of type 2 diabetes. PMID:24527264

Wang, Zhi-Hong; Hsu, Cheng-Chin; Yin, Mei-Chin

2012-01-01

253

Improvement of diabetes, obesity and hypertension in type 2 diabetic KKA{sup y} mice by bis(allixinato)oxovanadium(IV) complex  

SciTech Connect

Previously, we found that bis(allixinato)oxovanadium(IV) (VO(alx){sub 2}) exhibits a potent hypoglycemic activity in type 1-like diabetic mice. Since the enhancement of insulin sensitivity is involved in one of the mechanisms by which vanadium exerts its anti-diabetic effects, VO(alx){sub 2} was further tested in type 2 diabetes with low insulin sensitivity. The effect of oral administration of VO(alx){sub 2} was examined in obesity-linked type 2 diabetic KKA{sup y} mice. Treatment of VO(alx){sub 2} for 4 weeks normalized hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia and hypertension in KKA{sup y} mice; however, it had no effect on hypoadiponectinemia. VO(alx){sub 2} also improved hyperleptinemia, following attenuation of obesity in KKA{sup y} mice. This is the first example in which a vanadium compound improved leptin resistance in type 2 diabetes by oral administration. On the basis of these results, VO(alx){sub 2} is proposed to enhance not only insulin sensitivity but also leptin sensitivity, which in turn improves diabetes, obesity and hypertension in an obesity-linked type 2 diabetic animal.

Adachi, Yusuke [Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414 (Japan); Yoshikawa, Yutaka [Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414 (Japan); Yoshida, Jiro [Healthcare Institute, Wakunaga Pharmaceutical Co. Ltd, 1624 Shimokotachi, Koda-cho, Takatagun, Hiroshima 739-1195 (Japan); Kodera, Yukihiro [Healthcare Institute, Wakunaga Pharmaceutical Co. Ltd, 1624 Shimokotachi, Koda-cho, Takatagun, Hiroshima 739-1195 (Japan)]. E-mail: kodera_y@wakunaga.co.jp; Katoh, Akira [Department of Materials and Life Science, Faculty of Science and Technology, Seikei University, 3-3-1 Kitamachi, Kichijoji, Musashino-shi, Tokyo 180-8633 (Japan)]. E-mail: katoh@st.seikei.ac.jp; Takada, Jitsuya [Research Reactor Institute, Kyoto University, Osaka 590-0494 (Japan)]. E-mail: takada@hl.rri.kyoto-u.ac.jp; Sakurai, Hiromu [Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414 (Japan)]. E-mail: sakurai@mb.kyoto-phu.ac.jp

2006-07-07

254

Experimental Protection of Diabetic Mice against Lethal P. aeruginosa Infection by Bacteriophage  

PubMed Central

The emergence of antibiotic-resistant bacterial strains has become a global crisis and is vulnerable for the exploration of alternative antibacterial therapies. The present study emphasizes the use of bacteriophage for the treatment of multidrug resistant P. aeruginosa. P. aeruginosa was used to induce septicemia in streptozotocin (STZ) induced diabetic and nondiabetic mice by intraperitoneal (i.p.) injection of 3 × 108?CFU, resulting in a fatal bacteremia within 48?hrs. A single i.p. injection of 3 × 109?PFU phage GNCP showed efficient protection in both diabetic (90%) and nondiabetic (100%) bacteremic mice. It was further noted that the protection rate was reduced in diabetic mice when phage GNCP was administered after 4?h and 6?h of lethal bacterial challenge. In contrast, nondiabetic bacteremic mice were rescued even when treatment was delayed up to 20?h after lethal bacterial challenge. Evaluation of results confirmed that a single intraperitoneal injection of the phage dose (3 × 109?PFU/mL) was more effective than the multiple doses of imipenem. These results uphold the efficacy of phage therapy against pernicious P. aeruginosa infections, especially in cases of immunocompromised host. PMID:24999476

Shivshetty, Nagaveni; Hosamani, Rajeshwari; Ahmed, Liyakat; Oli, Ajay Kumar; Sannauallah, Syed; Sharanbassappa, Shivshetty; Patil, S. A.; Kelmani, Chandrakanth R.

2014-01-01

255

Maintenance of Normoglycemia in Diabetic Mice by Subcutaneous Xenografts of Encapsulated Islets  

NASA Astrophysics Data System (ADS)

The goal of islet transplantation in human diabetes is to maintain the islet grafts in the recipients without the use of immunosuppression. One approach is to encapsulate the donor islets in permselective membranes. Hollow fibers fabricated from an acrylic copolymer were used to encapsulate small numbers of rat islets that were immobilized in an alginate hydrogel for transplantation in diabetic mice. The fibers were biocompatible, prevented rejection, and maintained normoglycemia when transplanted intraperitoneally; hyperglycemia returned when the fibers were removed at 60 days. Normoglycemia was also maintained by subcutaneous implants that had an appropriately constructed outer surface on the fibers.

Lacy, Paul E.; Hegre, Orion D.; Gerasimidi-Vazeou, Andriani; Gentile, Frank T.; Dionne, Keith E.

1991-12-01

256

The effect of a saccharose-rich diet on carbohydrate and lipid metabolism of streptozotocin-diabetic rats and genetically determined 'diabetic' mice (gg-diab).  

PubMed

Streptocotocin-diabetic rats were fed with a saccharose-rich diet (68 per cent saccharose) for 37 weeks. Serum levels of insulin, triglycerides, and cholesterol were determined thereafter as well as the lesions of kidneys by histologically evaluation. For the second series of experiments, genetically determined diabetic mice (transient hyperglycemia, low k-value, but no glucosuria), were fed with the saccharose-rich diet for eight weeks. Thereafter the serum levels of insulin, triglycerides, and cholesterol were determined as well as secretion and biosynthesis of insulin of isolated pancreatic mouse islets. The metabolic parameters and the determination of the kidney lesions revealed that saccharose-feeding deteriorates the diabetic state of streptocotocin-diabetic rats: the levels of serum glucose, urine volume and urinary glucose rose rapidly in the saccharose-fed diabetic rats. These animals showed significantly higher levels of triglycerides and cholesterol after 18 and 37 weeks compared with diabetic rats fed a control diet (68 per cent starch). The kidney lesions became still more severely expressed by saccharose-rich diet. On the other hand, no major differences in the serum parameters of saccharose- or starch-fed genetically determined mice could be noticed: no manifestation of diabetes could be provoked in these latent-diabetic mice. PMID:6214518

Gonnermann, B; Schäfer-Spiegel, R; Laube, H; Schatz, H

1982-01-01

257

An aqueous extract of Portulaca oleracea ameliorates diabetic nephropathy through suppression of renal fibrosis and inflammation in diabetic db/db mice.  

PubMed

Diabetic nephropathy is one of the most common microvascular complications of diabetes and the leading cause of end-stage renal disease. In the present study, we investigated the renoprotective effect of the aqueous extract of Portulaca oleracea (AP) on diabetic nephropathy accelerated by renal fibrosis and inflammation in type 2 diabetic db/db mice. The mice were treated with AP (300 mg/kg/day, p.o.) for ten weeks to examine the long-term effects on diabetic nephropathy and renal dysfunction. We found that AP treatment markedly lowered blood glucose to 412 ± 11.4 mg/dl and plasma creatinine level to 2.3 ± 0.8 mg/dl compared to db/db mice (p < 0.05, p < 0.01, respectively). This study also showed that treatment with AP significantly decreased water intake and urine volume in diabetic db/db mice (p < 0.05). In immunohistological study, the renal expression of transforming growth factor-?1 (TGF-?1), advanced glycation end products (AGE), and intercellular adhesion molecule (ICAM)-1 markedly increased in the renal cortex of untreated db/db mice (p < 0.01). In contrast, AP treatment significantly reduced these expressions to 50 ± 2.1%, 48 ± 2.8%, 61 ± 1.1%, respectively (p < 0.01). Furthermore, NF-?B p65 activation in renal tissues markedly increased in untreated db/db mice, which was significantly suppressed by AP treatment. Taken together, these findings suggest that AP attenuates diabetic nephropathy through inhibition of renal fibrosis and inflammation in db/db mice. PMID:22745066

Lee, An Sook; Lee, Yun Jung; Lee, So Min; Yoon, Jung Joo; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

2012-01-01

258

Evaluation of Anticonvulsive Effect of Magnesium Oxide Nanoparticles in Comparison with Conventional MgO in Diabetic and Non-diabetic Male Mice  

PubMed Central

Introduction Some studies showed that magnesium has anticonvulsive effect in some animal models. Despite of the availability of well-studied anticonvulsant drugs, this evaluation was not carried on new kind of magnesium supplement, magnesium oxide nanoparticles (nMgO). According to the association between magnesium and convulsion and high prevalence of seizure and epilepsy in diabetics, this study was designed to evaluate the effect of nMgO compared to conventional MgO (cMgO) on strychnine-induced convulsion model in diabetic and non-diabetic mice. Methods Healthy male albino mice were divided into 10 groups. Diabetes mellitus was induced by streptozotocin in 5 groups. Conventional and nanoparticle MgO (5 and 10mg/kg) were administered to diabetic and non-diabetic mice, then strychnine were injected and onset of convulsions and time of death measured after strychnine administration. Results There were no significant differences between normal and diabetic groups in onset of convulsions and time of death. Pretreatment of cMgO did not have anticonvulsant effect in strychnine-induced convulsion in normal and diabetic mice. But nMgO significantly changed convulsion onset and death time after strychnine administration in normal and diabetic status (p < 0.05). Discussion According to our results, it seems that acute administration of nMgO may be important in prevention of convulsion and is more effective than its conventional form in showing anticonvulsive effect that probably is related to the physicochemical properties of nMgO, especially in diabetic subjects, a point that need further investigations. PMID:25337374

Jahangiri, Leila; Kesmati, Mahnaz; Najafzadeh, H.

2014-01-01

259

Borapetoside C from Tinospora crispa improves insulin sensitivity in diabetic mice.  

PubMed

Diabetes mellitus (DM) often leads to disability from vascular complications and neurological complications. Tinospora crispa has been widely used in Asia and Africa as a remedy for diabetes and other diseases. In this study, we investigated the hypoglycemic actions of borapetoside C isolated from T. crispa, and the mechanisms underlying its actions. Acute treatment with borapetoside C (5mg/kg, i.p.) attenuated the elevated plasma glucose induced by oral glucose in normal and type 2 DM (T2DM) mice. Compared to the effect of injected insulin (0.5 IU/kg), borapetoside C caused a more prominent increase of glycogen content in skeletal muscle of T2DM mice, but a less increase in type 1 DM (T1DM) mice. Combined treatment of a low dose borapetoside C (0.1mg/kg, i.p.) plus insulin enhanced insulin-induced lowering of the plasma glucose level and insulin-induced increase of muscle glycogen content. Continuous treatment with 5mg/kg borapetoside C (twice daily) for 7 days increased phosphorylation of insulin receptor (IR) and protein kinase B (Akt) as well as the expression of glucose transporter-2 (GLUT2) in T1DM mice. Combined treatment of a low dose borapetoside C (0.1mg/kg, twice daily) plus insulin for 7 days enhanced insulin-induced IR and Akt phosphorylation and GLUT2 expression in the liver of T1DM mice. This study proved that borapetoside C can increase glucose utilization, delayed the development of insulin resistance and enhanced insulin sensitivity. The activation of IR-Akt-GLUT2 expression and the enhancement of insulin sensitivity may contribute to the hypoglycemic action of borapetoside C in diabetic mice. PMID:22579212

Ruan, Chi-Tun; Lam, Sio-Hong; Chi, Tzong-Cherng; Lee, Shoei-Sheng; Su, Ming-Jai

2012-06-15

260

Evaluation of anti-hyperglycemic and hypoglycemic effect of Trigonella foenum- graecum Linn, Ocimum sanctum Linn and Pterocarpus marsupium Linn in normal and alloxanized diabetic rats  

Microsoft Academic Search

The hypoglycemic effect of the aqueous (Aq) extract of the bark of Pterocarpus marsupium (PM) and alcoholic (Alc) extract of seeds of Trigonella foenum-graecum (FG) and leaves of Ocimum sanctum (OS) was investigated in both normal and alloxan-induced diabetic rats. The Aq extract of PM (1 g\\/kg PO) significantly (P<0.001) reduced the blood sugar levels from 72.32±5.62 to 61.35±1.2 mg%

V Vats; J. K Grover; S. S Rathi

2002-01-01

261

Antidiabetic effects of ajoene in genetically diabetic KK-A(y) mice.  

PubMed

Antidiabetic effects of ajoene, derived from garlic, were investigated in genetically diabetic KK-A(y) mice. Four-week-old male KK-A(y) mice were kept on a laboratory diet containing 0.02 or 0.05% of ajoene for 8 wk. The elevation of water intake was suppressed depending on ajoene intake. The levels of plasma glucose in the 0.05% ajoene-containing diet group was significantly suppressed to 73.8% compared with the control group at the 8th wk. Similarly, the plasma triglyceride level was significantly suppressed. It is suggested that hyperglycemia and hypertriglyceridemia are suppressed by ajoene treatment. PMID:16392712

Hattori, Atsuhiko; Yamada, Norihiko; Nishikawa, Tomoaki; Fukuda, Hiroyuki; Fujino, Tsuchiyoshi

2005-10-01

262

Effects of cytidine 5'-diphosphocholine (CDP-choline) on the thermal nociceptive threshold in streptozotocin-induced diabetic mice.  

PubMed

Neuropathy accompanied by abnormal sensory perception is the most common complication in insulin-dependent and -independent diabetes mellitus. Since there are very few effective therapeutic regimens for sensory abnormalities in diabetes, we examined the effect of cytidine 5'-diphosphocholine (CDP)-choline on the thermal nociceptive threshold in streptozotocin-induced diabetic mice using the tail-flick test. Diabetic mice showed a shorter tail-flick latency at 1-4 weeks after streptozotocin treatment and a longer tail-flick latency after 8-12 weeks. This hyper- and hypoalgesia in diabetic mice was almost completely inhibited by daily treatment with CDP-choline (100 mg/kg/day, p.o.) beginning on the day of streptozotocin treatment. Daily treatment with CDP-choline beginning 5 weeks after streptozotocin treatment attenuated the development of hypoalgesia. Diabetic mice showed a significant increase in Na(+)-K(+)-ATPase activity at 3 weeks after streptozotocin treatment, whereas Na(+)-K(+)-ATPase activity was decreased at 12 weeks after treatment. These alterations were normalized by daily treatment with CDP-choline (100 mg/kg/day, p.o.) beginning the day of streptozotocin treatment. These results provide evidence to support the therapeutic potency of CDP-choline on the development of thermal hyper- and hypoalgesia and the progression of thermal hypoalgesia in diabetic mice. Moreover, these effects of CDP-choline may result from the normalization of Na(+)-K(+)-ATPase activity. PMID:18834878

Kamei, Junzo; Ohsawa, Masahiro; Miyata, Shigeo; Endo, Kazuki; Hayakawa, Hiroyuki

2008-11-19

263

Remodeling of cardiac cholinergic innervation and control of heart rate in mice with streptozotocin-induced diabetes  

Microsoft Academic Search

Cardiac autonomic neuropathy is a frequent complication of diabetes and often presents as impaired cholinergic regulation of heart rate. Some have assumed that diabetics have degeneration of cardiac cholinergic nerves, but basic knowledge on this topic is lacking. Accordingly, our goal was to evaluate the structure and function of cardiac cholinergic neurons and nerves in C57BL\\/6 mice with streptozotocin-induced diabetes.

Abigail M. Mabe; Donald B. Hoover

2011-01-01

264

Transgenic and Knockout Mice in Diabetes Research: Novel Insights into Pathophysiology, Limitations, and Perspectives  

NSDL National Science Digital Library

Insulin resistance and type 2 diabetes are serious public health threats. Although enormous research efforts have been focused on the pathogenesis of these diseases, the underlying mechanisms remain only partly understood. Here we review mouse phenotypes resulting from inactivation of molecules responsible for the control of glucose metabolism that have led to novel insights into insulin action and the development of insulin resistance. In addition, more sophisticated strategies to manipulate genes in mice in the future are presented.

L. Plum (University of Cologne Department of Mouse Genetics and Metabolism, Institute for Genetics)

2005-06-01

265

Acute onset of diabetic pathological changes in transgenic mice with human aldose reductase cDNA  

Microsoft Academic Search

Summary  To investigate the role of human aldose reductase (hAR) in the pathogenesis of diabetic complications, we generated transgenic mice carrying hAR cDNA driven by the murine MHC class I molecule promoter (hAR-Tg). Northern and Western blot analyses and immunoassay of hAR revealed that both hAR mRNA and the protein were expressed in all tissues tested. Thrombosis in renal vessels and

T. Yamaoka; C. Nishimura; K. Yamashita; M. Itakura; T. Yamada; J. Fujimoto; Y. Kokai

1995-01-01

266

Effects of Pravastatin on Obesity, Diabetes, and Adiponectin in Diet-induced Obese Mice  

Microsoft Academic Search

Objective:The aim of this study was to investigate the in vivo effects of pravastatin on the development of obesity and diabetes in diet-induced obese (DIO) mice.Methods and Procedures:We examined food intake, body-weight changes, visceral white adipose tissue (WAT) adiponectin and resistin levels, and energy metabolism.Results:Treatment with 100 mg\\/kg\\/day pravastatin for 28 days decreased diet-induced weight gain and visceral adiposity. In

Kana Araki; Takayuki Masaki; Isao Katsuragi; Tetsuya Kakuma; Hironobu Yoshimatsu

2008-01-01

267

CXCR4 Antagonist AMD3100 Accelerates Impaired Wound Healing in Diabetic Mice  

Microsoft Academic Search

The antagonism of CXC-chemokine receptor 4 (CXCR4) with AMD3100 improves cardiac performance after myocardial infarction by augmenting the recruitment of endothelial progenitor cells (EPCs) from the bone marrow to the regenerating vasculature. We investigated whether AMD3100 may accelerate diabetes-impaired wound healing through a similar mechanism. Skin wounds were made on the backs of leptin receptor-deficient mice and treated with AMD3100

Yukihide Nishimura; Masaaki Ii; Gangjian Qin; Hiromichi Hamada; Jun Asai; Hideya Takenaka; Haruki Sekiguchi; Marie-Ange Renault; Kentaro Jujo; Norito Katoh; Saburo Kishimoto; Aiko Ito; Christine Kamide; John Kenny; Meredith Millay; Sol Misener; Tina Thorne; Douglas W Losordo

2012-01-01

268

Immune responses to an encapsulated allogeneic islet {beta}-cell line in diabetic NOD mice  

SciTech Connect

Our goal is to develop effective islet grafts for treating type 1 diabetes. Since human islets are scarce, we evaluated the efficacy of a microencapsulated insulin-secreting conditionally transformed allogeneic {beta}-cell line ({beta}TC-tet) in non-obese diabetic mice treated with tetracycline to inhibit cell growth. Relatively low serum levels of tetracycline controlled proliferation of {beta}TC-tet cells without inhibiting effective control of hyperglycemia in recipients. There was no significant host cellular reaction to the allografts or host cell adherence to microcapsules, and host cytokine levels were similar to those of sham-operated controls. We conclude that encapsulated allogeneic {beta}-cell lines may be clinically relevant, because they effectively restore euglycemia and do not elicit a strong cellular immune response following transplantation. To our knowledge, this is First extensive characterization of the kinetics of host cellular and cytokine responses to an encapsulated islet cell line in an animal model of type 1 diabetes.

