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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

Antihyperglycemic effects of fermented and nonfermented mung bean extracts on alloxan-induced-diabetic mice.  

PubMed

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

2012-10-03

3

Semicarbazide-sensitive amine oxidase (SSAO) gene expression in alloxan-induced diabetes in mice.  

PubMed Central

BACKGROUND: Plasma activity of semicarbazide-sensitive amine oxidase (SSAO) has been reported to be significantly higher in diabetic patients compared to healthy controls. Due to the production of highly angiotoxic substances in SSAO-catalyzed reactions, it has been speculated that this could be a cause for the vascular complications frequently associated with diabetes. Little is known about how the enzyme activity is regulated, and why it is high in these patients. In the present study, we assessed the possibility of transcriptional regulation by analyzing SSAO activity and SSAO-mRNA levels in mice with alloxan-induced diabetes. MATERIALS AND METHODS: Diabetes was induced in NMRI mice by a single intravenous injection of alloxan. The enzyme activity was analyzed by a radiometric assay using (14) C-benzylamine as a substrate, and the mRNA-levels were analyzed by real-time PCR. RESULTS: We found that the enzyme activity was increased in lung and adipose tissue 1 day after induction, as the glucose levels start to rise. Seven days after the injection of alloxan, the activity in serum was increased, and this activity was positively correlated with blood glucose levels in the alloxan-treated animals. Although the enzyme activity was increased in adipose tissue as a result of the treatment, SSAO-mRNA levels in this tissue were decreased, possibly suggesting a negative feedback on the gene expression. CONCLUSIONS: The main conclusion from this study is that the increased enzyme activity observed in diabetes is not a result of increased SSAO gene transcription. We speculate that the enzyme activity is controlled by posttranslational modifications of the protein, and that the catalytic activity controls the gene expression.

Nordquist, Jenny E. L.; Gokturk, Camilla; Oreland, Lars

2002-01-01

4

Efficacy of chitooligosaccharides for the management of diabetes in alloxan induced mice: a correlative study with antihyperlipidemic and antioxidative activity.  

PubMed

The present study evaluates the effects of chitooligosaccharides (COS) for the management of alloxan induced diabetes in mice. For the management of the carbohydrate metabolism in diabetes by the COS, the amount of glucose in blood along with quantification of glycogen in liver were measured and noted a significant recovery in respect to diabetic control group. As hyperlipidemia and oxidative stress are the disorders of diabetes so, we have also assessed the serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLc), very low density lipoprotein cholesterol (VLDLc) and high density lipoprotein cholesterol (HDLc). For the recovery of oxidative stress the SOD MDA catalase in liver and GOT and GPT activities in serum were measured. The COS results a significant recovery in the levels of above mentioned biosensors of lipid profile when treated to experimentally induce diabetic mice. The effect of COS at the dose of 10mg/kg body weight was found to be a potent agent for diabetes and complication associated with this disease. The COS has no toxic effect in general which has been focused here by the monitoring of COS dose in normal healthy mice. The results of this study enlighted that the COS has antidiabetic, antihyperlipidemic and antioxidative activities. PMID:21964204

Katiyar, Deepmala; Singh, Bharati; Lall, Alok Milton; Haldar, Chandana

2011-09-22

5

Antihyperglycemic and antioxidative potential of hydroalcoholic extract of Butea monosperma Lam flowers in alloxan-induced diabetic mice.  

PubMed

Daily treatment of alloxan-induced diabetic animals with 50% ethanolic extract of B. monosperma flowers (BMEE) for 45 days significantly lowered blood glucose level thereby preventing steep onset of hyperglycemia which was observed after alloxan administration and maintained body weight and blood glucose level close to the values observed in normal control and glibenclamide-treated diabetic mice. Moreover, the level of serum total cholesterol, triglyceride, low-density lipoprotein and very low-density lipoprotein cholesterol were also lowered, whereas the level of high-density lipoprotein cholesterol, which was reduced in untreated diabetic animals, was significantly elevated. Oxidative damage in the liver, pancreas and kidneys of diabetic mice as evidenced by a marked increment in the level of thiobarbituric acid reactive substances and also a distinct diminution in glutathione content was nullified by BMEE. Activities of antioxidant enzymes were also assessed in all the experimental groups. These enzymes registered a decline in their activity in diabetic animals thus revealing the damaging effects of free radicals generated due to alloxan exposure but their activities were reverted towards near normal range in BMEE-administered mice thus indicating the antioxidant efficacy of the drug in resisting oxidative damage. PMID:19761041

Sharmna, Nidhi; Garg, Veena

2009-07-01

6

Hypoglycemic activity of the Anisopus mannii N. E. Br. methanolic leaf extract in normal and alloxan-induced diabetic mice.  