Black, Sasha P. [Charles River Laboratories, Pre-clinical Services Montreal, Senneville, Que., H9X 3R3 (Canada)]. E-mail: Sasha.Black@ca.crl.com; Constantinidis, Ioannis [Department of Medicine, Division of Endocrinology, University of Florida, Gainesville, FL 32610 (United States); Cui, Hong [Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322 (United States); Tucker-Burden, Carol [Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322 (United States); Weber, Collin J. [Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322 (United States); Safley, Susan A. [Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322 (United States)

2006-02-03

269

Role of Metformin in Suppressing 1,2-Dimethylhydrazine-Induced Colon Cancer in Diabetic and Non-Diabetic Mice: Effect on Tumor Angiogenesis and Cell Proliferation  

PubMed Central

Several studies indicated that type 2 diabetes mellitus and insulin resistance are associated with increased colon cancer risk. Recently, studies suggest that metformin can reduce cancer risk in diabetic or non-diabetic patients with unclear mechanisms. This work aimed to determine the effect of metformin on chemically-induced colon cancer in mice. Colon cancer was induced using 1,2-dimethylhydrazine (DMH, 20 mg/kg/week, s.c.) for fifteen weeks. Experiment I: healthy mice were fed with basal diet for four weeks and then allocated into seven groups, (i) saline, (ii) DMH, (iii) oxaliplatin, (iv–v): metformin (100 or 200 mg/kg) and (vi–vii): oxaliplatin+metformin (100 or 200 mg/kg), respectively. Experiment II: type 2 diabetes mellitus was induced by injection of STZ (30 mg/kg) after four weeks of high-fat feeding and then mice were allocated into seven groups similar to those reported in experiment I. Examination of the colonic tissue at the end of the experiment highlighted an increase in angiogenic markers and cell proliferation and showed a greater immunostaining for insulin growth factor I receptors and CD34 in the colon of diabetic mice compared to non-diabetics. In general, metformin downregulated tumor angiogenesis and augmented the antitumor effect of oxaliplatin. Overall, the current results showed that metformin protected against DMH-induced colon cancer in non-diabetic and diabetic mice. This therapeutic effect was, at least in part, attributed to its anti-angiogenic and anti-proliferative mechanisms. PMID:24971882

Zaafar, Dalia K.; Zaitone, Sawsan A.; Moustafa, Yasser M.

2014-01-01

270

Antidiabetic effects of SGLT2-selective inhibitor ipragliflozin in streptozotocin-nicotinamide-induced mildly diabetic mice.  

PubMed

Sodium-glucose cotransporter (SGLT) 2 plays an important role in renal glucose reabsorption, and inhibition of renal SGLT2 activity represents an innovative strategy for the treatment of hyperglycemia in diabetic patients. The present study investigated the antidiabetic effects of ipragliflozin, a SGLT2-selective inhibitor, in streptozotocin-nicotinamide-induced mildly diabetic mice, which exhibited a mild decline in glucose tolerance associated with the loss of early-phase insulin secretion. Oral administration of ipragliflozin increased urinary glucose excretion in a dose-dependent manner, an effect which was significant at doses of 0.3 mg/kg or higher and lasted over 12 h. In addition, ipragliflozin dose-dependently improved hyperglycemia and glucose intolerance with concomitant decreases in plasma insulin levels without causing hypoglycemia. Once-daily dosing of ipragliflozin (0.1 - 3 mg/kg) for 4 weeks attenuated hyperglycemia, glucose intolerance, and impaired insulin secretion. These results suggest that the SGLT2-selective inhibitor ipragliflozin increases urinary glucose excretion by inhibiting renal glucose reabsorption, improves hyperglycemia in streptozotocin-nicotinamide-induced mildly diabetic mice, and may be useful for treating type 2 diabetes. PMID:22971845

Tahara, Atsuo; Kurosaki, Eiji; Yokono, Masanori; Yamajuku, Daisuke; Kihara, Rumi; Hayashizaki, Yuka; Takasu, Toshiyuki; Imamura, Masakazu; Qun, Li; Tomiyama, Hiroshi; Kobayashi, Yoshinori; Noda, Atsushi; Sasamata, Masao; Shibasaki, Masayuki

2012-01-01

271

Effect of resveratrol on behavioral performance of streptozotocin-induced diabetic mice in anxiety tests.  

PubMed

The aim of this study was to evaluate with anxiety tests the effect of resveratrol (RSV) on streptozotocin (STZ)-induced diabetic mouse behavioral performance at the second and fourth week of treatment. Confirmed diabetic mice (>250 mg/dl of glucose in blood after STZ injection) were treated with RSV (RDM, n=12) or control treated (DM, n=12) for 4 weeks. DM and RDM were tested in the Open Field Test (OFT) and Elevated Plus Maze (EPM). In the second week of RSV treatment, a higher grooming frequency (P<0.05) and a lower defecation and rearing frequency (P<0.05) were detected in the OFT in the RDM group compared with the DM. There was a higher grooming frequency (P<0.05) and higher percentage of entries in open arms (P<0.05) in the RDM group than in the DM group in the EPM. However, in the fourth week of RSV treatment, the only effect observed was a higher grooming frequency in the RDM group than in the DM group (P<0.05) in the EPM. In conclusion, RSV treatment in diabetic mice provoked anxiolytic-like effects in both tests (OFT and EPM), and these effects were observed in a short time window (2 weeks). It is suggested that RSV may help diabetic animals to adapt to new stressing and anxiety situations and thus to improve their welfare. PMID:25077757

Damián, Juan P; Acosta, Victoria; Da Cuña, Maira; Ramírez, Isara; Oddone, Natalia; Zambrana, Ana; Bervejillo, Verónica; Benech, Juan C

2014-01-01

272

Effect of Resveratrol on Behavioral Performance of Streptozotocin-induced Diabetic Mice inAnxiety Tests  

PubMed Central

The aim of this study was to evaluate with anxiety tests the effect of resveratrol (RSV) on streptozotocin (STZ)-induced diabetic mouse behavioral performance at the second and fourth week of treatment. Confirmed diabetic mice (>250 mg/dl of glucose in blood after STZ injection) were treated with RSV (RDM, n=12) or control treated (DM, n=12) for 4 weeks. DM and RDM were tested in the Open Field Test (OFT) and Elevated Plus Maze (EPM). In the second week of RSV treatment, a higher grooming frequency (P<0.05) and a lower defecation and rearing frequency (P<0.05) were detected in the OFT in the RDM group compared with the DM. There was a higher grooming frequency (P<0.05) and higher percentage of entries in open arms (P<0.05) in the RDM group than in the DM group in the EPM. However, in the fourth week of RSV treatment, the only effect observed was a higher grooming frequency in the RDM group than in the DM group (P<0.05) in the EPM. In conclusion, RSV treatment in diabetic mice provoked anxiolytic-like effects in both tests (OFT and EPM), and these effects were observed in a short time window (2 weeks). It is suggested that RSV may help diabetic animals to adapt to new stressing and anxiety situations and thus to improve their welfare. PMID:25077757

Damián, Juan P.; Acosta, Victoria; Da Cuña, Maira; Ramírez, Isara; Oddone, Natalia; Zambrana, Ana; Bervejillo, Verónica; Benech, Juan C.

2014-01-01

273

Evaluation of Chios mastic gum on lipid and glucose metabolism in diabetic mice.  

PubMed

Chios mastic gum (MG), a resin produced from Pistacia lentiscus var. Chia, is reported to possess beneficial cardiovascular and hepatoprotective properties. This study investigated the effect of crude Chios MG on metabolic parameters in diabetic mice. Streptozotocin-induced diabetic 12-week-old male C57bl/6 mice were assigned to three groups: NC (n=9) control; LdM (n=9) animals receiving low dose mastic for 8 weeks (20?mg/kg body weight [BW]); and HdM (n=9) animals receiving high dose mastic (500?mg/kg BW) for the same period. Serum lipid and glucose levels were determined at baseline, at 4 and 8 weeks. Serum total protein, adiponectin, and resistin levels were also measured at the end of the experiment. Histopathological examination for liver, kidney, aorta, and heart lesions was performed. After 4 weeks, MG administration resulted in decreased serum glucose and triglyceride levels in both LdM and HdM, whereas BW levels were reduced in LdM group compared with controls. At the end of the experiment, LdM presented significantly lower serum glucose, cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and improved high-density lipoprotein cholesterol levels compared with control group. HdM group had ameliorated serum triglyceride levels. Hepatic steatosis observed in control group was partially reversed in LdM and HdM groups. MG administered in low dosages improves glucose and lipid disturbances in diabetic mice while alleviating hepatic damage. PMID:24404977

Georgiadis, Ioannis; Karatzas, Theodore; Korou, Laskarina-Maria; Agrogiannis, George; Vlachos, Ioannis S; Pantopoulou, Alkisti; Tzanetakou, Irene P; Katsilambros, Nikolaos; Perrea, Despina N

2014-03-01

274

Anomer-Equilibrated Streptozotocin Solution for the Induction of Experimental Diabetes in Mice (Mus musculus)  

PubMed Central

Streptozotocin is widely used to induce diabetes in laboratory animals through multiple low-dose or single high-dose intraperitoneal injections. HPLC analysis has shown that the composition of the solution may change considerably during the first 2 h after dissolution due to equilibration of the 2 anomers (? and ?) of streptozotocin. Because of the drug's alleged instability in solution, the typical recommendation is to administer streptozotocin within 10 min after dissolution. We compared the induction of diabetes in NOD/SCID mice by injection of a single high dose of freshly made or anomer-equilibrated streptozotocin solution. Solutions were prepared from dry compound containing 85% of the ? anomer, which is the more toxic of the 2. Body weight and nonfasting blood glucose levels were measured weekly for 8 wk. Both solutions induced long-term hyperglycemia, but blood glucose levels and mortality were higher and damage to pancreatic islands more pronounced in the mice receiving freshly prepared solution. A small proportion of mice did not respond in both treatment groups. If stored at 4 °C in the dark, the anomer-equilibrated solution retains its biologic activity for at least 40 d; under those conditions the streptozotocin content decreases by 0.1% daily, as determined by HPLC. Anomer-equilibrated streptozotocin solution has several practical advantages, and we recommend its use as standard for the induction of experimental diabetes because this practice may improve reproducibility and comparison of results between different laboratories. PMID:20122315

de la Garza-Rodea, Anabel S; Knaän-Shanzer, Shoshan; den Hartigh, Jan D; Verhaegen, Alphons PL; van Bekkum, Dirk W

2010-01-01

275

Selenium-enriched exopolysaccharides improve skeletal muscle glucose uptake of diabetic KKAy mice via AMPK pathway.  

PubMed

Selenium-enriched exopolysaccharides (EPS) produced by Enterobacter cloacae Z0206 have been proven to possess effect on reducing blood glucose level in diabetic mice. To investigate the specific mechanism, we studied the effects of oral supply with EPS on skeletal muscle glucose transportation and consumption in high-fat-diet-induced diabetic KKAy mice. We found that EPS supplementation increased expressions of glucose transporter 4 (Glut4), hexokinase 2 (hk2), phosphorylation of AMP-activated kinase subunit ?2 (pAMPK?2), and peroxisome proliferator-activated receptor ? coactivator 1? (PGC-1?), and increased expression of characteristic protein of oxidative fibers such as troponin I and cytochrome c (Cytc). Furthermore, we found that EPS increased glucose uptake and expressions of pAMPK?2 and PGC-1? in palmitic acid (PA)-induced C2C12 cells. However, while EPS inhibited AMPK?2 with interference RNA (iRNA), effects of EPS on the improvement of glucose uptake diminished. These results indicated that EPS may improve skeletal muscle glucose uptake of diabetic KKAy mice through AMPK?2-PGC-1? pathway. PMID:24729044

Zhou, Xihong; Chen, Jingqing; Wang, Fengqin; Yang, Hangxian; Yang, Ren; Wang, Xinxia; Wang, Yizhen

2014-06-01

276

Nearby Construction Impedes the Progression to Overt Autoimmune Diabetes in NOD Mice  

PubMed Central

Construction nearby animal houses has sporadically been reported to affect various aspects of animal health. Most of the reports have focussed on the impact on stress hormone levels and the hypersensitivity of animals relative to humans. There has also been an anecdotal report on the impact of construction on autoimmune diabetes in NOD mice. Here, we describe that nearby construction significantly impedes the progression to overt diabetes in female NOD mice offspring. We demonstrate that this was not due to a genetic drift or to particularities associated with our specific mouse colony. Interestingly, although the glycemia levels remained low in mice born from mothers subject to construction stress during gestation, we detected an active autoimmune reaction towards pancreatic islet cells, as measured by both the degree of insulitis and the presence of insulin autoantibody levels in the serum. These results suggest that the external stress imposed during embryonic development does not prevent but significantly delays the autoimmune process. Together, our findings emphasize the impact of surrounding factors during in vivo studies and are in agreement with the hypothesis that both environmental and genetic cues contribute to autoimmune diabetes development. PMID:23691516

Hillhouse, Erin E.; Chabot-Roy, Geneviève; Guyon, Marie-Josée; Tessier, Nathalie; Boulay, Maryse; Liscourt, Patricia

2013-01-01

277

CXCR4 antagonist AMD3100 accelerates impaired wound healing in diabetic mice.  

PubMed

The antagonism of CXC-chemokine receptor 4 (CXCR4) with AMD3100 improves cardiac performance after myocardial infarction by augmenting the recruitment of endothelial progenitor cells (EPCs) from the bone marrow to the regenerating vasculature. We investigated whether AMD3100 may accelerate diabetes-impaired wound healing through a similar mechanism. Skin wounds were made on the backs of leptin receptor-deficient mice and treated with AMD3100 or saline. Fourteen days after treatment, wound closure was significantly more complete in AMD3100-treated mice (AMD3100: 87.0 ± 2.6%, saline: 33.1 ± 1.8%; P<0.0001) and was accompanied by greater collagen fiber formation, capillary density, smooth muscle-containing vessel density, and monocyte/macrophage infiltration. On day 7 after treatment, AMD3100 was associated with higher circulating EPC and macrophage counts, and with significantly upregulated mRNA levels of stromal cell-derived factor 1 and platelet-derived growth factor B in the wound bed. AMD3100 also promoted macrophage proliferation and phagocytosis and the migration and proliferation of diabetic mouse primary dermal fibroblasts and 3T3 fibroblasts, which express very little CXCR4. In conclusion, a single topical application of AMD3100 promoted wound healing in diabetic mice by increasing cytokine production, mobilizing bone marrow EPCs, and enhancing the activity of fibroblasts and monocytes/macrophages, thereby increasing both angiogenesis and vasculogenesis. Not all of the AMD3100-mediated effects evolved through CXCR4 antagonism. PMID:22048734

Nishimura, Yukihide; Ii, Masaaki; Qin, Gangjian; Hamada, Hiromichi; Asai, Jun; Takenaka, Hideya; Sekiguchi, Haruki; Renault, Marie-Ange; Jujo, Kentaro; Katoh, Norito; Kishimoto, Saburo; Ito, Aiko; Kamide, Christine; Kenny, John; Millay, Meredith; Misener, Sol; Thorne, Tina; Losordo, Douglas W

2012-03-01

278

Recovery from diabetes in neonatal mice after a low-dose streptozotocin treatment  

SciTech Connect

Highlights: ? We monitored long-term beta cell regeneration in neonatal mice treated with low dose STZ. ? Low-dose STZ neonatal female mice recovered blood glucose in 150 days. ? Glucose intolerance of the STZ treated mice significantly improved in 150 days. -- Abstract: Administration of streptozotocin (STZ) induces destruction of ?-cells and is widely used as an experimental animal model of type I diabetes. In neonatal rat, after low-doses of STZ-mediated destruction of ?-cells, ?-cells regeneration occurs and reversal of hyperglycemia was observed. However, in neonatal mice, ?-cell regeneration seems to occur much slowly compared to that observed in the rat. Here, we described the time dependent quantitative changes in ?-cell mass during a spontaneous slow recovery of diabetes induced in a low-dose STZ mice model. We then investigated the underlying mechanisms and analyzed the cell source for the recovery of ?-cells. We showed here that postnatal day 7 (P7) female mice treated with 50 mg/kg STZ underwent the destruction of a large proportion of ?-cells and developed hyperglycemia. The blood glucose increased gradually and reached a peak level at 500 mg/dl on day 35–50. This was followed by a spontaneous regeneration of ?-cells. A reversal of non-fasting blood glucose to the control value was observed within 150 days. However, the mice still showed impaired glucose tolerance on day 150 and day 220, although a significant improvement was observed on day 150. Quantification of the ?-cell mass revealed that the ?-cell mass increased significantly between day 100 and day 150. On day 150 and day 220, the ?-cell mass was approximately 23% and 48.5% of the control, respectively. Of the insulin-positive cells, 10% turned out to be PCNA-positive proliferating cells. Our results demonstrated that, ?-cell duplication is one of the cell sources for ?-cell regeneration.