PubMed

The hypoglycemic activities of nine sub-fractions from the methanolic leaf crude extract of Anisopus mannii were investigated in normoglycemic and alloxan-induced diabetic mice. The methanolic sub-fraction M at 400 mg/kg bw showed significantly (p<0.05) high reduction in fasting blood glucose (FBG) at 27.36 and 65.57% in normoglycemic and diabetic mice, respectively. In acute toxicity test, M at 2,000 and 5,000 mg/kg bw showed reduction in blood urea nitrogen and creatinine level, elevations in aspartate transaminase, alanine transaminase and total bilirubin levels, as well as the body weights. The weight-ratios of kidney and liver to the body weight of the mice fed with these doses of M were reduced with no sign of histopathological alteration. The M at 250 mg/kg bw significantly reduced the FBG levels in a postprandial study. The hypoglycemic effect of M was eliminated when co-administered with isosorbide dinitrate or nifedipine indicating the induction of insulin secretion via K+ ATP-dependent channels. The UV/HPLC analysis of M indicated saponin at 7.7 mg/g. This study confirmed the traditional use of A. mannii for diabetes mellitus and the potential for the further development as a novel hypoglycemic drug. PMID:23828328

Zaruwa, Moses Z; Manosroi, Aranya; Akihisa, Toshihiro; Manosroi, Worapaka; Rangdaeng, Samreung; Manosroi, Jiradej

2013-06-26

7

Hypoglycemic Properties of Oxovanadium (IV) Coordination Compounds with Carboxymethyl-Carrageenan and Carboxymethyl-Chitosan in Alloxan-Induced Diabetic Mice  

PubMed Central

In order to avoid low absorption, incorporation, and undesirable side effects of inorganic oxovanadium compounds, the antidiabetic activities of organic oxovanadium (IV) compounds in alloxan-induced diabetic mice were investigated. Vanadyl carboxymethyl carrageenan (VOCCA) and vanadyl carboxymethyl chitosan (VOCCH) were synthesized and administrated through intragastric administration in different doses for 20 days in alloxan-induced diabetic mice. Glibenclamide was administrated as the positive control. Our results showed that low-dose group, middle-dose group, and high-dose group of VOCCA and VOCCH could significantly reduce the levels of blood glucose (P < 0.05) compared with untreated group, but not in normal mice. Besides, high-dose groups of VOCCA and VOCCH exhibited more significant hypoglycemic activities (P < 0.01). After treated with VOCCH, the oral glucose tolerance of high-dose group of VOCCH was improved compared with model control group (P < 0.05).

Zhang, Hongyu; Yi, Yuetao; Feng, Dawei; Wang, Yipeng; Qin, Song

2011-01-01

8

Regenerative potential of pancreata in alloxan induced diabetic mice by 4-Hydroxyisoleucine, comparision with pioglitazone  

Microsoft Academic Search

Hydroxyisoleucine (4HI) isolated from seeds of fenugreek produced antihyperglycaemic effects in diabetic mice. However, its role in pancreatic regeneration is not well understood. The objective of the present study was to evaluate the antihyperglycaemic, pancreatic regenerative potential of 4HI and compare it with pioglitazone. Alloxan (80 mg\\/kg, i.v.) induced diabetic mice were fed orally with 4HI (40 mg\\/kg) once a

Shweta Shah; Subhash Bodhankar; Ramesh Bhonde; V Mohan

2009-01-01

9

Prevention of Alloxan-Induced Diabetes Mellitus in the Rat by Silymarin  

Microsoft Academic Search

Silymarin is a free-radical scavenger and a membrane stabilizer which prevents lipoperoxidation and its associated cell damage in some experimental models. It has been proposed that lipid peroxidation caused by free radicals may be involved in alloxan-induced diabetes mellitus. Alloxan elicits pancreatic lipid peroxidation which precedes the appearance of hyperglycemia in mice. We studied the effects of silymarin on rat

Claudia P Soto; Blanca L Perez; Liliana P Favari; Jose L Reyes

1998-01-01

10

Ethanolic extract of Crinum asiaticum attenuates hyperglycemia-mediated oxidative stress and protects hepatocytes in alloxan induced experimental diabetic rats  

Microsoft Academic Search

The present study is to investigate the antioxidant activity in alloxan induced diabetic rats. The experimental rats were randomly divided into three groups: Group I: control; Group II: alloxan induced diabetic rats and Group III: alloxan induced diabetic rats were treated with ethanolic extract of Crinum asiaticum leaves (200mg\\/kg\\/bw). Diabetes mellitus was induced by alloxan in a single dose of

S. Indradevi; S. Ilavenil; B. Kaleeswaran; S. Srigopalram; S. Ravikumar

11

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

Microsoft Academic Search

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

R. Punitha; S. Manoharan

2006-01-01

12

AntiDiabetic Activity of Terminalia Catappa Linn. Leaf Extracts in Alloxan-Induced Diabetic Rats  

Microsoft Academic Search

In view of suggested anti diabetic potential, effect of aqueous and cold extracts of Terminalia Catappa Linn (Combretaceae) leaves, on fasting blood sugar levels and serum biochemical analysis in alloxan- induced diabetic rats was investigated. All the extracts of Terminalia Catappa produced a significant anti diabetic activity at dose levels of 1\\/5 th of their lethal doses. Concurrent histological studies

SYED MANSOOR AHMED; VRUSHABENDRA SWAMY BM; P GOPKUMAR; R DHANAPAL

13

Effects of brazilin on blood viscosity and erythrocyte deformability in alloxan induced diabetic rats  

Microsoft Academic Search

Effects of brazilin on the blood viscosity and erythrocyte deformability were investigated in alloxan induced diabetic rats.\\u000a By the treatment of brazilin to alloxan induced diabetic rats, enhancement of erythrocyte deformability was observed. In thein vitro study on the erythrocyte deformability, brazilin showed statistically significant improving effects on the erythrocyte deformability.\\u000a At the concentrations of 10?3M of brazilin, erythrocyte deformability

Chang-Kiu Moon; Jin-Ho Chung; Seong-Soo Choi; Soo-Hwan Lee; Gwi-Seo Hwang; Kwang-Sik Park; Myung-Soo Mock; Seong-Gon Kim; Ji-Young Kim

1988-01-01

14

EFFECTS OF CHRONIC TREATMENT WITH CROMAKALIM AND GLIBENCLAMIDE IN ALLOXAN-INDUCED DIABETIC RATS  

Microsoft Academic Search

We have studied the effects of chronic treatment with cromakalim (75ugkg?1 per day) and glibenclamide (20mgkg?1 per day) in alloxan-induced diabetic rats. Injection of alloxan (60mgkg?1\\/i.v., single dose) produced a significant increase in the blood pressure, bradycardia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypothyroidism and depression in left ventricular developed pressure (LVDP). While glibenclamide significantly prevented alloxan-induced hyperglycemia and hypoinsulinaemia, it failed to

JAYANT S. KULKARNI; ANITA A. METHA; DEV D. SANTANI; RAMESH K. GOYAL

2002-01-01

15

Antioxidant Effect of Tinospora cordifolia Extract in Alloxan-induced Diabetic Rats  

PubMed Central

Many plants are claimed to possess antidiabetic and antioxidant activity. In practice, it is being increasingly recognized to be an alternative approach to modern medicine. This study assess the antioxidant capacity of Tinospora cordifolia stem methanol extract in daily oral administration of 500 mg/kg of body weight for 40 days in alloxan induced diabetic rats. The erythrocytes membrane lipid peroxide and catalase activity was increased where as the activities of superoxide dismutase, glutathione peroxidase were found to be decreased significantly (P<0.01) in alloxan-induced diabetic rats. The levels of lipid peroxide in liver of diabetic rats increased significantly (P<0.01) and catalase, superoxide dismutase, glutathione peroxidase in liver was significantly decreased in alloxan-induced diabetic rats, when compared to normal rats. After treatment of methanol Tinospora cordifolia stem extract brings back to normal (P<0.01) in the erythrocytes membrane and liver cell enzymes activities.

Sivakumar, V.; Rajan, M. S. Dhana

2010-01-01

16

ANTIHYPERGLYCEMIC EFFECTS OF BERBERIS LYCEUM ROYLE IN ALLOXAN INDUCED DIABETIC RATS  

Microsoft Academic Search

SUMMARY Berberis lyceum is a medicinal shrub used in conventional therapy for a number of diseases including diabetes mellitus. The aim of the present study was to investigate the antihyperglycemic effects of aqueous and ethanol extracts of Berberis lyceum in alloxan induced diabetic and normal rats. Rats were administered 50 and 100 mg\\/kg of aqueous and ethanol root extracts and

Muhammad Gulfraz; Ghulam Qadir; Fatima Nosheen; Zahida Parveen

2007-01-01

17

Antioxidant activity of Cassia fistula (Linn.) flowers in alloxan induced diabetic rats  

Microsoft Academic Search

Aqueous extract of Cassia fistula (Linn.) flowers (ACF) was screened for its antioxidant effect in alloxan induced diabetic rats. An appreciable decrease in peroxidation products viz thiobarbituric acid reactive substances, conjugated dienes, hydroperoxides was observed in heart tissues of ACF treated diabetic rats. The decreased activities of key antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and

G. Manonmani; V. Bhavapriya; S. Kalpana; S. Govindasamy; T. Apparanantham

2005-01-01

18

Immunomodulatory effects of black seeds and garlic on alloxan-induced Diabetes in albino rat  

Microsoft Academic Search

BackgroundAlteration in the proliferation capacity of leukocytes and in the level of some cytokines, such as TNF-?, IL-4 and IL-8 have been suggested to associate with Diabetes mellitus in alloxan-induced diabetic rats given the potential immunomodulatory effects of black seeds and garlic.