Kataoka, Masateru; Kawamuro, Yuki; Shiraki, Nobuaki [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan)] [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); Miki, Rika; Sakano, Daisuke [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan) [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); The Global COE Cell Fate Regulation Research and Education Unit, Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); Yoshida, Tetsu; Yasukawa, Takanori; Kume, Kazuhiko [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan)] [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); Kume, Shoen, E-mail: skume@kumamoto-u.ac.jp [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan) [Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan); The Global COE Cell Fate Regulation Research and Education Unit, Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto 860-0811 (Japan)

2013-01-18

279

Hyperalgesia in non-obese diabetic (NOD) mice: a role for the inducible bradykinin B1 receptor.  

PubMed

Most studies performed to investigate the role of the inducible bradykinin B(1) receptor in the pathology and complications of type 1 diabetes have been carried out using the model of streptozotocin (STZ)-induced diabetes. The model of spontaneous autoimmune diabetes in non-obese diabetic (NOD) mice involves a long-term inflammatory process that closely resembles the human type 1 diabetes. In the present study, we aimed at establishing the correlation between the progress of diabetic hyperalgesia and the incidence of diabetes, as a function of age, in NOD mice. We also evaluated the implication of the bradykinin B(1) receptor, a receptor up-regulated during the inflammatory progress of diabetes, in the development of diabetic hyperalgesia in NOD mice. Female NOD mice were followed up from the 4th to the 32nd week of age for the incidence of diabetes. Only NOD mice with plasma glucose concentration >20 mmol/l were considered diabetic. The nociception was assessed using the hot plate and the tail immersion pain tests and the effect of acute and chronic administration of the selective bradykinin B(1) receptor agonist, desArg(9)bradykinin and its selective antagonists, R-715 (Ac-Lys-[D-beta Nal(7), Ile(8)]desArg(9)bradykinin) and R-954 (Ac-Orn-[Oic(2), alpha-MePhe(5), D-beta Nal(7), Ile(8)]desArg(9)bradykinin), on the development of diabetic hyperalgesia was studied. Diabetic NOD mice developed a significant time-dependent hyperalgesia, as measured in both tests, starting from the 8th week of age with the maximum effect observed over 16 to 20 weeks, whereas the incidence of diabetes in the tested NOD mice was only 40.16% at the age of 16 weeks and reached a maximum of 73.23% at the age 24 weeks. Both acute and chronic administration of desArg(9)bradykinin (400 microg/kg) markedly increased the hyperalgesic activity in diabetic NOD mice in the hot plate and tail immersion nociceptive tests. The selective bradykinin B(1) receptor antagonist R-715 (400 microg/kg) and its more potent and long acting analogue R-954 (200 microg/kg), administered in acute or chronic manner, significantly attenuated diabetic hyperalgesia in NOD mice in both thermal pain tests and restored nociceptive responses to values observed in control non-diabetic siblings. Our results bring the first evidence that the development of hyperalgesia in NOD mice, a model of spontaneous type 1 diabetes, precedes the occurrence of hyperglycemia and is mediated by the bradykinin B(1) receptor. It is suggested that bradykinin B(1) receptor antagonism could become a novel therapeutic approach to the treatment of diabetic neuropathic complications. PMID:15878325

Gabra, Bichoy H; Sirois, Pierre

2005-05-01

280

Knockout of the TauT Gene Predisposes C57BL/6 Mice to Streptozotocin-Induced Diabetic Nephropathy  

PubMed Central

Diabetic nephropathy is the leading cause of end stage renal disease in the world. Although tremendous efforts have been made, scientists have yet to identify an ideal animal model that can reproduce the characteristics of human diabetic nephropathy. In this study, we hypothesize that taurine insufficiency is a critical risk factor for development of diabetic nephropathy associated with diabetes mellitus. This hypothesis was tested in vivo in TauT heterozygous (TauT+/-) and homozygous (TauT-/-) knockout in C57BL/6 background mice. We have shown that alteration of the TauT gene (also known as SLC6A6) has a substantial effect on the susceptibility to development of extensive diabetic kidney disease in both TauT+/- and TauT-/-mouse models of diabetes. These animals developed histological changes characteristic of human diabetic nephropathy that included glomerulosclerosis, nodular lesions, arteriosclerosis, arteriolar dilation, and tubulointerstitial fibrosis. Immunohistochemical staining of molecular markers of smooth muscle actin, CD34, Ki67 and collagen IV further confirmed these observations. Our results demonstrated that both homozygous and heterozygous TauT gene deletion predispose C57BL/6 mice to develop end-stage diabetic kidney disease, which closely replicates the pathological features of diabetic nephropathy in human diabetic patients. PMID:25629817

Han, Xiaobin; Patters, Andrea B.; Ito, Takashi; Schaffer, Stephen W.; Chesney, Russell W.

2015-01-01

281

Knockout of the TauT Gene Predisposes C57BL/6 Mice to Streptozotocin-Induced Diabetic Nephropathy.  

PubMed

Diabetic nephropathy is the leading cause of end stage renal disease in the world. Although tremendous efforts have been made, scientists have yet to identify an ideal animal model that can reproduce the characteristics of human diabetic nephropathy. In this study, we hypothesize that taurine insufficiency is a critical risk factor for development of diabetic nephropathy associated with diabetes mellitus. This hypothesis was tested in vivo in TauT heterozygous (TauT+/-) and homozygous (TauT-/-) knockout in C57BL/6 background mice. We have shown that alteration of the TauT gene (also known as SLC6A6) has a substantial effect on the susceptibility to development of extensive diabetic kidney disease in both TauT+/- and TauT-/-mouse models of diabetes. These animals developed histological changes characteristic of human diabetic nephropathy that included glomerulosclerosis, nodular lesions, arteriosclerosis, arteriolar dilation, and tubulointerstitial fibrosis. Immunohistochemical staining of molecular markers of smooth muscle actin, CD34, Ki67 and collagen IV further confirmed these observations. Our results demonstrated that both homozygous and heterozygous TauT gene deletion predispose C57BL/6 mice to develop end-stage diabetic kidney disease, which closely replicates the pathological features of diabetic nephropathy in human diabetic patients. PMID:25629817

Han, Xiaobin; Patters, Andrea B; Ito, Takashi; Azuma, Junichi; Schaffer, Stephen W; Chesney, Russell W

2015-01-01

282

Insulin treatment directly restores neutrophil phagocytosis and bactericidal activity in diabetic mice and thereby improves surgical site Staphylococcus aureus infection.  

PubMed

Bacterial infections, including surgical site infections (SSI), are a common and serious complication of diabetes. Staphylococcus aureus, which is eliminated mainly by neutrophils, is a major cause of SSI in diabetic patients. However, the precise mechanisms by which diabetes predisposes to staphylococcal infection are not fully elucidated. The effect of insulin on this infection is also not well understood. We therefore investigated the effect of insulin treatment on SSI and neutrophil function in diabetic mice. S. aureus was inoculated into the abdominal muscle in diabetic db/db and high-fat-diet (HFD)-fed mice with or without insulin treatment. Although the diabetic db/db mice developed SSI, insulin treatment ameliorated the infection. db/db mice had neutrophil dysfunction, such as decreased phagocytosis, superoxide production, and killing activity of S. aureus; however, insulin treatment restored these functions. Ex vivo treatment (coincubation) of neutrophils with insulin and euglycemic control by phlorizin suggest that insulin may directly activate neutrophil phagocytic and bactericidal activity independently of its euglycemic effect. However, insulin may indirectly restore superoxide production by neutrophils through its euglycemic effect. HFD-fed mice with mild hyperglycemia also developed more severe SSI by S. aureus than control mice and had impaired neutrophil phagocytic and bactericidal activity, which was improved by insulin treatment. Unlike db/db mice, in HFD mice, superoxide production was increased in neutrophils and subsequently suppressed by insulin treatment. Glycemic control by insulin also normalized the neutrophil superoxide-producing capability in HFD mice. Thus, insulin may restore neutrophil phagocytosis and bactericidal activity, thereby ameliorating SSI. PMID:23027538

Yano, Hidekazu; Kinoshita, Manabu; Fujino, Keiichi; Nakashima, Masahiro; Yamamoto, Yoritsuna; Miyazaki, Hiromi; Hamada, Koji; Ono, Satoshi; Iwaya, Keiichi; Saitoh, Daizoh; Seki, Shuhji; Tanaka, Yuji

2012-12-01

283

Hypoglycemic activity and potential mechanism of a polysaccharide from the loach in streptozotocin-induced diabetic mice.  

PubMed

The present study was designed to investigate the hypoglycemic activity and the potential mechanisms of Misgurnus anguillicaudatus polysaccharide (MAP) in streptozotocin-induced diabetic mice. MAP oral administration significantly decreased the blood levels of glucose, TC, TG, LDL-C, and increased the blood levels of HDL-C and insulin in diabetic mice, concurrent with increases in body weights and pancreatic insulin contents. Moreover, MAP reversed the increased mRNA expressions of PEPCK and the reduced glycogen contents in the liver of diabetic mice. Concurrently, MAP exhibited potent anti-inflammatory and anti-oxidative activities, as evidenced by the decreased blood levels of TNF-?, IL-6, monocyte chemoattractant protein-1, MDA, and also the elevated SOD and GPx activities in the serum of diabetic mice. Furthermore, MAP also significantly improved the blood markers of the impaired liver function and renal function in diabetic mice. Altogether, these results suggest that MAP may be a potential therapeutic option for type 1 diabetes. PMID:25659690

Zhou, Jun; Yan, Junyan; Bai, Zhaoshuai; Li, Kaicheng; Huang, Kaixun

2015-05-01

284

Experimental Induction of Type 2 Diabetes in Aging-Accelerated Mice Triggered Alzheimer-Like Pathology and Memory Deficits  

PubMed Central

Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-?, dysregulated tau-phosphorylating glycogen synthase kinase 3?, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD. PMID:24121970

Mehla, Jogender; Chauhan, Balwantsinh C.; Chauhan, Neelima B.

2014-01-01

285

Short-term subcutaneous insulin treatment delays but does not prevent diabetes in NOD mice.  

PubMed

Despite encouraging results in the NOD mouse, type 1 diabetes prevention trials using subcutaneous insulin have been unsuccessful. To explain these discrepancies, 3-week-old NOD mice were treated for 7 weeks with subcutaneous insulin at two different doses: a high dose (0.5 U/mouse) used in previous mouse studies; and a low dose (0.005 U/mouse) equivalent to that used in human trials. Effects on insulitis and diabetes were monitored along with immune and metabolic modifications. Low-dose insulin did not have any effect on disease incidence. High-dose treatment delayed but did not prevent diabetes, with reduced insulitis reappearing once insulin discontinued. This effect was not associated with significant immune changes in islet infiltrates, either in terms of cell composition or frequency and IFN-? secretion of islet-reactive CD8(+) T cells recognizing the immunodominant epitopes insulin B(15-23) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)(206-214). Delayed diabetes and insulitis were associated with lower blood glucose and endogenous C-peptide levels, which rapidly returned to normal upon treatment discontinuation. In conclusion, high- but not low-dose prophylactic insulin treatment delays diabetes onset and is associated with metabolic changes suggestive of ?-cell "rest" which do not persist beyond treatment. These findings have important implications for designing insulin-based prevention trials. PMID:22678909

Brezar, Vedran; Culina, Slobodan; Gagnerault, Marie-Claude; Mallone, Roberto

2012-06-01

286

Expression of gluconeogenic enzymes and 11?-hydroxysteroid dehydrogenase type 1 in liver of diabetic mice after acute exercise  

PubMed Central

During acute exercise, normoglycemia is maintained by a precise match between hepatic glucose production and its peripheral utilization. This is met by a complex interplay of hepatic responses and glucose uptake by muscle. However, the effect of a single bout of exercise on hepatic gluconeogenesis, corticosterone (CORT) secretion, and glucose homeostasis in the db/db mouse model of type 2 diabetes is poorly understood. Diabetic db/db and lean control littermates were subjected to a 30 minute session of treadmill running and sacrificed either immediately after exercise or 8 hours later. Plasma glucose levels were markedly increased in db/db mice after exercise, whereas no change in glucose was observed in lean mice. Post-exercise measurements revealed that plasma CORT levels were also significantly increased in db/db mice compared to lean mice. Plasma hypothalamic corticotropin releasing hormone and pituitary adrenocorticotropic hormone levels were reciprocally decreased in both db/db and lean mice after exercise, indicating intact feedback mechanisms. Protein expression, determined by Western blot analysis, of the glucocorticoid receptor in liver was significantly increased in db/db mice subjected to prior exercise. In liver of db/db mice, a significant increase in the expression of phosphoenolpyruvate carboxykinase was noted compared to lean mice after exercise. However, no change in the expression of glucose-6-phosphatase (G6Pase) ? or ? was observed in db/db mice. Expression of 11?-hydroxysteroid dehydrogenase type 1 was increased significantly in db/db mice compared to lean mice after exercise. Our results show differences in plasma glucose and protein expression of gluconeogenic enzymes after acute exercise between lean and diabetic db/db mice. The db/db diabetic mouse is hyperglycemic after acute exercise. This hyperglycemic state may be explained, in part, by enhanced endogenous CORT secretion and regulated hepatic phosphoenolpyruvate carboxykinase and 11?-hydroxysteroid dehydrogenase type 1 protein expression. PMID:25364268

Brust, Korie B; Corbell, Kathryn A; Al-Nakkash, Layla; Babu, Jeganathan Ramesh; Broderick, Tom L

2014-01-01

287

Expression of gluconeogenic enzymes and 11?-hydroxysteroid dehydrogenase type 1 in liver of diabetic mice after acute exercise.  

PubMed

During acute exercise, normoglycemia is maintained by a precise match between hepatic glucose production and its peripheral utilization. This is met by a complex interplay of hepatic responses and glucose uptake by muscle. However, the effect of a single bout of exercise on hepatic gluconeogenesis, corticosterone (CORT) secretion, and glucose homeostasis in the db/db mouse model of type 2 diabetes is poorly understood. Diabetic db/db and lean control littermates were subjected to a 30 minute session of treadmill running and sacrificed either immediately after exercise or 8 hours later. Plasma glucose levels were markedly increased in db/db mice after exercise, whereas no change in glucose was observed in lean mice. Post-exercise measurements revealed that plasma CORT levels were also significantly increased in db/db mice compared to lean mice. Plasma hypothalamic corticotropin releasing hormone and pituitary adrenocorticotropic hormone levels were reciprocally decreased in both db/db and lean mice after exercise, indicating intact feedback mechanisms. Protein expression, determined by Western blot analysis, of the glucocorticoid receptor in liver was significantly increased in db/db mice subjected to prior exercise. In liver of db/db mice, a significant increase in the expression of phosphoenolpyruvate carboxykinase was noted compared to lean mice after exercise. However, no change in the expression of glucose-6-phosphatase (G6Pase) ? or ? was observed in db/db mice. Expression of 11?-hydroxysteroid dehydrogenase type 1 was increased significantly in db/db mice compared to lean mice after exercise. Our results show differences in plasma glucose and protein expression of gluconeogenic enzymes after acute exercise between lean and diabetic db/db mice. The db/db diabetic mouse is hyperglycemic after acute exercise. This hyperglycemic state may be explained, in part, by enhanced endogenous CORT secretion and regulated hepatic phosphoenolpyruvate carboxykinase and 11?-hydroxysteroid dehydrogenase type 1 protein expression. PMID:25364268

Brust, Korie B; Corbell, Kathryn A; Al-Nakkash, Layla; Babu, Jeganathan Ramesh; Broderick, Tom L

2014-01-01

288

Anti-Diabetic Effect of Balanced Deep-Sea Water and Its Mode of Action in High-Fat Diet Induced Diabetic Mice  

PubMed Central

In this study, we investigated the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. BDSW was prepared by mixing deep-sea water (DSW) mineral extracts and desalinated water to give a final hardness of 500–2000. Mice given an HFD with BDSW showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that BDSW improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that BDSW recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, ?-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with BDSW. BDSW increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. BDSW stimulated phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that BDSW has potential as an anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake. PMID:24172214

Ha, Byung Geun; Shin, Eun Ji; Park, Jung-Eun; Shon, Yun Hee

2013-01-01

289

Impaired Oral Tolerance Induction in Diabetes Prone but not in Diabetes Resistant Mice Revealed by Cholera Toxin Subunit B-Peptide Fusion Proteins  

PubMed Central

The B subunit of cholera toxin (CTB) has been used as adjuvant to improve oral vaccine delivery in type 1 diabetes. The effect of CTB/peptide formulations on antigen-specific CD4 T cells has remained largely unexplored. We investigated by tetramer analysis how oral delivery of CTB fused to 2 CD4 T cell epitopes, the BDC-2.5 T cell 2.5mi mimotope and glutamic acid decarboxylase (GAD) 286–300, affected diabetogenic CD4 T cells in NOD mice. CTB-2.5mi activated 2.5mi+ T cells when administered intraperitoneally and generated Ag-specific Foxp3+ Treg and Th2 cells following intragastric delivery. While 2.5mi+ and GAD-specific T cells were tolerized in diabetes resistant NODxB6.Foxp3EGFP F1 and NOR mice, this did not occur in NOD mice. This indicated NOD mice had a recessive genetic resistance to induce oral tolerance to both CTB-fused epitopes. Contrarily to NODxB6.Foxp3EGFP F1 mice, oral treatment in NOD mice lead to strong 2.5mi+ T cell activation and the sequestration of these cells to the effector-memory pool. Oral treatment of NOD mice with CTB-2.5mi failed to prevent diabetes. These findings underline the importance of investigating the effect of oral vaccine formulations on diabetogenic T cells as in selected cases they may have counterproductive consequences in human patients. PMID:23925934

Presa, Maximiliano; Ortiz, Angela Zarama; Garabatos, Nahir; Izquierdo, Cristina; Rivas, Elisa I.; Teyton, Luc; Mora, Conchi; Serreze, David; Stratmann, Thomas

2013-01-01

290

Artemisia campestris leaf extract alleviates early diabetic nephropathy in rats by inhibiting protein oxidation and nitric oxide end products.  