Bahaa K. A. Abel-Salam

19

Antidiabetic activity of levan polysaccharide in alloxan-induced diabetic rats  

Microsoft Academic Search

This study aims to examine the effects of polysaccharide levan on oxidative stress and hyperglycemia in alloxan-induced diabetic rats. Levan, used in this study, was a microbial levan synthetisized by a non pathogenic bacteria recently isolated and identified as Bacillus licheniformis. Animals were allocated into four groups of six rats each: a control group (Control), diabetic group (Diab.), normal rats

Imen Dahech; Karima Srih Belghith; Khaled Hamden; Abdelfattah Feki; Hafedh Belghith; Hafedh Mejdoub

2011-01-01

20

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

21

Antihyperglycemic effect of Diospyros melanoxylon (Roxb.) bark against Alloxan-induced diabetic rats  

Microsoft Academic Search

The antihyperglycemic activity of Diospyros melanoxylon (Roxb.) bark was evaluated with scientific approach including biochemical parameters and histopathological studies of pancreas. The ethanolic extracts of the powdered bark was tested for its efficacy in alloxan-induced diabetic rats. The extracts were also evaluated for acute oral toxicity studies and its effect on different biochemical parameters. An effect of extracts was compared

Jadhav J. K; M. S. India

22

Silymarin increases antioxidant enzymes in alloxan-induced diabetes in rat pancreas  

Microsoft Academic Search

The aim of this study was to analyze the effect of the flavonoid silymarin, a free radical scavenger that prevents lipoperoxidation, on the pancreatic activity of superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT) in rats with alloxan-induced diabetes mellitus. Alloxan intoxicated rats were treated with silymarin in two manners, simultaneously (four or eight doses) or 20 days after

Claudia Soto; Rosa Recoba; Héctor Barrón; Carlos Alvarez; Liliana Favari

2003-01-01

23

Studies on Cataractogenesis in Humans and in Rats with Alloxan-Induced Diabetes  

Microsoft Academic Search

The effect of cataractogenesis on the behavior of some enzymes involved in glucose metabolism was examined histochemically both in human lenses and in rat lenses from rats with alloxan-induced diabetes. Several modifications in the currently available techniques were made in order to localize glucose-6-phosphate dehydrogenase, aldose reductase, sorbitol dehydrogenase, hexokinase and ketohexokinase in ocular lens. Human cataractous lenses showed a

S. S. Ahmad; K. C. Tsou; S. I. Ahmad; M. Ataur Rahman

1985-01-01

24

Antidiabetic Activity of Ethanolic Extract of Zaleya decandra in Alloxan-Induced Diabetic Rats  

Microsoft Academic Search

Diabetes mellitus is a complex disorder that disturbs the metabolism of carbohydrates, fats, and proteins. Medicinal plants\\u000a play an important role in the management of diabetes mellitus. The present study was aimed to evaluate the antidiabetic potential\\u000a of Zaleya decandra roots on alloxan-induced diabetes in rats. Oral administration of ethanolic extract of the root (200 mg\\/kg body weight\\/day)\\u000a for 15 days restored

Periasamy Meenakshi; Rajendran Bhuvaneshwari; Muthaiyan Ahalliya Rathi; Lakshmanan Thirumoorthi; Dugganaboyana Chinna Guravaiah; Muthedath Janardhanan Jiji; Velliyur Kanniappan Gopalakrishnan

2010-01-01

25

Effects of iscador and vincristine and 5-fluorouracil on brain, liver, and kidney element levels in alloxan-induced diabetic mice.  

PubMed

Exposure to substance toxicity is especially dangerous for diabetics because it accelerates and intensifies diabetic complication. Homeostasis of trace elements can be disrupted by diabetes mellitus. On the other hand, disturbance in trace element status in diabetes mellitus may contribute to insulin resistance and development of diabetic complications. The aim of the present study was to compare the concentration of elements in the brain, liver, and kidneys of animals with induced diabetes after the administration of plant preparations (iscador and vincristine) and 5-fluorouracil. The experiments were carried out on male mice. The animals were divided into five groups of ten mice each: one control and four experimental groups. The first experimental group was administered alloxan at 75 mg/kg b.w. for 4 days, the second group was administered both alloxan at 75 mg/kg b.w. and vincristine 1 mg/kg b.w. for 4 days, and the third group was administered both alloxan at 75 mg/kg b.w. and 5-fluorouracil 75 mg/kg b.w. for 4 days. The animals of the fourth group were administered both alloxan at 75 mg/kg b.w. and iscador Qu at 5 mg/kg b.w. for 4 days. Calcium, magnesium, iron, copper, zinc, sodium, and potassium levels in the tissues were analyzed by flame atomic absorption spectrophotometer. We observed that zinc, copper, magnesium, sodium, and potassium were lower in the brain as compared to the control animals. The copper levels in the liver were also lower in diabetic groups than in control groups. However, the iscador and vincristine and 5-fluorouracil did not induce significant differences in the five groups. In conclusion, results of the current study indicated that changes of the investigated essential elements may contribute to explaining the role of impaired element metabolism of some elements in the progression of diabetic complications. PMID:23334865

Gre?, Agnieszka; Formicki, Grzegorz

2013-01-19

26

Hypoglicemic effect of Leandra lacunosa in normal and alloxan-induced diabetic rats  

Microsoft Academic Search

Leandra lacunosa, popularly known as “erva-do-jabuti”, is used in Brazilian folkloric medicine for the treatment of diabetes mellitus. Based on this traditional indication, the aim of this work was to evaluate the hypoglycemic activity of the hydroalcoholic extract of L. lacunosa aerial parts (LLH) in normal and alloxan-induced diabetic rats. Chromatographic fractionation of LLH was also carried out by several

W. R. Cunha; G. M. Arantes; D. S. Ferreira; R. Lucarini; M. L. A. Silva; N. A. J. C. Furtado; A. A. da Silva Filho; A. E. M. Crotti; A. R. B. Araújo

2008-01-01

27

Biochemical study on the hypoglycemic effects of onion and garlic in alloxan-induced diabetic rats  

Microsoft Academic Search

The present study was carried out to investigate the effects of onion (Allium cepa Linn) and garlic (Allium sativum Linn) juices on biochemical parameters, enzyme activities and lipid peroxidation in alloxan-induced diabetic rats. Alloxan was administered as a single dose (120mg\\/kgBW) to induce diabetes. A dose of 1ml of either onion or garlic juices\\/100g body weight (equivalent to 0.4g\\/100gBW) was

F. M. El-Demerdash; M. I. Yousef; N. I. Abou El-Naga

2005-01-01

28

Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus  

Microsoft Academic Search

Electrolyzed reduced water, which is capable of scavenging reactive oxygen species, is attracting recent attention because\\u000a it has shown improved efficacy against several types of diseases including diabetes mellitus. Alloxan produces reactive oxygen\\u000a species and causes type 1 diabetes mellitus in experimental animals by irreversible oxidative damage to insulin-producing\\u000a ?-cells. Here, we showed that electrolyzed reduced water prevented alloxan-induced DNA

Yupin Li; Takeki Hamasaki; Noboru Nakamichi; Taichi Kashiwagi; Takaaki Komatsu; Jun Ye; Kiichiro Teruya; Masumi Abe; Hanxu Yan; Tomoya Kinjo; Shigeru Kabayama; Munenori Kawamura; Sanetaka Shirahata

2011-01-01

29

ACTION OF CAPPARIS DECIDUA AGAINST ALLOXAN-INDUCED OXIDATIVE STRESS AND DIABETES IN RAT TISSUES  

Microsoft Academic Search

Alloxan-induced diabetic rats were treated with insulin (i.p.) or withCapparis deciduapowder as a hypoglycaemic agent mixed with diet. The effect was assessed on lipid peroxidation (LPO) and the antioxidant defense system in rat tissues. The increased levels of blood glucose in diabetes produce superoxide anions and hydroxyl radicals in the presence of transition metal ions which cause oxidative damage to

POONAM YADAV; SHUBASHISH SARKAR; DEEPAK BHATNAGAR

1997-01-01

30

Paradoxical effects of a selective cyclooxygenase-2 inhibitor, etodolac, on proliferative changes of forestomach in alloxan-induced diabetic rats  

Microsoft Academic Search

A single intravenous injection of alloxan, a non-genotoxic diabetogenic chemical, induces proliferative changes in forestomach mucosa of rats, and some lesions progress to squamous cell carcinoma accompanied with inflammatory change. The present study was conducted to examine the effects of a selective cyclooxygenase-2 (COX-2) inhibitor, etodolac, on the proliferative changes of forestomach mucosa in alloxan-induced diabetic rats. Alloxan-induced diabetic rats

Tomoya Sano; Kiyokazu Ozaki; Yasushi Kodama; Tetsuro Matsuura; Isao Narama

2009-01-01

31

Antihyperglycemic and hypoglycemic effect of Aporosa lindleyana in normal and alloxan induced diabetic rats  

Microsoft Academic Search

The hypoglycemic effect of aqueous and alcoholic extracts of root of Aporosa lindleyana was investigated in both normal and alloxan induced diabetic rats. The blood glucose levels were measured at 0, 1, 2 and 3 h after the treatment. The aqueous and alcoholic extracts of A. lindleyana (100 mg\\/kg) reduced the blood glucose of normal rat from 80.4±2.7 to 69.8±2.0

B. Jayakar; B. Suresh

2003-01-01

32

Comparative evaluation of antidiabetic activity of some marketed polyherbal formulations in alloxan induced diabetic rats  

Microsoft Academic Search

A comparison was made between the antidiabetic activities of five different marketed polyherbal formulations in alloxan induced diabetic rats. Serum glucose and other biochemical parameters i.e. total protein, triglyceride and cholesterol were determined at the dose 800 mg\\/kg body weight, p.o. for 30 days. There is a significant increase in serum glucose (p<0.001) and improvement in the other biochemical parameters