PubMed

Chronic hyperglycemia in diabetes leads to free radicals overproduction, which contributes to the development of diabetic nephropathy. The present study investigated the effects of Artemisia campestris (Ac), a plant of the Asteraceae family, on renal impairment and oxidative stress in alloxan-induced diabetic rats. Diabetes was induced by a single subcutaneous injection of alloxan (120 mg kg(-1)) in rats. Ac (200 mg kg(-1)) was administered to diabetic rats for 3 weeks. Diabetic renal injury was associated with hyperglycemia, increased serum creatinine, urea and uric acid levels. This nephropathophysiology was associated with a surproduction of nitric oxide (NO), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels and a decrease in glutathione (GSH) levels. In addition, hyperglycemia increased the activities of antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), in the kidney of diabetic rats. Treatment with Ac effectively ameliorated diabetic renal dysfunction by reducing oxidative and nitrosative stress. Histological studies also supported the experimental findings. The results suggested that Ac might act as a beneficial agent against renal dysfunctions developed in alloxan-induced diabetes. PMID:22361035

Sefi, Mediha; Fetoui, Hamadi; Soudani, Nejla; Chtourou, Yassine; Makni, Mohamed; Zeghal, Najiba

2012-03-15

291

Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)  

PubMed Central

Background Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI) and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes. Methods Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19–25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks) in diabetic mice and age-matched controls. Results After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV) wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction. Conclusion Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy. PMID:17309798

Yu, Xichun; Tesiram, Yasvir A; Towner, Rheal A; Abbott, Andrew; Patterson, Eugene; Huang, Shijun; Garrett, Marion W; Chandrasekaran, Suresh; Matsuzaki, Satoshi; Szweda, Luke I; Gordon, Brian E; Kem, David C

2007-01-01

292

Anti-diabetic properties of a non-conventional radical scavenger, as compared to pioglitazone and exendin-4, in streptozotocin-nicotinamide diabetic mice.  

PubMed

We previously showed that the innovative radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) improves metabolic dysfunctions in a diabetic mouse model. Here, we compared the in vivo effects of IAC with those of the anti-diabetic drugs pioglitazone (PIO) and exendin-4 (EX-4). Diabetes was induced in C57Bl/6J mice by streptozotocin and nicotinamide administration. Paralleled by healthy controls, diabetic animals (D) were randomly assigned to four groups and treated daily for 7 consecutive weeks: D+saline, ip; D+IAC 30mg/kgb.w., ip; D+PIO 10mg/kgb.w. per os; and D+EX-4, 50?g/kgb.w., ip. Our results show that IAC reduced basal hyperglycemia and improved glucose tolerance better than PIO or EX-4. Interestingly, in the heart of diabetic mice, IAC treatment normalized the increased levels of GSSG/GSH ratio and thiobarbituric acid reactive substances, indexes of oxidative stress and damage, while PIO and EX-4 were less effective. As supported by immunohistochemical data, IAC markedly prevented diabetic islet ?-cell reduced density, differently from PIO and EX-4 that had only a moderate effect. Interestingly, in diabetic animals, IAC treatment enhanced the activity of pancreatic-duodenal homeobox 1 (PDX-1), an oxidative stress-sensitive transcription factor essential for maintenance of ?-cell function, as evaluated by quantification of its nuclear immunostaining, whereas PIO or EX-4 treatments did not. Altogether, these observations support the improvement of the general redox balance and ?-cell function induced by IAC treatment in streptozotocin-nicotinamide diabetic mice. Furthermore, in this model, the correction of diabetic alterations was better obtained by treatment with the radical scavenger IAC than with pioglitazone or exendin-4. PMID:24530416

Novelli, Michela; Canistro, Donatella; Martano, Manuela; Funel, Niccola; Sapone, Andrea; Melega, Simone; Masini, Matilde; De Tata, Vincenzo; Pippa, Anna; Vecoli, Cecilia; Campani, Daniela; De Siena, Rocco; Soleti, Antonio; Paolini, Moreno; Masiello, Pellegrino

2014-04-15

293

Omega-3 polyunsaturated fatty acids preserve retinal function in type 2 diabetic mice  

PubMed Central

Objective: Diabetic retinopathy (DR) is associated with hyperglycemia-driven microvascular pathology and neuronal compromise in the retina. However, DR is also linked to dyslipidemia. As omega-3 (?-3) polyunsaturated fatty acids (PUFAs) are protective in proliferative retinopathy, we investigated the capacity of ?-3PUFAs to preserve retinal function in a mouse model of type 2 diabetes mellitus (T2DM). Design: Male leptin-receptor-deficient (db/db) mice were maintained for 22 weeks (4 weeks–26 weeks of life) on calorically and compositionally matched diets, except for 2% enrichment in either ?-3 or ?-6PUFAs. Visual function was assessed at 9, 14 and 26 weeks by electroretinography. Retinal capillary and neuronal integrity, as well as glucose challenge responses, were assessed on each diet. Results: The ?-3PUFA diet significantly preserved retinal function in the mouse model of T2DM to levels similar to those observed in nondiabetic control mice on normal chow. Conversely, retinal function gradually deteriorated in db/db mice on a ?-6PUFA-rich diet. There was also an enhanced ability of ?-3PUFA-fed mice to respond to glucose challenge. The protection of visual function appeared to be independent of cytoprotective or anti-inflammatory effects of ?-3PUFAs. Conclusion: This study identifies beneficial effects of dietary ?-3PUFAs on visual function in T2DM. The data are consistent with dyslipidemia negatively impacting retinal function. As ?-3PUFA lipid dietary interventions are readily available, safe and inexpensive, increasing ?-3PUFA intake in diabetic patients may slow the progression of vision loss in T2DM. PMID:23448719

Sapieha, P; Chen, J; Stahl, A; Seaward, M R; Favazza, T L; Juan, A M; Hatton, C J; Joyal, J-S; Krah, N M; Dennison, R J; Tang, J; Kern, T S; Akula, J D; Smith, L E H

2012-01-01

294

Immunomodulation therapy of diabetes by oral administration of a surfactin lipopeptide in NOD mice.  

PubMed

Type 1 diabetes mellitus (T1DM) is considered an autoimmune disease, which can be attenuated by modulation of immune pathway from Th1- to Th2-type through vaccination. WH1fungin surfactin is a Bacillus-produced natural immunomodulator. NOD mice were orally treated with 5mg/kg or 25mg/kg WH1fungin once a week for total 4 weeks. After the final administration, the diabetes incidence and the anti-inflammatory roles of WH1fungin were investigated by immunohistochemistry, FACS and ELISA. The results showed oral WH1fungin obviously resulted in a WH1fungin-unspecific suppression of T1DM. Diabetes incidence was significantly reduced when compared to phosphate buffered saline (PBS) control. Mice in the control group began to be onset of diabetes at week 15, following with an increased mortality from week 16 to 28. At the end of observation, the diabetes incidence reached to 81% at week 30, while only 25% in WH1fungin groups. The splenocytes assay showed oral WH1fungin could suppress T cells proliferation, down-regulate amounts of activated CD8(+) T cells with the production of tumor necrosis factor (TNF)-? and interferon (IFN)-?, and increase CD4(+)CD25(+)FOXP3(+) regulator T cells (Tregs). The serum assay revealed oral WH1fungin down-regulated TNF-? and IgG2a but increased interleukin (IL)-10 and IgG1 in mice. All of these data showed oral WH1fungin tended to switch the immune response from Th1- to Th2-type. The further surveys revealed that less IFN-? but more transfer growth factor (TGF)-? were found in the islets of mice with oral WH1fungin when compared to that in the control group. As a result, the normal islet architecture and slight inflammatory cells infiltration was observed with a slight insulitis in the oral WH1fungin groups. These results demonstrate that oral WH1fungin might be a novel therapeutic approach for the prevention of T1DM. PMID:25239487

Gao, Zhenqiu; Zhao, Xiuyun; Yang, Tao; Shang, Jun; Shang, Long; Mai, Haizhe; Qi, Gaofu

2014-11-28

295

Prevention or Early Cure of Type 1 Diabetes by Intranasal Administration of Gliadin in NOD Mice  

PubMed Central

Induction of long-term tolerance to ?-cell autoantigens has been investigated both in animal models and in human type 1 diabetes (T1D) in order to prevent the disease. As regards external compounds, the dietary plant protein fraction has been associated with high penetrance of the disease, whereas gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis was lowered. Intranasal gliadin also rescued a fraction of prediabetic 13-week-old NOD mice from progressing to clinical onset of diabetes compared to OVA-treated controls. Vaccination with i.n. gliadin led to an induction of CD4+Foxp3+ T cells and even more significant induction of ?? T cells in mucosal, but not in non-mucosal lymphoid compartments. This prevention strategy was characterized by an increased proportion of IL-10 and a decreased proportion of IL-2, IL-4 and IFN-?-positive CD4+Foxp3+ T cells, and IFN-?-positive ?? T cells, preferentially in mucosal lymphoid organs. In conclusion, i.n. vaccination with gliadin, an environmental antigen with possible etiological influence in T1D, may represent a novel, safer strategy for prevention or even early cure of T1D. PMID:24728138

Funda, David P.; Fundova, Petra; Hansen, Axel Kornerup; Buschard, Karsten

2014-01-01

296

Low-Intensity Vibration Improves Angiogenesis and Wound Healing in Diabetic Mice  

PubMed Central

Chronic wounds represent a significant health problem, especially in diabetic patients. In the current study, we investigated a novel therapeutic approach to wound healing – whole body low-intensity vibration (LIV). LIV is anabolic for bone, by stimulating the release of growth factors, and modulating stem cell proliferation and differentiation. We hypothesized that LIV improves the delayed wound healing in diabetic mice by promoting a pro-healing wound environment. Diabetic db/db mice received excisional cutaneous wounds and were subjected to LIV (0.4 g at 45 Hz) for 30 min/d or a non-vibrated sham treatment (controls). Wound tissue was collected at 7 and 15 d post-wounding and wound healing, angiogenesis, growth factor levels and wound cell phenotypes were assessed. LIV increased angiogenesis and granulation tissue formation at day 7, and accelerated wound closure and re-epithelialization over days 7 and 15. LIV also reduced neutrophil accumulation and increased macrophage accumulation. In addition, LIV increased expression of pro-healing growth factors and chemokines (insulin-like growth factor-1, vascular endothelial growth factor and monocyte chemotactic protein-1) in wounds. Despite no evidence of a change in the phenotype of CD11b+ macrophages in wounds, LIV resulted in trends towards a less inflammatory phenotype in the CD11b? cells. Our findings indicate that LIV may exert beneficial effects on wound healing by enhancing angiogenesis and granulation tissue formation, and these changes are associated with increases in pro-angiogenic growth factors. PMID:24618702

Weinheimer-Haus, Eileen M.; Judex, Stefan; Ennis, William J.; Koh, Timothy J.

2014-01-01

297

Renal protective effects of extracts from guava fruit (Psidium guajava L.) in diabetic mice.  

PubMed

This study analyzed the content of phenolic acids and flavonoids in extracts of guava fruit (Psidium guajava L.), and examined the renal protective effects of guava aqueous extract (GAE) and ethanol extract (GEE) in diabetic mice. GAE had more caffeic acid, myricetin, and quercetin; and GEE had more cinnamic, coumaric and ferulic acids. GAE or GEE at 1 and 2 % was supplied in diet for 12 weeks. GAE or GEE intake at 2 % significantly reduced glucose and blood urea nitrogen levels, increased insulin level in plasma of diabetic mice (p?diabetic progression via its anti-oxidative, anti-inflammatory and anti-glycative effects. PMID:22581156

Lin, Chia-Yu; Lin, Chia-Yun; Yin, Mei-Chin

2012-09-01

298

The anti-diabetic effects and pharmacokinetic profiles of berberine in mice treated with Jiao-Tai-Wan and its compatibility.  

PubMed

Jiao-Tai-Wan (JTW), a classical Chinese prescription, has been clinically employed to treat diabetes mellitus in recent years. To investigate the comparative evaluations on anti-diabetic effects and pharmacokinetics of the active ingredient berberine in mice treated with JTW in various combinations of its constituent herbs. In our study, the anti-diabetic study was carried out in diabetic mice induced by intraperitoneal injection of streptozotocin. The diabetic mice were randomly assigned to three therapy groups and orally administered with different prescription proportions of Rhizoma Coptidis and Cinnamomum cassia respectively. The level of plasma glucose, lipid profile and parameters related to oxidative stress were determined. The concentrations of berberine in non-diabetic mice plasma were determined using HPLC, and main pharmacokinetic parameters were investigated. The results indicated that the compatibility effects of ingredients present in Cinnamomum cassia could affect the anti-diabetic ability and pharmacokinetics of berberine in JTW. PMID:23582408

Chen, Guang; Lu, Fuer; Xu, Lijun; Dong, Hui; Yi, Ping; Wang, Fang; Huang, Zhaoyi; Zou, Xin

2013-07-15

299

Inhibition of Kidney Proximal Tubular Glucose Reabsorption Does Not Prevent against Diabetic Nephropathy in Type 1 Diabetic eNOS Knockout Mice  

PubMed Central

Background and Objective Sodium glucose cotransporter 2 (SGLT2) is the main luminal glucose transporter in the kidney. SGLT2 inhibition results in glycosuria and improved glycaemic control. Drugs inhibiting this transporter have recently been approved for clinical use and have been suggested to have potential renoprotective benefits by limiting glycotoxicity in the proximal tubule. We aimed to determine the renoprotective benefits of empagliflozin, an SGLT2 inhibitor, independent of its glucose lowering effect. Research Design and Methods We induced diabetes using a low dose streptozotocin protocol in 7–8 week old endothelial nitric oxide (eNOS) synthase knockout mice. We measured fasting blood glucose on a monthly basis, terminal urinary albumin/creatinine ratio. Renal histology was assessed for inflammatory and fibrotic changes. Renal cortical mRNA transcription of inflammatory and profibrotic cytokines, glucose transporters and protein expression of SGLT2 and GLUT1 were determined. Outcomes were compared to diabetic animals receiving the angiotensin receptor blocker telmisartan (current best practice). Results Diabetic mice had high matched blood glucose levels. Empagliflozin did not attenuate diabetes-induced albuminuria, unlike telmisartan. Empagliflozin did not improve glomerulosclerosis, tubular atrophy, tubulointerstitial inflammation or fibrosis, while telmisartan attenuated these. Empagliflozin did not modify tubular toll-like receptor-2 expression in diabetic mice. Empagliflozin did not reduce the upregulation of macrophage chemoattractant protein-1 (MCP-1), transforming growth factor ?1 and fibronectin mRNA observed in the diabetic animals, while telmisartan decreased transcription of MCP-1 and fibronectin. Empagliflozin increased GLUT1 mRNA expression and telmisartan increased SGLT2 mRNA expression in comparison to untreated diabetic mice. However no significant difference was found in protein expression of GLUT1 or SGLT2 among the different groups. Conclusion Hence SGLT2 inhibition does not have renoprotective benefits independent of glucose lowering. PMID:25369239

Gangadharan Komala, Muralikrishna; Gross, Simon; Mudaliar, Harshini; Huang, Chunling; Pegg, Katherine; Mather, Amanda; Shen, Sylvie; Pollock, Carol A.; Panchapakesan, Usha

2014-01-01

300

Effects of two antioxidants; ?-lipoic acid and fisetin against diabetic cataract in mice.  

PubMed

The purpose of this study was to determine whether ?-lipoic acid and fisetin have protective effects against cataract in a streptozotocin-induced experimental cataract model. Twenty-eight male BALB/C mice were made diabetic by the intraperitoneal administration of streptozotocin (200 mg/kg). Three weeks after induction of diabetes, mice were divided randomly into 4 groups in which each group contained 7 mice; fisetin-treated group (group 1), ?-lipoic acid-treated group (group 2), fisetin placebo group (group 3), ?-lipoic acid placebo group (group 4). Fisetin and ?-lipoic acid were administered intraperitoneally weekly for 5 weeks. Cataract development was assessed at the end of 8 weeks by slit lamp examination, and cataract formation was graded using a scale. All groups developed at least grade 1 cataract formation. In the fisetin-treated group, the cataract stages were significantly lower than in the placebo group (p = 0.02). In the ?-lipoic acid-treated group, the cataract stages were lower than in the placebo group but it did not reach to a significant value. Both fisetin and ?-lipoic acid had a protective effect on cataract development in a streptozotocin-induced experimental cataract model. The protective effect of fisetin appears as though more effective than ?-lipoic acid. PMID:25488016

Kan, Emrah; Kiliçkan, Elif; Ayar, Ahmet; Colak, Ramis

2014-12-01

301

Transplantation of bone marrow derived cells promotes pancreatic islet repair in diabetic mice  

SciTech Connect

The transplantation of bone marrow (BM) derived cells to initiate pancreatic regeneration is an attractive but as-yet unrealized strategy. Presently, BM derived cells from green fluorescent protein transgenic mice were transplanted into diabetic mice. Repair of diabetic islets was evidenced by reduction of hyperglycemia, increase in number of islets, and altered pancreatic histology. Cells in the pancreata of recipient mice co-expressed BrdU and insulin. Double staining revealed {beta} cells were in the process of proliferation. BrdU{sup +} insulin{sup -} PDX-1{sup +} cells, Ngn3{sup +} cells and insulin{sup +} glucagon{sup +} cells, which showed stem cells, were also found during {beta}-cell regeneration. The majority of transplanted cells were mobilized to the islet and ductal regions. In recipient pancreas, transplanted cells simultaneously expressed CD34 but did not express insulin, PDX-1, Ngn3, Nkx2.2, Nkx6.1, Pax4, Pax6, and CD45. It is concluded that BM derived cells especially CD34{sup +} cells can promote repair of pancreatic islets. Moreover, both proliferation of {beta} cells and differentiation of pancreatic stem cells contribute to the regeneration of {beta} cells.

Gao Xiaodong; Song Lujun; Shen Kuntang; Wang Hongshan [Department of General Surgery, Center Laboratory of Surgery, Zhongshan Hospital, Shanghai Medical School, Fudan University, 180, Fenglin Road, Shanghai 200032 (China); Niu Weixin [Department of General Surgery, Center Laboratory of Surgery, Zhongshan Hospital, Shanghai Medical School, Fudan University, 180, Fenglin Road, Shanghai 200032 (China)], E-mail: niu.weixin@zs-hospital.sh.cn; Qin Xinyu [Department of General Surgery, Center Laboratory of Surgery, Zhongshan Hospital, Shanghai Medical School, Fudan University, 180, Fenglin Road, Shanghai 200032 (China)], E-mail: qin.xinyu@zs-hospital.sh.cn

2008-06-20

302

Effects of buckwheat sprouts on plasma and hepatic parameters in type 2 diabetic db/db mice.  