C. R. Tenpe; P. G. Yeole

33

Biochemical study on the effects of some Egyptian herbs in alloxan-induced diabetic rats  

Microsoft Academic Search

The present study was carried out to investigate the effects of Lupinus albus, L. (Lupinus termis), family L. leguminosae, Cymbopogon proximus, (Halfa barr), family Gramineae, and Zygophyllum coccineum L. (Kammun quaramany), family L. Zygophyllacae on biochemical parameters in alloxan-induced diabetic rats. A dose of 1.5 ml of aqueous suspension of each herb\\/100 g body weight (equivalent to 75 mg\\/100 g

Hamdy A Mansour; Al-Sayeda A Newairy; M. I Yousef; S. A Sheweita

2002-01-01

34

Antidiabetic effect of T. arjuna bark extract in alloxan induced diabetic rats  

Microsoft Academic Search

The present study was carried out to evaluate the antidiabetic effect of T. arjuna stembark extract and to study the activities\\u000a of hexokinase, aldolase and phosphoglucoisomerase, and gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-diphosphatase\\u000a in liver and kidney of normal and alloxan induced diabetic rats. Oral administration of ethanolic extract of bark (250 and\\u000a 500mg\\/kg body weight) for 30 days,

B. Ragavan; S. Krishnakumari

2006-01-01

35

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

36

Antidiabetic Activity of Vinca rosea Extracts in Alloxan-Induced Diabetic Rats  

PubMed Central

The present study was carried out to evaluate the antidiabetic activity of Vinca rosea methanolic whole plant extracts in alloxan induced diabetic rats for 14 days. The methanolic whole plant extract at high dose (500?mg/kg) exhibited significant anti-hyperglycemic activity than whole plant extract at low dose (300?mg/kg) in diabetic rats. The methanolic extracts also showed improvement in parameters like body weight and lipid profile as well as regeneration of ?-cells of pancreas in diabetic rats. Histopathological studies reinforce the healing of pancreas, by methanolic Vinca rosea extracts, as a possible mechanism of their antidiabetic activity.

Ahmed, Mohammed Fazil; Kazim, Syed Mohammed; Ghori, Syed Safiullah; Mehjabeen, Syeda Sughra; Ahmed, Shaik Rasheed; Ali, Shaik Mehboob; Ibrahim, Mohammed

2010-01-01

37

Effect of aqueous and ethanol extracts of Cassia auriculata L. flowers on diabetes using alloxan induced diabetic rats  

Microsoft Academic Search

In the present study the antidiabetic potential of aqueous and ethanol extract of Cassia auriculata L. flowers was assessed in alloxan-induced diabetic rats. The phytochemical screening and antioxidant activity were made in these extracts. Antidiabetic agents (Flavonoids and phenolic acids) and free radical scavenging activity in water-soluble fraction of the ethanol extract was higher compared to that of aqueous extract.

F Lukmanul Hakkim; S Girija; R Senthil Kumar

2007-01-01

38

Effect of sodium molybdate on the status of lipids, lipid peroxidation and antioxidant systems in alloxan-induced diabetic rats  

Microsoft Academic Search

Background: Diabetes mellitus manifests itself in a wide variety of complications and the symptoms of the disease are multi-factorial. Methods: The lipid peroxidation (LPO) and antioxidant status were investigated in hemolysate, liver and kidney in alloxan-induced diabetic rats and the effect of molybdate supplementation on antioxidant defense systems. Results: Diabetic rats exhibited an increase in the levels of lipids, lipid

Saraswathi R. Panneerselvam; Swaminathan Govindasamy

2004-01-01

39

Effects of Administration of Alpha-Melanocyte Stimulating Hormone (?-MSH) on Some Hematological Values of Alloxan-induced Diabetic Rats  

Microsoft Academic Search

This study was designed to evaluate the role of alpha- melanocyte stimulating hormone (?- MSH) on heart rate and some hematological values in alloxan induced diabetic rats. 40 male white rats were divided into four experimental groups: control, diabetic, ?-MSH-treated and ?-MSH-treated diabetic. At the end of the experimental period (3weeks), animals in all four groups were fasted for 12

Kamal Mohmoud Saleh Mansi; Saleh Mansi

2006-01-01

40

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

41

Biochemical study on the hypoglycaemic effects of extract and fraction of Acacia catechu willd in alloxan-induced diabetic rats  

Microsoft Academic Search

Various extracts including petroleum ether, chloroform, acetone, ethanol, aqueous and crude aqueous of barks of Acacia catechu (A. catechu) Willd (Leguminosae) and the two fractions of ethanolic extract were tested for antihyperglycaemic activity in glucose-loaded hyperglycaemic rats. The effective extract and fraction of A. catechu were subjected to anti- diabetic study in alloxan-induced diabetic rats at two dose levels, 200

Edwin Jarald; Siddheshwar B Joshi; Dharam C Jain

42

Giant mitochondria in pancreatic acinar cells of alloxan-induced diabetic rats.  