PubMed

We examined the effects of buckwheat sprouts (BS) (Fagopyrum esculentum Moench) on lipid and carbohydrate metabolism and on in vivo oxidative stress in type 2 diabetic mice. Mice (C57BL/KsJ-lepr(db)/lepr(db), db/db) were fed a diet containing 0%, 5%, or 10% BS based on AIN-93G for 21 d. Plasma parameters, such as total cholesterol, arteriosclerotic index, thiobarbituric acid reactive substances (TBARS), and the HbA1c concentration of whole blood in the diabetic BS-fed groups were lower than those in the diabetic control (AIN-93G) group. Concentrations of hepatic parameters, such as lipids, total cholesterol, triglyceride, and TBARS levels in BS-fed groups, were lower than those in the diabetic control group. Although gene expressions of the hepatic lipid regulation enzymes such as 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoAR) and cholesterol 7?-hydroxylase (CYP7A1) in diabetic BS-fed groups were higher than in the diabetic control group, the elevation of mRNA level of CYP7A1 was greater than that of HMG-CoAR. In addition, concentration of bile acids in feces was higher in the diabetic BS-fed groups than in the diabetic control group. These results suggest that BS have various in vivo activities in relation to antidiabetic effects in type 2 diabetic mice, especially for improvement in lipid metabolism. It was deduced that excretion of bile acids in feces by feeding the BS diet would contribute to the suppression of the cholesterol concentration in the plasma and liver tissues of mice. PMID:21535603

Watanabe, Mitsuru; Ayugase, Jun

2010-01-01

303

Urtica dioica extract attenuates depressive like behavior and associative memory dysfunction in dexamethasone induced diabetic mice.  

PubMed

Evidences suggest that glucocorticoids results in depression and is a risk factor for type 2 diabetes. Further diabetes induces oxidative stress and hippocampal dysfunction resulting in cognitive decline. Traditionally Urtica dioica has been used for diabetes mellitus and cognitive dysfunction. The present study investigated the effect of the hydroalcoholic extract of Urtica dioica leaves (50 and 100 mg/kg, p.o.) in dexamethasone (1 mg/kg, i.m.) induced diabetes and its associated complications such as depressive like behavior and cognitive dysfunction. We observed that mice administered with chronic dexamethasone resulted in hypercortisolemia, oxidative stress, depressive like behavior, cognitive impairment, hyperglycemia with reduced body weight, increased water intake and decreased hippocampal glucose transporter-4 (GLUT4) mRNA expression. Urtica dioica significantly reduced hyperglycemia, plasma corticosterone, oxidative stress and depressive like behavior as well as improved associative memory and hippocampal GLUT4 mRNA expression comparable to rosiglitazone (5 mg/kg, p.o.). Further, Urtica dioica insignificantly improved spatial memory and serum insulin. In conclusion, Urtica dioica reversed dexamethasone induced hyperglycemia and its associated complications such as depressive like behavior and cognitive dysfunction. PMID:24435938

Patel, Sita Sharan; Udayabanu, Malairaman

2014-03-01

304

Effect of silibinin on endothelial dysfunction and ADMA levels in obese diabetic mice  

PubMed Central

Background Cardiovascular diseases (CVD) in diabetic patients have endothelial dysfunction as a key pathogenetic event. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), plays a pivotal role in endothelial dysfunction. Different natural polyphenols have been shown to preserve endothelial function and prevent CVD. In this study, we assessed the effect of silibinin, a widely used flavonolignan from milk thistle, on ADMA levels and endothelial dysfunction in db/db mice. Methods Eight-week-old db/db mice were administrated a 20 mg/Kg i.p. daily dose of silibinin (n = 6) or vehicle (n = 6) for four weeks. Heterozygous lean db/m mice served as control. Plasma, aorta and liver ADMA levels were determined by ELISA. Vascular reactivity to phenilephrine (PE), acetylcholine (ACh), sodium nitroprusside (SNP) and ADMA was assessed in isolated aortic segments, in wire myograph. Results Plasma and aorta ADMA levels were higher in db/db than in control lean mice. Silibinin administration markedly decreased plasma ADMA; consistently, aorta ADMA was reduced in silibinin-treated animals. Plasma and aorta ADMA levels exhibited a positive correlation, whereas liver ADMA was inversely correlated with both plasma and aorta ADMA concentrations. Endothelium-(NO)-dependent vasodilatation to ACh was impaired in db/db mice and was restored in the silibinin group, in accordance with the observed reduction of plasma and vascular levels of ADMA. Endothelium-independent vasodilatation to SNP was not modified by silibinin administration; contractile tone induced in isolated aorta from db/db mice by challenging with exogenous ADMA was not affected by the treatment. Conclusions Silibinin markedly improves endothelial dysfunction in db/db mice by reducing circulating and vascular ADMA levels. Clinical studies are warranted to assess the efficacy of silibinin for cardiovascular protection. PMID:21756303

2011-01-01

305

Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice.  

PubMed

Different regimens of food restriction have been associated with protection against obesity, diabetes and CVD. In the present study, we hypothesised that food restriction would bring benefits to atherosclerosis- and diabetes-prone hypercholesterolaemic LDL-receptor knockout mice. For this purpose, 2-month-old mice were submitted to an intermittent fasting (IF) regimen (fasting every other day) over a 3-month period, which resulted in an overall 20 % reduction in food intake. Contrary to our expectation, epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively, in the IF mice compared with the ad libitum-fed mice. Accordingly, plasma levels of leptin were 50 % higher in the IF mice than in the ad libitum-fed mice. In addition, the IF mice showed increased plasma levels of total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). As expected, in wild-type mice, the IF regimen decreased plasma cholesterol levels and epididymal fat mass. Glucose homeostasis was also disturbed by the IF regimen in LDL-receptor knockout mice. Elevated levels of glycaemia (40 %), insulinaemia (50 %), glucose intolerance and insulin resistance were observed in the IF mice. Systemic inflammatory markers, TNF-? and C-reactive protein, were significantly increased and spontaneous atherosclerosis development were markedly increased (3-fold) in the IF mice. In conclusion, the IF regimen induced obesity and diabetes and worsened the development of spontaneous atherosclerosis in LDL-receptor knockout mice. Although being efficient in a wild-type background, this type of food restriction is not beneficial in the context of genetic hypercholesterolaemia. PMID:24176004

Dorighello, Gabriel G; Rovani, Juliana C; Luhman, Christopher J F; Paim, Bruno A; Raposo, Helena F; Vercesi, Anibal E; Oliveira, Helena C F

2014-03-28

306

Anti-diabetic effects of emodin involved in the activation of PPARgamma on high-fat diet-fed and low dose of streptozotocin-induced diabetic mice.  

PubMed

Rheum palmatum Linn has been widely applied in the clinical treatment of diabetes mellitus. It has been found that emodin as the major bioactive component of R. palmatum L exhibits the competency to activate peroxisomal proliferator-activated receptor-gamma (PPARgamma) in vitro. So the aim of this study was to evaluate the anti-diabetic effects of emodin through the activation of PPARgamma on high-fat diet-fed and low dose of streptozotocin (STZ)-induced diabetic mice. The diabetic mice were intraperitoneally injected with emodin for three weeks. No changes of food consumption and the body weight in emodin-treated mice were monitored daily during the entire experiment. At the end of experiment, the levels of blood glucose, triglyceride and total cholesterol in serum were significantly decreased after emodin treatment. However, serum high-density lipoprotein cholesterol (HDLc) concentration was significantly elevated. The glucose tolerance and insulin sensitivity in emodin-treated group were significantly improved. Furthermore, the results of quantitative RT-PCR analysis showed that emodin significantly elevated the mRNA expression level of PPARgamma and regulated the mRNA expressions of LPL, FAT/CD36, resistin and FABPs (ap2) in liver and adipocyte tissues. No effects on the mRNA expressions of PPARalpha and PPARalpha-target genes were observed. Taken together, the results suggested that the activation of PPARgamma and the modulation of metabolism-related genes were likely involved in the anti-diabetic effects of emodin. PMID:19699280

Xue, Jianfeng; Ding, Wenjun; Liu, Yan

2010-04-01

307

Reactivity of tracheal smooth muscles in albino rats with experimental diabetes mellitus treated with a new complex compound of oxovanadium (IV) and isonicotinic acid hydrazide.  

PubMed

We studied functional properties of tracheal smooth muscle cells in rats with diabetes mellitus. Reactivity of tracheal smooth muscles increased in rats with experimental alloxan-induced diabetes mellitus. A new complex compound of oxovanadium (IV) and isonicotinic acid hydrazide affected reactivity of tracheal smooth muscles in albino rats with experimental type I diabetes mellitus. This new organic vanadium-containing compound reduced contractility of tracheal smooth muscles in rats and potentiated relaxation of smooth muscle cells in the trachea in response to exogenous nitric oxide. PMID:12937677

Khafiz'yanova, R Kh; Minnebaev, M M; Gallyamov, R M; Latypov, R S; Gosmanov, A R; Aleeva, G N

2003-06-01

308

Supplementary effect by harvest period of Lentinus edodes on the levels of blood glucose and serum lipid in diabetic KK mice  

Technology Transfer Automated Retrieval System (TEKTRAN)

This study was carried out to investigate the effect of Lentinus edodes which were harvested at different times of maturity on blood glucose and lipid levels in diabetic mice. The diabetic KK mice were fed diet supplemented with Lentinus edodes harvested early (LE) or late (LL) for eight weeks, and ...

309

Podocyte-Specific GLUT4-Deficient Mice Have Fewer and Larger Podocytes and Are Protected From Diabetic Nephropathy  

PubMed Central

Podocytes are a major component of the glomerular filtration barrier, and their ability to sense insulin is essential to prevent proteinuria. Here we identify the insulin downstream effector GLUT4 as a key modulator of podocyte function in diabetic nephropathy (DN). Mice with a podocyte-specific deletion of GLUT4 (G4 KO) did not develop albuminuria despite having larger and fewer podocytes than wild-type (WT) mice. Glomeruli from G4 KO mice were protected from diabetes-induced hypertrophy, mesangial expansion, and albuminuria and failed to activate the mammalian target of rapamycin (mTOR) pathway. In order to investigate whether the protection observed in G4 KO mice was due to the failure to activate mTOR, we used three independent in vivo experiments. G4 KO mice did not develop lipopolysaccharide-induced albuminuria, which requires mTOR activation. On the contrary, G4 KO mice as well as WT mice treated with the mTOR inhibitor rapamycin developed worse adriamycin-induced nephropathy than WT mice, consistent with the fact that adriamycin toxicity is augmented by mTOR inhibition. In summary, GLUT4 deficiency in podocytes affects podocyte nutrient sensing, results in fewer and larger cells, and protects mice from the development of DN. This is the first evidence that podocyte hypertrophy concomitant with podocytopenia may be associated with protection from proteinuria. PMID:24101677

Guzman, Johanna; Jauregui, Alexandra N.; Merscher-Gomez, Sandra; Maiguel, Dony; Muresan, Cristina; Mitrofanova, Alla; Diez-Sampedro, Ana; Szust, Joel; Yoo, Tae-Hyun; Villarreal, Rodrigo; Pedigo, Christopher; Molano, R. Damaris; Johnson, Kevin; Kahn, Barbara; Hartleben, Bjoern; Huber, Tobias B.; Saha, Jharna; Burke, George W.; Abel, E. Dale; Brosius, Frank C.; Fornoni, Alessia

2014-01-01

310

Effect of Green Tea Extract/Poly-?-Glutamic Acid Complex in Obese Type 2 Diabetic Mice  

PubMed Central

Background The increasing prevalence of type 2 diabetes mellitus (T2DM) is associated with the rapid spread of obesity. Obesity induces insulin resistance, resulting in ?-cell dysfunction and thus T2DM. Green tea extract (GTE) has been known to prevent obesity and T2DM, but this effect is still being debated. Our previous results suggested that circulating green tea gallated catechins (GCs) hinders postprandial blood glucose lowering, regardless of reducing glucose and cholesterol absorption when GCs are present in the intestinal lumen. This study aimed to compare the effect of GTE with that of GTE coadministered with poly-?-glutamic acid (?-PGA), which is likely to inhibit the intestinal absorption of GCs. Methods The db/db mice and age-matched nondiabetic mice were provided with normal chow diet containing GTE (1%), ?-PGA (0.1%), or GTE+?-PGA (1%:0.1%) for 4 weeks. Results In nondiabetic mice, none of the drugs showed any effects after 4 weeks. In db/db mice, however, weight gain and body fat gain were significantly reduced in the GTE+?-PGA group compared to nondrug-treated db/db control mice without the corresponding changes in food intake and appetite. Glucose intolerance was also ameliorated in the GTE+?-PGA group. Histopathological analyses showed that GTE+?-PGA-treated db/db mice had a significantly reduced incidence of fatty liver and decreased pancreatic islet size. Neither GTE nor ?-PGA treatment showed any significant results. Conclusion These results suggest that GTE+?-PGA treatment than GTE or ?-PGA alone may be a useful tool for preventing both obesity and obesity-induced T2DM. PMID:23807923

Bae, Ki-Cheor; Park, Jae-Hyung; Na, Ann-Yae; Kim, Sun-Joo; Ahn, Shinbyoung; Kim, Sang-Pyo; Oh, Byung-Chul; Cho, Ho-Chan

2013-01-01

311

The H1-receptor antagonist cetirizine ameliorates high-fat diet-induced glucose intolerance in male C57BL/6 mice, but not diabetes outcome in female non-obese diabetic (NOD) mice.  

PubMed

Abstract Background. It has been proposed that the histamine 1-receptor (H1-receptor) not only promotes allergic reactions, but also modulates innate immunity and autoimmune reactions. In line with this, we have recently reported that the H1-receptor antagonist cetirizine partially counteracts cytokine-induced beta-cell signaling and destruction. Therefore, the aim of this study was to determine whether cetirizine affects diabetes in NOD mice, a model for human type 1 diabetes, and glucose intolerance in high-fat diet C57BL/6 mice, a model for human glucose intolerance. Methods. Female NOD mice were treated with cetirizine in the drinking water (25 mg/kg body weight) from 9 until 30 weeks of age during which precipitation of diabetes was followed. Male C57BL/6 mice were given a high-fat diet from 5 weeks of age. When the mice were 12 weeks of age cetirizine was given for 2 weeks in the drinking water. The effects of cetirizine were analyzed by blood glucose determinations, glucose tolerance tests, and insulin sensitivity tests. Results. Cetirizine did not affect diabetes development in NOD mice. On the other hand, cetirizine treatment for 1 week protected against high-fat diet-induced hyperglycemia. The glucose tolerance after 2 weeks of cetirizine treatment was improved in high-fat diet mice. We observed no effect of cetirizine on the insulin sensitivity of high-fat diet mice. Conclusion. Our results suggest a protective effect of cetirizine against high-fat diet-induced beta-cell dysfunction, but not against autoimmune beta-cell destruction. PMID:25291144

Anvari, Ebrahim; Wang, Xuan; Sandler, Stellan; Welsh, Nils

2014-10-01

312

Effect of Tumor Necrosis Factor o~ on Insulin-dependent Diabetes Mellitus in NOD Mice. I. The Early Development of Autoimmunity and the Diabetogenic Process  

Microsoft Academic Search

Summary Tumor necrosis factor (TNF) ot is a cytokine that has potent immune regulatory functions. To assess the potential role of this cytokine in the early development of autoimmunity, we investigated the effect of TNF on the development of insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice, a spontaneous murine model for autoimmune, insulin-dependent type I diabetes. Treatment of

Xiao-Dong Yang; Roland Tisch; Steven M. Singer; Zhu A. Cao; Roland S. Liblau; Robert D. Schreiber; Hugh O. McDevitt

313

Effect of Exercise on Kidney Function, Oxidative Stress, and Inflammation in Type 2 Diabetic KK-Ay Mice  

PubMed Central

Exercise is recommended for the management of type 2 diabetes, but its effects on diabetic nephropathy (DN) are still unknown. We hypothesized that appropriate exercise improves early DN via attenuation of inflammation and oxidative damage. Type 2 diabetic KK-Ay mice, a spontaneous DN model, underwent two different kinds of exercise (i.e., moderate and low intensity). Sedentary mice or those undergoing an exercise regimen causing no significant body weight loss were used. We examined the urinary excretion of albumin, number of podocytes and macrophages, renal expressions of HIF-1? and MCP-1, and biomarkers of oxidative stress such as urinary 8-OHdG and serum SOD. Exercise reduced urinary levels of albumin and also maintained the number of podocytes in the exercised KK-Ay mice independently of improvements of overweight and hyperglycemia, although moderate-intensity exercise increased expression of HIF-1?. Sedentary KK-Ay mice showed increased expression of MCP-1 and infiltration of macrophage, increased urinary 8-OhdG, and decreased serum SOD levels compared with exercised KK-Ay mice. On the whole, low-intensity exercise attenuates progression of early DN without affecting marked renal ischemia. Reduction rates of urinary albumin and maintained podocyte numbers, with parallel improvements in oxidative damage and inflammation, are related to beneficial effects of exercise in diabetic kidney disease. PMID:22899901

Ishikawa, Yuji; Gohda, Tomohito; Tanimoto, Mitsuo; Omote, Keisuke; Furukawa, Masako; Yamaguchi, Saori; Murakoshi, Maki; Hagiwara, Shinji; Horikoshi, Satoshi; Funabiki, Kazuhiko; Tomino, Yasuhiko

2012-01-01

314

Importance of sulfur-containing metabolites in discriminating fecal extracts between normal and type-2 diabetic mice.  

PubMed

A metabolic disorder such as Type-2 Diabetes mellitus (T2DM) is a complex disease induced by genetic, environmental, and nutritional factors. The db/db mouse model, bearing a nonfunctional leptin receptor, is widely used to investigate the pathophysiology of T2DM. Fecal extracts of db/db and wild-type littermates were studied to unravel a broad spectrum of new and relevant metabolites related to T2DM as proxies of the interplay of gut microbiome and murine metabolomes. The nontargeted metabolomics approach consists of an integrated analytical concept of high-resolution mass spectrometry FT-ICR-MS, followed by UPLC-TOF-MS/MS experiments. We demonstrate that a metabolic disorder such as T2DM affects the gastrointestinal tract environment, thereby influencing different metabolic pathways and their respective metabolites in diabetic mice. Fatty acids, bile acids concerning cholic and deoxycholic acid, and steroid metabolism were highly discriminative comparing fecal meta-metabolomes of wt and db/db mice. Furthermore, sulfur-(S)-containing metabolites including N-acyl taurines were altered in diabetic mice, enabling us to focus on S-containing metabolites, especially the sulfate and taurine conjugates of bile and fatty acids. Different sulfate containing bile acids including sulfocholic acid, oxocholic acid sulfate, taurocholic acid sulfate, and cyprinol sulfate were significantly altered in diabetic mice. Moreover, we identified 12 new sulfate and taurine conjugates of hydroxylated fatty acids with significant importance in T2DM metabolism in db/db mice. PMID:24991707

Walker, Alesia; Lucio, Marianna; Pfitzner, Barbara; Scheerer, Markus F; Neschen, Susanne; de Angelis, Martin Hrab?; Hartmann, Anton; Schmitt-Kopplin, Philippe

2014-10-01

315

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

PubMed

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. PMID:17268057

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

2007-02-01

316

Improvement of antioxidant balance in diabetes mellitus type 1 mice by glutathione supplement.  

PubMed

Diabetes mellitus (DM) type 1 is a chronic disease characterized by hyperglycemia and lacking of insulin. Oxidative stress participates in development and progression of DM, in which changes of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) content were noted in DM mice. In this study, the effects of GSH supplement on anti-oxidation system in streptozotocin-induced DM type 1 Imprinting Control Region (ICR) mice were determined. The co-treatment of insulin and GSH significantly lowered the hepatic manganese superoxide dismutase (Mn-SOD), CAT, and GPx mRNA expression. Moreover, co-administration of insulin and GSH restored SOD and CAT activities to non-DM group except that of the CAT activity in the kidney. The GSH contents and GSH/GSSG ratio in the mouse livers were normalized to the normal levels by the GSH treatment and the co-administration of insulin and GSH. These observations reveal that GSH supplement potentially has the protective roles in delaying diabetic progression via the improvement of antioxidant balance. PMID:25362599

Pimson, Charinya; Chatuphonprasert, Waranya; Jarukamjorn, Kanokwan

2014-11-01

317

Effects of in vivo antioxidant enzyme activities of myrtle oil in normoglycaemic and alloxan diabetic rabbits.  

PubMed

In this study we aimed to evaluate the in vivo effects of myrtle oil (myrtii oleum) on the antioxidant enzymes such as superoxide dismutase and catalase, the levels of malondialdehyde in liver tissues as an index of lipid peroxidation and nitrite-nitrate levels in normoglycaemic and alloxan-induced diabetic and MO-treated rabbits. In our previous study, we assumed that MO with a dose of 50 mg/kg, possesses a hypoglycemic activity and this activity was independent from the effects of insulin. Myrtle oil exerts its hypoglycemic activity by enhanced glycolysis, glycogenesis and decreased glycogenolysis. What is more glucose load data strongly suggest that MO treatment produces hypoglycemia mainly by reducing intestinal absorption of glucose, so MO could be an alpha-glycosidase enzyme inhibitor which had a hypoglycaemic effect only on alloxan-induced diabetic rabbits on the fourth hour and on orally glucose loaded group. The major finding of this new study is that, MO may not offer any protection against oxidative stress during acute studies in normoglycemic and diabetic groups. Although the levels of superoxide dismutase and catalase enzyme activities did not change during acute studies in diabetes + MO group, there was a significant change at the end of 21 days. There is a very limited knowledge about MO and its effects on diabetes. Therefore, we tried to explain the mechanism that might underlie the protective effects of MO with this paper. PMID:17101252

Sepici-Dincel, Aylin; Açikgöz, Sereften; Cevik, Cemal; Sengelen, Meltem; Ye?ilada, Erdem

2007-04-01

318

BBT improves glucose homeostasis by ameliorating ?-cell dysfunction in type 2 diabetic mice.  

PubMed

Impaired glucose-stimulated insulin secretion (GSIS) and increasing ?-cell death are two typical dysfunctions of pancreatic ?-cells in individuals that are destined to develop type 2 diabetes, and improvement of ?-cell function through GSIS enhancement and/or inhibition of ?-cell death is a promising strategy for anti-diabetic therapy. In this study, we discovered that the small molecule, N-(2-benzoylphenyl)-5-bromo-2-thiophenecarboxamide (BBT), was effective in both potentiating GSIS and protecting ?-cells from cytokine- or streptozotocin (STZ)-induced cell death. Results of further studies revealed that cAMP/PKA and long-lasting (L-type) voltage-dependent Ca(2) (+) channel/CaMK2 pathways were involved in the action of BBT against GSIS, and that the cAMP/PKA pathway was essential for the protective action of BBT on ?-cells. An assay using the model of type 2 diabetic mice induced by high-fat diet combined with STZ (STZ/HFD) demonstrated that BBT administration efficiently restored ?-cell functions as indicated by the increased plasma insulin level and decrease in the ?-cell loss induced by STZ/HFD. Moreover, the results indicated that BBT treatment decreased fasting blood glucose and HbA1c and improved oral glucose tolerance further highlighting the potential of BBT in anti-hyperglycemia research. PMID:25572265

Yao, Xin-Gang; Xu, Xin; Wang, Gai-Hong; Lei, Min; Quan, Ling-Ling; Cheng, Yan-Hua; Wan, Ping; Zhou, Jin-Pei; Chen, Jing; Hu, Li-Hong; Shen, Xu

2015-03-01

319

Transplantation of betacellulin-transduced islets improves glucose intolerance in diabetic mice  

PubMed Central

Type 1 diabetes is an autoimmune disease caused by permanent destruction of insulin-producing pancreatic ? cells and requires lifelong exogenous insulin therapy. Recently, islet transplantation has been developed, and although there have been significant advances, this approach is not widely used clinically due to the poor survival rate of the engrafted islets. We hypothesized that improving survival of engrafted islets through ex vivo genetic engineering could be a novel strategy for successful islet transplantation. We transduced islets with adenoviruses expressing betacellulin, an epidermal growth factor receptor ligand, which promotes ?-cell growth and differentiation, and transplanted these islets under the renal capsule of streptozotocin-induced diabetic mice. Transplantation with betacellulin-transduced islets resulted in prolonged normoglycemia and improved glucose tolerance compared with those of control virus-transduced islets. In addition, increased microvascular density was evident in the implanted islets, concomitant with increased endothelial von Willebrand factor immunoreactivity. Finally, cultured islets transduced with betacellulin displayed increased proliferation, reduced apoptosis and enhanced glucose-stimulated insulin secretion in the presence of cytokines. These experiments suggest that transplantation with betacellulin-transduced islets extends islet survival and preserves functional islet mass, leading to a therapeutic benefit in type 1 diabetes. PMID:24875130

Song, Mi-Young; Bae, Ui-Jin; Jang, Kyu Yun; Park, Byung-Hyun

2014-01-01

320

Modulations of cytochrome P450 expression in diabetic mice by berberine.  

PubMed

Berberine, an isoquinoline alkaloid isolated from medicinal plants such as Berberis aristata, Coptis chinesis, Coptis japonica, Coscinium fenestatun, and Hydrastis Canadensis, is widely used in Asian countries for the treatment of diabetes, hypertension, and hypercholesterolemia. Interaction between berberine and the cytochrome P450 enzymes (CYPs) has been extensively reported, but there are only a few reports of this interaction in the diabetic state. In this study, the effect of berberine on the mRNA of the CYPs in primary mouse hepatocytes and in streptozotocin (STZ)-induced diabetic mice was investigated. In primary mouse hepatocytes, berberine suppressed the induction of Cyp1a1, Cyp1a2, Cyp2e1, Cyp3a11, Cyp4a10, and Cyp4a14 mRNA expression by their prototypical inducers in a concentration-dependent fashion. However, berberine treatment alone increased the expression of Cyp2b9 and Cyp2b10 mRNA. In vivo, berberine showed the same hypoglycemic activity as metformin, an established hypoglycemic drug. The hepatic mRNA levels of Cyp1a1, Cyp2b9, Cyp2b10, Cyp3a11, Cyp4a10, and Cyp4a14 were increased in STZ-induced diabetic mice. Interestingly, berberine itself suppressed the expression of Cyp2e1, an adverse hepatic event-associated enzyme, while the expression of Cyp3a11, Cyp4a10, and Cyp4a14 were restored to normal levels by berberine. In conclusion, berberine has the potential to modify the expression of CYPs by either suppression or enhancement of CYPs' levels. Consumption of berberine as an anti-hyperglycemic compound by diabetic patients might provide an extra benefit due to its potential to restore the expression of Cyp2e1, Cyp3a, and Cyp4a to normal levels. However, an herb-drug interaction might be of concern since any berberine-containing product would definitely cause pronounced interactions based on CYP3A4 inhibition. PMID:22342832

Chatuphonprasert, Waranya; Nemoto, Nobuo; Sakuma, Tsutomu; Jarukamjorn, Kanokwan

2012-03-01

321

Lentivectors encoding immunosuppressive proteins genetically engineer pancreatic beta-cells to correct diabetes in allogeneic mice.  

PubMed

The effectiveness of genetic engineering with lentivectors to protect transplanted cells from allogeneic rejection was examined using, as a model, type 1 diabetes treatment with beta-cell transplantation, whose widespread use has been limited by the requirement for sustained immunosuppressive treatment to prevent graft rejection. We examined whether lentivectors expressing select immunosuppressive proteins encoded by the adenoviral genome early region 3 (AdE3) would protect transplanted beta-cells from an alloimmune attack. The insulin-producing beta-cell line beta TC-tet (C3HeB/FeJ-derived) was transduced with lentiviruses encoding the AdE3 proteins gp19K and RID alpha/beta. The efficiency of lentiviral transduction of beta TC-tet cells exceeded 85%. Lentivector expression of gp19K decreased surface class I major histocompatibility complex expression by over 90%, whereas RID alpha/beta expression inhibited cytokine-induced Fas upregulation by over 75%. beta TC-tet cells transduced with gp19K and RID alpha/beta lentivectors, but not with a control lentivector, provided prolonged correction of hyperglycemia after transplantation into diabetic BALB/c severe combined immunodeficient mice reconstituted with allogeneic immune effector cells or into diabetic allogeneic BALB/c mice. Thus, genetic engineering of beta-cells using gp19K- and RID alpha/beta-expressing lentiviral vectors may provide an alternative that has the potential to eliminate or reduce treatment with the potent immunosuppressive agents necessary at present for prolonged engraftment with transplanted islets. PMID:19112449

Kojaoghlanian, T; Joseph, A; Follenzi, A; Zheng, J H; Leiser, M; Fleischer, N; Horwitz, M S; DiLorenzo, T P; Goldstein, H

2009-03-01

322

Quantitative Proteomic and Functional Analysis of Liver Mitochondria from High Fat Diet (HFD) Diabetic Mice*  

PubMed Central

Insulin resistance plays a major role in the development of type 2 diabetes and obesity and affects a number of biological processes such as mitochondrial biogenesis. Though mitochondrial dysfunction has been linked to the development of insulin resistance and pathogenesis of type 2 diabetes, the precise mechanism linking the two is not well understood. We used high fat diet (HFD)-induced obesity dependent diabetes mouse models to gain insight into the potential pathways altered with metabolic disease, and carried out quantitative proteomic analysis of liver mitochondria. As previously reported, proteins involved in fatty acid oxidation, branched chain amino acid degradation, tricarboxylic acid cycle, and oxidative phosphorylation were uniformly up-regulated in the liver of HFD fed mice compared with that of normal diet. Further, our studies revealed that retinol metabolism is distinctly down-regulated and the mitochondrial structural proteins—components of mitochondrial inter-membrane space bridging (MIB) complex (Mitofilin, Sam50, and ChChd3), and Tim proteins—essential for protein import, are significantly up-regulated in HFD fed mice. Structural and functional studies on HFD and normal diet liver mitochondria revealed remodeling of HFD mitochondria to a more condensed form with increased respiratory capacity and higher ATP levels compared with normal diet mitochondria. Thus, it is likely that the structural remodeling is essential to accommodate the increased protein content in presence of HFD: the mechanism could be through the MIB complex promoting contact site and crista junction formation and in turn facilitating the lipid and protein uptake. PMID:24030101

Guo, Yurong; Darshi, Manjula; Ma, Yuliang; Perkins, Guy A.; Shen, Zhouxin; Haushalter, Kristofer J.; Saito, Rintaro; Chen, Ai; Lee, Yun Sok; Patel, Hemal H.; Briggs, Steven P.; Ellisman, Mark H.; Olefsky, Jerrold M.; Taylor, Susan S.

2013-01-01

323

Differential proteomic analysis of the pancreas of diabetic db/db mice reveals the proteins involved in the development of complications of diabetes mellitus.  

PubMed

Type 2 diabetes mellitus is characterized by hyperglycemia and insulin-resistance. Diabetes results from pancreatic inability to secrete the insulin needed to overcome this resistance. We analyzed the protein profile from the pancreas of ten-week old diabetic db/db and wild type mice through proteomics. Pancreatic proteins were separated in two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and significant changes in db/db mice respect to wild type mice were observed in 27 proteins. Twenty five proteins were identified by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) and their interactions were analyzed using search tool for the retrieval of interacting genes/proteins (STRING) and database for annotation, visualization and integrated discovery (DAVID). Some of these proteins were Pancreatic ?-amylase, Cytochrome b5, Lithostathine-1, Lithostathine-2, Chymotrypsinogen B, Peroxiredoxin-4, Aspartyl aminopeptidase, Endoplasmin, and others, which are involved in the metabolism of carbohydrates and proteins, as well as in oxidative stress, and inflammation. Remarkably, these are mostly endoplasmic reticulum proteins related to peptidase activity, i.e., they are involved in proteolysis, glucose catabolism and in the tumor necrosis factor-mediated signaling pathway. These results suggest mechanisms for insulin resistance, and the chronic inflammatory state observed in diabetes. PMID:24886809

Pérez-Vázquez, Victoriano; Guzmán-Flores, Juan M; Mares-Álvarez, Daniela; Hernández-Ortiz, Magdalena; Macías-Cervantes, Maciste H; Ramírez-Emiliano, Joel; Encarnación-Guevara, Sergio

2014-01-01

324

Differential Proteomic Analysis of the Pancreas of Diabetic db/db Mice Reveals the Proteins Involved in the Development of Complications of Diabetes Mellitus  

PubMed Central

Type 2 diabetes mellitus is characterized by hyperglycemia and insulin-resistance. Diabetes results from pancreatic inability to secrete the insulin needed to overcome this resistance. We analyzed the protein profile from the pancreas of ten-week old diabetic db/db and wild type mice through proteomics. Pancreatic proteins were separated in two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and significant changes in db/db mice respect to wild type mice were observed in 27 proteins. Twenty five proteins were identified by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) and their interactions were analyzed using search tool for the retrieval of interacting genes/proteins (STRING) and database for annotation, visualization and integrated discovery (DAVID). Some of these proteins were Pancreatic ?-amylase, Cytochrome b5, Lithostathine-1, Lithostathine-2, Chymotrypsinogen B, Peroxiredoxin-4, Aspartyl aminopeptidase, Endoplasmin, and others, which are involved in the metabolism of carbohydrates and proteins, as well as in oxidative stress, and inflammation. Remarkably, these are mostly endoplasmic reticulum proteins related to peptidase activity, i.e., they are involved in proteolysis, glucose catabolism and in the tumor necrosis factor-mediated signaling pathway. These results suggest mechanisms for insulin resistance, and the chronic inflammatory state observed in diabetes. PMID:24886809

Pérez-Vázquez, Victoriano; Guzmán-Flores, Juan M.; Mares-Álvarez, Daniela; Hernández-Ortiz, Magdalena; Macías-Cervantes, Maciste H.; Ramírez-Emiliano, Joel; Encarnación-Guevara, Sergio

2014-01-01

325

Chronic Ingestion of Advanced Glycation End Products Induces Degenerative Spinal Changes and Hypertrophy in Aging Pre-Diabetic Mice  

PubMed Central

Intervertebral disc (IVD) degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs), cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG)) on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+) or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG). dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions. PMID:25668621

Illien-Jünger, Svenja; Lu, Young; Qureshi, Sheeraz A.; Hecht, Andrew C.; Cai, Weijing; Vlassara, Helen; Striker, Gary E.; Iatridis, James C.