PubMed

This was a study of the microscopic, ultrastructural, immunohistochemical, and enzyme cytochemical features of giant eosinophilic granules encountered in pancreatic acinar cells of alloxan-induced diabetic rats. Seven male F344 rats with diabetes induced by a single i.v. dose of alloxan were sacrificed after twenty-five weeks of treatment. Histologically, the pancreatic acini were diffusely atrophied, and the islets showed marked atrophy or had disappeared, and giant eosinophilic granules and small vacuoles were observed in almost all acinar cells. The eosinophilic granules showed negative reactions for periodic acid-Schiff (PAS) and acid phosphatase, as well as fat stains such as Nile blue, Oil red O, and Sudan III. Ultrastructurally, the giant eosinophilic granules were huge structures surrounded by a double membrane containing many irregular cristae. A large amount of small lipid droplets was also apparent in the basal area of the acinar cells. Immunohistochemical analysis of prohibitin, a kind of protein located in the mitochondrial inner membrane, was partially positive in the marginal area of some giant eosinophilic granules, but negative for the central area. The enzyme activity for succinic dehydrogenase (SDH), one of the mitochondrial enzymes, showed a localizing pattern similar to that of prohibitin. These findings confirmed that the giant eosinophilic granules in the exocrine pancreas of alloxan-induced diabetic rats were giant mitochondria. PMID:20448086

Sano, Tomoya; Ozaki, Kiyokazu; Matsuura, Tetsuro; Narama, Isao

2010-05-06

43

Antidiabetic activity of ethanolic extract of tubers of Dioscorea alata in alloxan induced diabetic rats  

PubMed Central

Objective: To evaluate the antidiabetic activity of ethanolic extract of Dioscorea alata in glucose loaded and alloxan induced diabetic rats. Materials and Methods: The authenticated tubers of D. alata (DA) (JSSCPDP/2008/157) were collected from Dharmapuri, Tamil Nadu. The ethanol extract was tested for hypoglycemic activity in normal rats. In oral glucose tolerance test, glucose (3 g/kg, p.o.) was administered to non diabetic control, metformin (250 mg/kg, p.o.) and DA extract (100 and 200 mg/kg, p.o.) to treat treated rats. Diabetes mellitus was induced by alloxan monohydrate (120 mg/kg, i.p.) in physiological saline after overnight fasting for 18 hours. DA extract (100 and 200 mg/kg, p.o.) and standard drug metformin (250 mg/kg, p.o.) were administered to diabetic rats for 21 days. Fasting blood glucose level and changes in body weight were measured on days 0, 7, 14, and 21. At the end of 21st day, serum lipid profile, total protein, albumin, and creatinine were assessed. Results: In glucose loaded normal rats, the treatment with the extract of DA had shown a highly significant reduction (P < 0.001) in blood glucose levels at the doses of 100 and 200 mg/kg, respectively. The extract did not produce hypoglycemic activity at both the dose levels in normal, fasted rats. In alloxan induced diabetic rats, the body weight of the DA extract treated animals had shown a significant increase (P < 0.001) after 21 days treatment. The blood glucose level was reduced significantly by 47.48% and 52.09% after 21 days treatment at dose levels 100 and 200 mg/kg, respectively. Serum lipid levels, total protein, albumin, and creatinine were reversed toward near normal in treated rats as compared to diabetic control. Conclusion: The results indicate that ethanol extract of DA tubers possesses significant antidiabetic activity.

Maithili, V.; Dhanabal, S.P.; Mahendran, S.; Vadivelan, R.

2011-01-01

44

Alteration of electrophysiological function of isolated retina from alloxan-induced diabetic rats: Effect of treatment with Ginkgo biloba extract  

Microsoft Academic Search

In the first stage the authors highlight the functional impairments owing to diabetic retinopathy by performing experiments\\u000a on isolated retinas of alloxan-induced diabetic rats. After 1 mo evolution of diabetes, the electroretinograms (ERG) obtained\\u000a on isolated retinas had an amplitude on average 20% lower than the controls, whereas after 2 mo of diabetes, this decrease\\u000a in amplitude is around 60%.

Michel Doly; Pierre Braquet; Marie-Thérèse Droy; Brigitte Bonhomme; MARIE-MADELEINE RUCHOCIX; Gaston Meyniel

1988-01-01

45

Hypoglicemic effect of Leandra lacunosa in normal and alloxan-induced diabetic rats.  