2015-01-01

326

Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice by reducing brain ?-amyloid through PPAR? activation  

PubMed Central

Aim: To examine the effects of pioglitazone, a PPAR? agonist, on memory performance and brain amyloidogenesis in streptozotocin (STZ)-induced diabetic mice. Methods: ICR male mice were injected with STZ (150 mg/kg, iv) to induce experimental diabetes. Pioglitazone (9 and 18 mg·kg-1·d-1, po) was administered for 6 weeks. Passive avoidance and Morris water maze (MWM) tests were used to evaluate cognitive function. The blood glucose and serum insulin levels were detected using the glucose oxidase method and an ELISA assay, respectively. ?-amyloid (A?), ?-amyloid precursor protein (APP), ?-amyloid precursor protein cleaving enzyme 1 (BACE1), NF-?B p65, the receptor for advanced glycation end products (RAGE) and PPAR? in the brains were analyzed using Western blotting assays. Results: The STZ-induced diabetic mice characterized by hyperglycemia and hypoinsulinemia performed poorly in both the passive avoidance and MWM tests, accompanied by increased A?1–40/A?1–42, APP, BACE1, NF-?B p65 and RAGE levels and decreased PPAR? level in the hippocampus and cortex. Chronic pioglitazone treatment significantly ameliorated the memory deficits and amyloidogenesis of STZ-induced diabetic mice, and suppressed expression of APP, BACE1, RAGE and NF-?B p65, and activated PPAR? in the hippocampus and cortex. However, pioglitazone did not significantly affect blood glucose and insulin levels. Conclusion: Pioglitazone ameliorates memory deficits in STZ-induced diabetic mice by reducing brain A? level via activation of PPAR?, which is independent of its effects on blood glucose and insulin levels. The results suggest that pioglitazone may be used for treating the cognitive dysfunction in type 1 diabetes mellitus. PMID:23524568

Liu, Li-ping; Yan, Tian-hua; Jiang, Li-ying; Hu, Wei; Hu, Meng; Wang, Chao; Zhang, Qian; Long, Yan; Wang, Jiang-qing; Li, Yong-qi; Hu, Mei; Hong, Hao

2013-01-01

327

Anti-diabetic effect of purple corn extract on C57BL/KsJ db/db mice  

PubMed Central

BACKGROUND/OBJECTIVES Recently, anthocyanins have been reported to have various biological activities. Furthermore, anthocyanin-rich purple corn extract (PCE) ameliorated insulin resistance and reduced diabetes-associated mesanginal fibrosis and inflammation, suggesting that it may have benefits for the prevention of diabetes and diabetes complications. In this study, we determined the anthocyanins and non-anthocyanin component of PCE by HPLC-ESI-MS and investigated its anti-diabetic activity and mechanisms using C57BL/KsJ db/db mice. MATERIALS/METHODS The db/db mice were divided into four groups: diabetic control group (DC), 10 or 50 mg/kg PCE (PCE 10 or PCE 50), or 10 mg/kg pinitol (pinitol 10) and treated with drugs once per day for 8 weeks. During the experiment, body weight and blood glucose levels were measured every week. At the end of treatment, we measured several diabetic parameters. RESULTS Compared to the DC group, Fasting blood glucose levels were 68% lower in PCE 50 group and 51% lower in the pinitol 10 group. Furthermore, the PCE 50 group showed 2- fold increased C-peptide and adiponectin levels and 20% decreased HbA1c levels, than in the DC group. In pancreatic islets morphology, the PCE- or pinitol-treated mice showed significant prevention of pancreatic ?-cell damage and higher insulin content. Microarray analyses results indicating that gene and protein expressions associated with glycolysis and fatty acid metabolism in liver and fat tissues. In addition, purple corn extract increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6pase) genes in liver, and also increased glucose transporter 4 (GLUT4) expressions in skeletal muscle. CONCLUSIONS Our results suggested that PCE exerted anti-diabetic effects through protection of pancreatic ?-cells, increase of insulin secretion and AMPK activation in the liver of C57BL/KsJ db/db mice. PMID:25671064

Huang, Bo; Wang, Zhiqiang; Park, Jong Hyuk; Ryu, Ok Hyun; Choi, Moon Ki; Lee, Jae-Yong; Kang, Young-Hee

2015-01-01

328

Changes in Liver Cell DNA Methylation Status in Diabetic Mice Affect Its FT-IR Characteristics  

PubMed Central

Background Lower levels of cytosine methylation have been found in the liver cell DNA from non-obese diabetic (NOD) mice under hyperglycemic conditions. Because the Fourier transform-infrared (FT-IR) profiles of dry DNA samples are differently affected by DNA base composition, single-stranded form and histone binding, it is expected that the methylation status in the DNA could also affect its FT-IR profile. Methodology/Principal Findings The DNA FT-IR signatures obtained from the liver cell nuclei of hyperglycemic and normoglycemic NOD mice of the same age were compared. Dried DNA samples were examined in an IR microspectroscope equipped with an all-reflecting objective (ARO) and adequate software. Conclusions/Significance Changes in DNA cytosine methylation levels induced by hyperglycemia in mouse liver cells produced changes in the respective DNA FT-IR profiles, revealing modifications to the vibrational intensities and frequencies of several chemical markers, including ?as –CH3 stretching vibrations in the 5-methylcytosine methyl group. A smaller band area reflecting lower energy absorbed in the DNA was found in the hyperglycemic mice and assumed to be related to the lower levels of –CH3 groups. Other spectral differences were found at 1700–1500 cm?1 and in the fingerprint region, and a slight change in the DNA conformation at the lower DNA methylation levels was suggested for the hyperglycemic mice. The changes that affect cytosine methylation levels certainly affect the DNA-protein interactions and, consequently, gene expression in liver cells from the hyperglycemic NOD mice. PMID:25019512

Vidal, Benedicto de Campos; Ghiraldini, Flávia Gerelli; Mello, Maria Luiza S.

2014-01-01

329

High-hydroxypropylated tapioca starch improves insulin resistance in genetically diabetic KKAy mice.  

PubMed

The hypoglycemic and antidiabetic effect of hydroxypropyl tapioca starch (HPTS) with a varying degree of substitution (DS: 0.058, 0.091, and 0.180) was investigated in rats and KKAy mice, an animal model of type 2 diabetes. The positive incremental area under the curve (IAUC) for glucose significantly decreased as the DS of HPTS increased. The IAUC after intragastric intubation of the highest HPTS (HPTS-III, DS = 0.180) was 55% of the IAUC of tapioca starch (TS). After 28 d, fasting blood glucose and insulin concentrations were significantly lower in rats fed HPTS-III (50 g/kg diet) than in those fed TS (P < 0.05). In KKAy mice fed HPTS-III (50 or 100 g/kg diet) for 33 d, as compared with TS, there was a delay in the detection of glucose in urine and also a decreased incidence of finding glucose in urine on days 7, 21, and 28; in addition, the AUCs for glucose in the oral glucose tolerance test on days 14 and 28 were significantly lower (P < 0.05 and P < 0.05, respectively). The plasma adiponectin concentration and the quantitative insulin sensitivity check index (QUICKI) were significantly higher in mice fed HPTS-III than in those fed TS (P < 0.01), whereas the homeostasis model assessment of insulin resistance (HOMA-IR) was lower (P < 0.01). Energy intake was significantly lower in mice fed HPTS-III than in those fed TS. These findings show that HPTS with a high DS resists digestion by alpha-amylase and improves insulin resistance in KKAy mice by decreasing energy intake. However, the potential mechanism by which HPTS-III decreases energy intake is unclear at present. PMID:19397723

Kato, R; Tachibe, M; Sugano, S; Kishida, T; Ebihara, K

2009-04-01

330

Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice  

SciTech Connect

AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK ? subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within ? subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome.

Li, Yuan-Yuan; Yu, Li-Fang; Zhang, Li-Na; Qiu, Bei-Ying; Su, Ming-Bo; Wu, Fang; Chen, Da-Kai; Pang, Tao; Gu, Min; Zhang, Wei; Ma, Wei-Ping; Jiang, Hao-Wen; Li, Jing-Ya, E-mail: jyli@mail.shcnc.ac.cn; Nan, Fa-Jun, E-mail: fjnan@mail.shcnc.ac.cn; Li, Jia, E-mail: jli@mail.shcnc.ac.cn

2013-12-01

331

Type 1 diabetes in NOD mice unaffected by mast cell deficiency.  

PubMed

Mast cells have been invoked as important players in immune responses associated with autoimmune diseases. Based on in vitro studies, or in vivo through the use of Kit mutant mice, mast cells have been suggested to play immunological roles in direct antigen presentation to both CD4(+) and CD8(+) T cells, in the regulation of T-cell and dendritic cell migration to lymph nodes, and in Th1 versus Th2 polarization, all of which could significantly impact the immune response against self-antigens in autoimmune disease, including type 1 diabetes (T1D). Until now, the role of mast cells in the onset and incidence of T1D has only been indirectly tested through the use of low-specificity mast cell inhibitors and activators, and published studies reported contrasting results. Our three laboratories have generated independently two strains of mast cell-deficient nonobese diabetic (NOD) mice, NOD.Cpa3(Cre/+) (Heidelberg) and NOD.Kit(W-sh/W-sh) (Leuven and Boston), to address the effects of mast cell deficiency on the development of T1D in the NOD strain. Our collective data demonstrate that both incidence and progression of T1D in NOD mice are independent of mast cells. Moreover, analysis of pancreatic lymph node cells indicated that lack of mast cells has no discernible effect on the autoimmune response, which involves both innate and adaptive immune components. Our results demonstrate that mast cells are not involved in T1D in the NOD strain, making their role in this process nonessential and excluding them as potential therapeutic targets. PMID:24917576

Gutierrez, Dario A; Fu, Wenxian; Schonefeldt, Susann; Feyerabend, Thorsten B; Ortiz-Lopez, Adriana; Lampi, Yulia; Liston, Adrian; Mathis, Diane; Rodewald, Hans-Reimer

2014-11-01

332

Differential gene expression in Lin-/VEGF-R2+ bone marrow-derived endothelial progenitor cells isolated from diabetic mice  

PubMed Central

Background Diabetes is known to impair the number and function of endothelial progenitor cells in the circulation, causing structural and functional alterations in the micro- and macro-vasculature. The aim of this study was to identify early diabetes-related changes in the expression of genes that have been reported to be closely involved in endothelial progenitor cell migration and function. Methods Based on review of current literature, this study examined the expression level of 35 genes that are known to be involved in endothelial progenitor cell migration and function in magnetically sorted Lin-/VEGF-R2+ endothelial progenitor cells obtained from the bone marrow of Akita mice in the early stages of diabetes (18 weeks) using RT-PCR and Western blotting. We used the Shapiro-Wilk and D’Agostino & Pearson Omnibus tests to assess normality. Differences between groups were evaluated by Student’s t-test for normally distributed data (including Welch correction in cases of unequal variances) or Mann–Whitney test for not normally distributed data. Results We observed a significant increase in the number of Lin-/VEGF-R2+ endothelial progenitor cells within the bone marrow in diabetic mice compared with non-diabetic mice. Two genes, SDF-1 and SELE, were significantly differentially expressed in diabetic Lin-/VEGF-R2+ endothelial progenitor cells and six other genes, CAV1, eNOS, CLDN5, NANOG, OCLN and BDNF, showed very low levels of expression in diabetic Lin-/VEGF-R2+ progenitor cells. Conclusion Low SDF-1 expression may contribute to the dysfunctional mobilization of bone marrow Lin-/VEGF-R2+ endothelial progenitor cells, which may contribute to microvascular injury in early diabetes. PMID:24521356

2014-01-01

333

STREPTOZOTOCIN-INDUCED DIABETES PARTIALLY ATTENUATES THE EFFECTS OF A HIGH-FAT DIET ON LIVER AND BRAIN FATTY ACID COMPOSITION IN MICE  

PubMed Central

The current study addresses the effects of a high-fat diet on liver and brain fatty acid compositions and the interaction of that diet with diabetes in a type 1 mouse model. Adult, male, normal and streptozotocin-induced diabetic C57BL/6 mice were fed standard (14% kcals from fat) or high-fat (54% kcals from fat, hydrogenated vegetable shortening and corn oil) diets for 8 weeks. Liver and whole brain total phospholipid fatty acid compositions were then determined by TLC/GC. In the liver of non-diabetic mice, the high-fat diet increased the percentages of 18:1n-9, 20:4n-6, and 22:5n-6 and decreased 18:2n-6 and 22:6n-3. Diabetes increased 16:0 in liver, and decreased 18:1n-7 and 20:4n-6. The effects of the high-fat diet on liver phospholipids in diabetic mice were similar to those in non-diabetic mice, or were of smaller magnitude. In the brain, the high-fat diet increased 18:0 and 20:4n-6 of non-diabetic, but not diabetic mice. Brain 22:5n-6 acid was increased by the high-fat diet in both non-diabetic and diabetic mice, but this increase was smaller in diabetic mice. Diabetes alone did not alter the percentage of any individual fatty acid in brain. This indicates that the effects of a high-fat diet on liver and brain phospholipid fatty acid compositions are mitigated by concomitant hyperglycemia with hypoinsulinemia. PMID:23893338

Levant, Beth; Ozias, Marlies K.; Guilford, Brianne L.; Wright, Douglas E.

2013-01-01

334

Transcriptome analysis of epigenetically modulated genome indicates signature genes in manifestation of type 1 diabetes and its prevention in NOD mice.  

PubMed

Classic genetic studies implicated several genes including immune response genes in the risk of developing type 1 diabetes in humans. However, recent evidence including discordant diabetes incidence among monozygotic twins suggested a role for epigenetics in disease manifestation. NOD mice spontaneously develop type 1 diabetes like humans and serve as an excellent model system to study the mechanisms of type 1 diabetes as well as the efficacy of maneuvers to manipulate the disease. Using this preclinical model, we have recently demonstrated that pharmacological inhibition of histone deacetylases can lead to histone hyperacetylation, selective up-regulation of interferon-? and its transactivator Tbx21/Tbet, and amelioration of autoimmune diabetes. In the current study, we show that chromatin remodeling can render splenocytes incapable of transferring diabetes into immunodeficient NOD.scid mice. To elucidate the underlying mechanisms of drug-mediated protection against type 1 diabetes, we performed global gene expression profiling of splenocytes using high throughput microarray technology. This unbiased transcriptome analysis unraveled the exaggerated expression of a novel set of closely related inflammatory genes in splenocytes of acutely diabetic mice and their repression in mice cured of diabetes by chromatin remodeling. Analysis of gene expression by qRT-PCR using RNA derived from spleens and pancreata of cured mice validated the suppression of most of these genes, indicating an inverse correlation between the high levels of these inflammatory genes and protection against diabetes in NOD mice. In addition, higher-level expression of genes involved in insulin sensitivity, erythropoiesis, hemangioblast generation, and cellular redox control was evident in spleens of cured mice, indicating their possible contribution to protection against type 1 diabetes. Taken together, these results are consistent with the involvement of epistatic mechanisms in the manifestation of autoimmune diabetes and further indicate the utility of chromatin remodeling in curing this complex autoimmune disorder. PMID:23383062

Jayaraman, Sundararajan; Patel, Akshay; Jayaraman, Arathi; Patel, Vasu; Holterman, Mark; Prabhakar, Bellur

2013-01-01

335

Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice.  

PubMed

We have reported that exercise capacity is reduced in high fat diet (HFD)-induced diabetic mice, and that this reduction is associated with impaired mitochondrial function in skeletal muscle (SKM). However, it remains to be clarified whether the treatment of diabetes ameliorates the reduced exercise capacity. Therefore, we examined whether an insulin-sensitizing drug, pioglitazone, could improve exercise capacity in HFD mice. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated with or without pioglitazone (3 mg/kg/day) to yield the following 4 groups: ND+vehicle, ND+pioglitazone, HFD+vehicle, and HFD+pioglitazone (n=10 each). After 8 weeks, body weight, plasma glucose, and insulin in the HFD+vehicle were significantly increased compared to the ND+vehicle group. Pioglitazone normalized the insulin levels in HFD-fed mice, but did not affect the body weight or plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in the HFD+vehicle, and this reduction was almost completely ameliorated in HFD+pioglitazone mice. ADP-dependent mitochondrial respiration, complex I and III activities, and citrate synthase activity were significantly decreased in the SKM of the HFD+vehicle animals, and these decreases were also attenuated by pioglitazone. NAD(P)H oxidase activity was significantly increased in the HFD+vehicle compared with the ND+vehicle, and this increase was ameliorated in HFD+pioglitazone mice. Pioglitazone improved the exercise capacity in diabetic mice, which was due to the improvement in mitochondrial function and attenuation of oxidative stress in the SKM. Our data suggest that pioglitazone may be useful as an agent for the treatment of diabetes mellitus. PMID:24964389

Takada, Shingo; Hirabayashi, Kagami; Kinugawa, Shintaro; Yokota, Takashi; Matsushima, Shouji; Suga, Tadashi; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Mizushima, Wataru; Masaki, Yoshihiro; Furihata, Takaaki; Katsuyama, Ryoichi; Okita, Koichi; Tsutsui, Hiroyuki

2014-10-01

336

Effect of Cnidoscolus aconitifolius leaf extract on the blood glucose and insulin levels of inbred type 2 diabetic mice.  

PubMed

The effects of Cnidoscolus aconitifolius (CA) leaf extract and chlorpropamide on blood glucose and insulin levels in the inbred type 2 diabetic mice are reported. After treatment with CA, the glucose levels were measured at 0 and 2-hour intervals in experimental groups and controls. Group I received no treatment and served as control; Group II was the reference and it received chlorpropamide; Groups I-III were moderately diabetic, 100-300 mg/dL blood glucose levels while Group IV were severely diabetic (> 300 mg/dL). Groups III and IV received CA and served as test groups. There was no significant difference between the blood glucose levels at 0 and 2 hours for the control group, (P>0.23) but there were statistically significant differences for Group II (P<0.0002); Group III (P<0.002) and Group IV (P<0.0001). For moderately diabetic mice, CA and chlorpropamide decreased the glucose levels by 25.6% and 16.3% respectively while for the severely diabetic mice CA decreased the blood glucose by 43.7%. It is proposed that CA has an insulinogenic property that possibly stimulated dormant beta-cells to secrete insulin. The histopathology of several organs in the treated animals was found to differ from the expected. The islets of Langerhans for example were found to be preserved in the time frame examined. Also the liver and kidney were found to display milder pathology in the treated groups. PMID:17531147

Oladeinde, F O; Kinyua, A M; Laditan, A A; Michelin, R; Bryant, J L; Denaro, F; Makinde, J M; Williams, A L; Kennedy, A P; Bronner, Y

2007-01-01

337

Regulator of Calcineurin 1 Isoform 4 (RCAN1.4) Is Overexpressed in the Glomeruli of Diabetic Mice  

PubMed Central

Calcineurin (CaN) is activated in diabetes and plays a role in glomerular hypertrophy and extracellular matrix (ECM) accumulation. Here, kidneys from diabetic model mice were investigated for the expression of the regulator of CaN 1 (RCAN1) isoform 4 (RCAN1.4) which had been shown to be transcriptionally upregulated by CaN activation. We found the increased immunoreactivity for RCAN1 in the glomerular cells of db/db mice and streptozotocin-induced diabetic mice. In concordance, the expression of RCAN1 protein and RCAN1.4 mRNA were elevated in the whole kidney sample from db/db mice. Interleukin-1? (IL-1?), tumor necrosis factor-?, and glycated albumin (AGE-BSA) were identified as inducers of RCAN1.4 in mesangial cells. Pretreatment of cyclosporine A blocked the increases of RCAN1.4 stimulated by IL-1? or AGE-BSA, suggesting that activation of CaN is required for the RCAN1.4 induction. Stable transfection of RCAN1.4 in Mes-13 mesangial cells upregulated several factors relevant to ECM production and degradation. These results suggested that RCAN1.4 might act as a link between CaN activation and ECM turnover in diabetic nephropathy. PMID:22128263

Jang, Chorong; Lim, Ji Hee; Park, Cheol Whee

2011-01-01

338

Non-viral systemic delivery of Fas siRNA suppresses cyclophosphamide-induced diabetes in NOD mice  

PubMed Central

A membrane receptor, Fas (CD95), and its ligand FasL have been considered as key players in diabetes pathogenesis. They are known to mediate interactions between ? cells and cytotoxic T cells, which results in apoptotic cell death. We hypothesized that the interruption of Fas-FasL interactions by suppressing Fas expression in ? cells would affect the development of diabetes. The effect of Fas-silencing siRNA (Fas siRNA) on the diabetes development was evaluated in a cyclophosphamide (CY)-accelerated diabetes animal model after intravenous administration using a polymeric carrier, polyethylenimine (PEI). The systemic non-viral delivery of Fas siRNA showed significant delay in diabetes incidence up to 40 days, while the control mice treated with naked Fas siRNA, scrambled dsRNA, or PBS were afflicted with diabetes within 20 days. The retardation of diabetes incidence after the treatment of Fas siRNA may be due to the delayed progression of the pancreatic insulitis. In this study, the potential use of a non-viral carrier based siRNA gene therapy for the prevention of type-1 diabetes is demonstrated. PMID:20004692

Jeong, Ji Hoon; Kim, Sun Hwa; Lee, Minhyung; Kim, Won Jong; Park, Tae Gwan; Ko, Kyung Soo; Kim, Sung Wan

2010-01-01

339

Decellularized silk fibroin scaffold primed with adipose mesenchymal stromal cells improves wound healing in diabetic mice  

PubMed Central

Introduction Silk fibroin (SF) scaffolds have been shown to be a suitable substrate for tissue engineering and to improve tissue regeneration when cellularized with mesenchymal stromal cells (MSCs). We here demonstrate, for the first time, that electrospun nanofibrous SF patches cellularized with human adipose-derived MSCs (Ad-MSCs-SF), or decellularized (D-Ad-MSCs-SF), are effective in the treatment of skin wounds, improving skin regeneration in db/db diabetic mice. Methods The conformational and structural analyses of SF and D-Ad-MSCs-SF patches were performed by scanning electron microscopy, confocal microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. Wounds were performed by a 5 mm punch biopsy tool on the mouse’s back. Ad-MSCs-SF and D-Ad-MSCs-SF patches were transplanted and the efficacy of treatments was assessed by measuring the wound closure area, by histological examination and by gene expression profile. We further investigated the in vitro angiogenic properties of Ad-MSCs-SF and D-Ad-MSCs-SF patches by affecting migration of human umbilical vein endothelial cells (HUVECs), keratinocytes (KCs) and dermal fibroblasts (DFs), through the aortic ring assay and, finally, by evaluating the release of angiogenic factors. Results We found that Ad-MSCs adhere and grow on SF, maintaining their phenotypic mesenchymal profile and differentiation capacity. Conformational and structural analyses on SF and D-Ad-MSCs-SF samples, showed that sterilization, decellularization, freezing and storing did not affect the SF structure. When grafted in wounds of diabetic mice, both Ad-MSCs-SF and D-Ad-MSCs-SF significantly improved tissue regeneration, reducing the wound area respectively by 40% and 35%, within three days, completing the process in around 10 days compared to 15–17 days of controls. RT2 gene profile analysis of the wounds treated with Ad-MSCs-SF and D-Ad-MSCs-SF showed an increment of genes involved in angiogenesis and matrix remodeling. Finally, Ad-MSCs-SF and D-Ad-MSCs-SF co-cultured with HUVECs, DFs and KCs, preferentially enhanced the HUVECs’ migration and the release of angiogenic factors stimulating microvessel outgrowth in the aortic ring assay. Conclusions Our results highlight for the first time that D-Ad-MSCs-SF patches are almost as effective as Ad-MSCs-SF patches in the treatment of diabetic wounds, acting through a complex mechanism that involves stimulation of angiogenesis. Our data suggest a potential use of D-Ad-MSCs-SF patches in chronic diabetic ulcers in humans. PMID:24423450

2014-01-01

340

Antioxidant and anti-diabetic potential of Passiflora alata Curtis aqueous leaves extract in type 1 diabetes mellitus (NOD-mice).  

PubMed

Leaves of Passiflora alata Curtis were characterized for their antioxidant capacity. Antioxidant analyses of DPPH, FRAP, ABTS, ORAC and phenolic compounds were made in three different extracts: aqueous, methanol/acetone and ethanol. Aqueous extract was found to be the best solvent for recovery of phenolic compounds and antioxidant activity, when compared with methanol/acetone and ethanol. To study the anti-inflammatory properties of this extract in experimental type 1 diabetes, NOD mice were divided into two groups: the P. alata group, treated with aqueous extract of P. alata Curtis, and a non-treated control group, followed by diabetes expression analysis. The consumption of aqueous extract and water ad libitum lasted 28 weeks. The treated-group presented a decrease in diabetes incidence, a low quantity of infiltrative cells in pancreatic islets and increased glutathione in the kidney and liver (p<0.05), when compared with the diabetic and non-diabetic control-groups. In conclusion, our results suggest that the consumption of aqueous extract of P. alata may be considered a good source of natural antioxidants and compounds found in its composition can act as anti-inflammatory agents, helping in the control of diabetes. PMID:24269180

Colomeu, T C; Figueiredo, D; Cazarin, C B B; Schumacher, N S G; Maróstica, M R; Meletti, L M M; Zollner, R L

2014-01-01

341

In vivo hypoglycaemic effect and inhibitory mechanism of the branch bark extract of the mulberry on STZ-induced diabetic mice.  

PubMed

Branch bark extract (BBE) derived from the mulberry cultivar Husang 32 (Morus multicaulis L.) with aqueous alcohol solution has been investigated as an inhibitor of ?-glycosidase in vitro. Mulberry BBE was orally administered to STZ-induced diabetic mice for three weeks, and it improved the weight gain and ameliorated the swelling of liver and kidney in diabetic mice. Obviously, mulberry BBE not only can reduce the abnormally elevated levels of serum insulin and ameliorate insulin resistance induced by STZ, but also it regulates dyslipidemia in diabetic mice. To understand this therapeutic effect and the regulatory mechanisms of BBE in diabetic mice, a qRT-PCR experiment was performed, indicating that the mulberry BBE can regulate the mRNA expression of glycometabolism genes in diabetic mice, including glucose-6-phosphatase (G6Pase), glucokinase (GCK), and phosphoenolpyruvate carboxykinase (PEPCK), thereby regulating sugar metabolism and reducing the blood glucose level in diabetic mice. The mulberry BBE can increase the mRNA expression of the genes Ins1, Ins2 and pancreatic duodenal homeobox-1 (PDX-1) and may decrease the insulin resistance in diabetic mice. Those results provide an important basis for making the best use of mulberry branch resources and producing biomedical drugs with added value. PMID:25177729

Liu, Hua-Yu; Fang, Meng; Zhang, Yu-Qing

2014-01-01

342

Global biochemical profiling identifies beta-hydroxypyruvate as a potential mediator of type 2 diabetes in mice and humans.  

PubMed

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like pepide-1 (GLP-1) are incretins secreted by respective K and L enteroendocrine cells after eating and amplify glucose-stimulated insulin secretion (GSIS). This amplification has been coined the "incretin response". To determine the role(s) of K cells for the incretin response and T2DM, "DT" mice lacking GIP-producing cells were backcrossed 5 to 8 times onto the diabetogenic NONcNZO10/Ltj background. Like humans with T2DM, DT mice lacked an incretin response although GLP-1 release was maintained. With high fat (HF) feeding, DT mice remained lean but developed T2DM whereas WT mice developed obesity but not diabetes. Metabolomics identified biochemicals reflecting impaired glucose handling, insulin resistance, and diabetic complications in pre-diabetic DT/HF mice. Beta-hydroxypyruvate and benzoate levels were increased and decreased, respectively, suggesting beta-hydroxypyruvate production from D-serine. In vitro, beta-hydroxypyruvate altered excitatory properties of myenteric neurons and reduced islet insulin content but not GSIS. Beta-hydroxypyruvate/D-serine ratios were lower in humans with impaired glucose tolerance compared to normal glucose tolerance and T2DM. Earlier human studies unmasked a neural relay that amplifies GIP-mediated insulin secretion in a pattern reciprocal to beta-hydroxypyruvate/D-serine ratios in all groups. Thus, K cells may maintain long-term function of neurons and beta cells by regulating beta-hydroxypyruvate levels. PMID:25368100

Zhang, Sheng; Wang, Songyan; Puhl, Matthew D; Jiang, Xuntian; Hyrc, Krzysztof L; Laciny, Erin; Wallendorf, Michael J; Pappan, Kirk L; Coyle, Joseph T; Wice, Burton M

2014-11-01

343

Sodium Meta-Arsenite Ameliorates Hyperglycemia in Obese Diabetic db/db Mice by Inhibition of Hepatic Gluconeogenesis  

PubMed Central

Sodium meta-arsenite (SA) is implicated in the regulation of hepatic gluconeogenesis-related genes in vitro; however, the effects in vivo have not been studied. We investigated whether SA has antidiabetic effects in a type 2 diabetic mouse model. Diabetic db/db mice were orally intubated with SA (10?mg?kg?1 body weight/day) for 8 weeks. We examined hemoglobin A1c (HbA1c), blood glucose levels, food intake, and body weight. We performed glucose, insulin, and pyruvate tolerance tests and analyzed glucose production and the expression of gluconeogenesis-related genes in hepatocytes. We analyzed energy metabolism using a comprehensive animal metabolic monitoring system. SA-treated diabetic db/db mice had reduced concentrations of HbA1c and blood glucose levels. Exogenous glucose was quickly cleared in glucose tolerance tests. The mRNA expressions of genes for gluconeogenesis-related enzymes, glucose 6-phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK) were significantly reduced in the liver of SA-treated diabetic db/db mice. In primary hepatocytes, SA treatment decreased glucose production and the expression of G6Pase, PEPCK, and hepatocyte nuclear factor 4 alpha (HNF-4?) mRNA. Small heterodimer partner (SHP) mRNA expression was increased in hepatocytes dependent upon the SA concentration. The expression of Sirt1 mRNA and protein was reduced, and acetylated forkhead box protein O1 (FoxO1) was induced by SA treatment in hepatocytes. In addition, SA-treated diabetic db/db mice showed reduced energy expenditure. Oral intubation of SA ameliorates hyperglycemia in db/db mice by reducing hepatic gluconeogenesis through the decrease of Sirt1 expression and increase in acetylated FoxO1. PMID:25610880

Lee, Eun-Kyu; Oh, Hyun-Hee; Choi, Cheol Soo; Kim, Sujong; Jun, Hee-Sook

2014-01-01

344

Defects in the Acquisition of Tumor-Killing Capability of CD8+ Cytotoxic T Cells in Streptozotocin-Induced Diabetic Mice  

PubMed Central

Emerging evidences have shown that diabetes mellitus not only raises risk but also heightens mortality rate of cancer. It is not clear, however, whether antitumor CD8+ cytotoxic T lymphocyte (CTL) response is down-modulated in diabetic hosts. We investigated the impact of hyperglycemia on CTLs' acquisition of tumor-killing capability by utilizing streptozotocin-induced diabetic (STZ-diabetic) mice. Murine diabetes was induced by intraperitoneal injection of STZ (200 mg/kg) in C57BL/6 mice, 2C-T cell receptor (TCR) transgenic and P14-TCR transgenic mice. The study found that, despite harboring intact proliferative capacity measured with CFSE labeling and MTT assay, STZ-diabetic CD8+ CTLs displayed impaired effector functions. After stimulation, STZ-diabetic CD8+ CTLs produced less perforin and TNF? assessed by intracellular staining, as well as expressed less CD103 protein. Furthermore, adoptive transfer of STZ-diabetic P14 CD8+ effector cells showed an insufficient recruitment to the B16.gp33 melanoma and inadequate production of perforin, granzyme B and TNF? determined by immunohistochemistry in the tumor milieu. As a result, STZ-diabetic CD8+ effector cells were neither able to eliminate tumor nor to improve survival of tumor-bearing mice. Taken together, our data suggest that CD8+ CTLs are crippled to infiltrate into tumors and thus fail to acquire tumor-killing capability in STZ-diabetic hosts. PMID:25390652

Chen, Shu-Ching; Su, Yu-Chia; Lu, Ya-Ting; Ko, Patrick Chow-In; Chang, Pei-Yu; Lin, Hung-Ju; Ho, Hong-Nerng; Lai, Yo-Ping

2014-01-01

345

Involvement of c-myc in the resistance of non-obese diabetic mice to glucocorticoid-induced apoptosis.  

PubMed Central

Non-obese diabetic (NOD) mice spontaneously develop insulin-dependent diabetes mellitus (IDDM) as a consequence of autoimmune aggression of beta cells of the endocrine pancreas by T cells. T lymphocytes of NOD mice are resistant to apoptosis induced by glucocorticoids, or by starving or DNA-damaging treatments, a feature that was interpreted as being linked to escape of autoreactive T cells from thymic negative selection. c-myc is one of the gene targets of glucocorticoids (GC), its expression being down-regulated by the activated GC-GC receptor complex. We investigated here whether expression of Myc protein, in response to dexamethasone stimulation, was the same in NOD mice and in non-autoimmune strains, namely NON, BALB/c and C57Bl.6. We found a consistent increase in the levels of Myc protein after GC-treatment of lymphocytes of NOD mice, a finding that was in contrast to the down-regulation of c-myc that we observed in lymphocytes from mice not prone to diabetes. We also report that, rather than a absolute resistance to GC-induced cell death, NOD mice display a delayed apoptotic response to GC. We propose that the resistance of NOD mice lymphocytes to GC-induced apoptosis is because of inhibition of the repressive action of GC-GR complexes at the level of c-myc transcription. This deficient action of GC-GR results in increased production of nuclear Myc protein, peculiar to NOD mice cells, following their treatment with GC. Images Figure 3 Figure 4 Figure 5 PMID:9824500

Martins, T C; Aguas, A P

1998-01-01

346

Induction of intramembranous particle clusters in mice with nephrogenic diabetes insipidus.  

PubMed

In mice with hereditary nephrogenic diabetes insipidus (NDI), the inability of vasopressin to increase hydraulic water permeability is reflected in a lack of intramembranous particle (IMP) clusters in apical membranes of inner medullary collecting ducts. The lack arises from anomalously high activity of one or two isozymes of adenosine 3',5'-cyclic monophosphate-phosphodiesterase (cAMP-PDE). We asked whether inhibition of these isozymes with rolipram and cilostamide would raise not only the tissue content of cAMP but also and simultaneously restore IMP clusters. Inner medullary collecting ducts from NDI mice were incubated in vitro. Tissue content of cAMP (fmol of cAMP per bundle) and number of IMP clusters (per 100 microns 2 of principal cell apical membrane) were, respectively: control, 44.8 +/- 13.0 and 4.16 +/- 1.49; arginine vasopressin (AVP), 31.7 +/- 8.0 and 3.98 +/- 1.56; rolipram and cilostamide, 109.7 +/- 21.0 and 58.09 +/- 15.74; and AVP plus rolipram and cilostamide, 305.7 +/- 75 and 48.63 +/- 11.03 (with the last four values showing significant difference from control and AVP only, respectively). In addition, treating NDI mice with rolipram and cilostamide in vivo reduced their high fluid turnover. We conclude that failure by AVP to increase cAMP in cells of collecting ducts, which results from anomalously high activity of one or two specific isozymes of cAMP-PDE, is the major or sole cause for the excretion of hypotonic urine in NDI mice (DI +/+ Severe strain). PMID:1656782

Coffey, A K; O'Sullivan, D J; Homma, S; Dousa, T P; Valtin, H

1991-10-01

347

Islet-specific T-cell clones from nonobese diabetic mice express heterogeneous T-cell receptors.  

PubMed Central

Nonobese diabetic (NOD) mice spontaneously develop a T-cell-mediated autoimmune disease that is similar in many respects to insulin-dependent diabetes mellitus in humans. T-cell clones that specifically recognize pancreatic islet cell antigens can be derived from NOD mice, and most of these have been diabetogenic upon transfer to healthy recipients. We report herein the sequences of the T-cell receptor alpha and beta chains from four NOD-derived, islet-specific clones. The sequences are quite heterogeneous--in the junctional regions, specifically--so there seems to be little hope for treating this disease with specific anti-T-cell receptor reagents. This result contrasts with the strikingly restricted junctional region sequences reported for the receptors on clones derived from mice with experimental allergic encephalomyelitis, another T-cell-mediated autoimmune disease. We discuss possible explanations for this difference. PMID:2068098

Candéias, S; Katz, J; Benoist, C; Mathis, D; Haskins, K

1991-01-01

348

Effects of Hydro-Alcoholic Extract of Rhus coriaria (Sumac) Seeds on Reproductive Complications of Nicotinamide-Streptozotocin Induced Type-2 Diabetes in Male Mice  

PubMed Central

Purpose The purpose of this study was to investigate the effects of the hydro-alcoholic extract of Rhus coriaria seeds on the reproductive system of nicotinamide-streptozotocin-induced type-2 diabetic mice. Materials and Methods In this experimental study, 56 male Naval Medical Research Institute mice were randomly divided into seven groups (n=8): control; diabetic mice; diabetic mice administered glibenclamide (0.25 mg/kg); diabetic mice who received the hydro-alcoholic extract of R. coriaria seeds (200 and 400 mg/kg groups); and normal mice who received this extract (200 and 400 mg/kg groups). Diabetes was induced by intraperitoneal administration of streptozotocin (65 mg/kg) 15 minutes after an injection of nicotinamide (120 mg/kg). Then, glibenclamide and the above mentioned extract were administered orally for 28 consecutive days. Twenty-four hours after the last treatment, serum samples, the testes, and the cauda epididymis were removed immediately for hormonal, testis morphology, and sperm parameter assessments. Results Body and testicular weight, sperm count and viability, and serum luteinizing hormone, follicle-stimulating hormone and testosterone levels were significantly lower in the diabetic mice (p<0.05). The diabetic mice treated with 400 mg/kg of the hydro-alcoholic extract of R. coriaria seeds recovered from these reductions (p<0.05). Further, glibenclamide alleviated hormonal and sperm count depletion in diabetes-induced mice (p<0.05). Conclusions The present results indicated that the hydro-alcoholic extract of R. coriaria seeds has anti-infertility effects in diabetic males. PMID:25606564

Ahangarpour, Akram; Heidari, Hamid; Ehsan, Ghaedi; Rashidi Nooshabadi, Mohammad Reza

2014-01-01