PubMed

Leandra lacunosa, popularly known as "erva-do-jabuti", is used in Brazilian folkloric medicine for the treatment of diabetes mellitus. Based on this traditional indication, the aim of this work was to evaluate the hypoglycemic activity of the hydroalcoholic extract of L. lacunosa aerial parts (LLH) in normal and alloxan-induced diabetic rats. Chromatographic fractionation of LLH was also carried out by several techniques, affording isolation of the following major compounds: ursolic acid (1), kaempferol (2), luteolin (3), and quercetin (4). The oral administration of LLH (500 mg/kg) in normal rats caused a significant reduction of 24.7% (P<0.05) in the blood glucose levels after 2 h of treatment, while the administration of chlorpropamide (20 mg/kg, p.o.) led to a reduction of 40.2% (P<0.01). After oral administration of glucose (10 g/kg, p.o.), LLH (500 mg/kg, p.o.) significantly inhibited the increase in blood glucose levels compared with the negative control group. The oral treatment with LLH (500 mg/kg) in alloxan-induced diabetic rats significantly reduced the blood glucose levels in 47.8% after 4 h of treatment, while chlorpropamide resulted in a significant reduction of 71.7% in the 4th hour. Our results showed that LLH, displays hypoglycemic activity, which may be related to the effect of the major compounds identified in the crude extract. This study seems to provide biological evidence for the folkloric use of L. lacunosa in the treatment of diabetes mellitus. PMID:18538949

Cunha, W R; Arantes, G M; Ferreira, D S; Lucarini, R; Silva, M L A; Furtado, N A J C; da Silva Filho, A A; Crotti, A E M; Araújo, A R B

2008-06-06

46

Influence of selenium (antioxidant) on gliclazide induced hypoglycaemia\\/anti hyperglycaemia in normal\\/alloxan-induced diabetic rats  

Microsoft Academic Search

Oxidative stress is involved in diabetes mellitus and its complications. Since diabetes is a stress-related disorder, supplementation\\u000a with antioxidants may improve the condition. The purpose of this study is to know the effect of oral administration of selenium\\u000a on blood glucose and its influence on gliclazide induced hypoglycaemia\\/antihyperglycaemia in normal and alloxan-induced diabetic\\u000a rats. Albino rats of either sex were

S. Satyanarayana; J. Rajad Sekhar; K. Eswar Kumar; L. Bacchus Shannika; Bettaiya Rajanna; Sharada Rajanna

2006-01-01

47

Antidiabetic activity of hydro-ethanolic extracts of Nymphaea Stellata flowers in normal and alloxan induced diabetic rats  

Microsoft Academic Search

The antidiabetic effect of hydro-ethanolic extract (HEE) of Nymphaea stellata Willd flower was investigated in normal and alloxan-induced diabetic rats. In the present study, the animals were divided in to normal control, diabetic control, diabetic treated and control treated group (n = 6). Effect of oral administration of HEE (300 mg\\/kg) for 30 days on the level of blood glucose,

K. Rajagopal; K. Sasikala

2008-01-01

48

Functional beta cell regeneration in the islets of pancreas in alloxan induced diabetic rats by (-)-epicatechin.  

PubMed

(-)-Epicatechin (1), a naturally occurring flavonoid compound was found to have reversed the diabetogenic action of alloxan in albino rats (2). (-)-Epicatechin administration in doses of 30 mg/kg (i.p.) twice daily for 4-5 days in alloxan induced (150 mg/kg, i.p.) diabetic albino rats (either sex), has brought down the high blood sugar levels to normal values. Concurrent histological studies of the pancreas of these animals showed regeneration of the beta-cell population of the islets which were earlier necrosed by alloxan. Immunoreactive insulin (IRI) studies showed that the regenerated beta-cells of the islets of pancreas are functional in nature. PMID:6759833

Chakravarthy, B K; Gupta, S; Gode, K D

1982-12-13

49

Wound healing activity of Malva sylvestris and Punica granatum in alloxan-induced diabetic rats.  

PubMed

The flowers of Malva sylvestris Linn. (Malvaceae) and Punica granatum Linn. (Punicaceae) are important medicinal plants in Iranian traditional medicine (Unani) whose have been used as remedy against edema, bum, wound and for their carminative, antimicrobial and anti-inflammatory activities. The diethyl ether extract of M. sylvestris and P. granatum flowers were used to evaluate the wound healing activity at 200 mg/kg/day dose in alloxan-induced diabetic rats. Wounds were induced in Wister rats divided into six groups as following; Group I, normal rats were treated with simple ointment base. Group II, diabetic rats were treated with simple ointment base (control). Groups III and IV, diabetic rats were treated with simple ointment base containing of extracts (diabetic animals), Groups V, diabetic rats were treated with simple ointment base containing of mixed extracts (1:1), Group VI, diabetic rats received the standard drug (nitrofurazone). The efficacy of treatment was evaluated based on wound area relative and histopathological characteristics. The extract-treated diabetic animals showed significant reduction in the wound area when compared with control. Also, histological studies of the tissue obtained on days 9th and 18th from the extract-treated by extract of M. sylvestris showed increased well organized bands of collagen, more fibroblasts and few inflammatory cells. These findings demonstrate that extract of M. sylvestis effectively stimulates wound contraction as compared to control group and other groups. M. sylvestris accelerated wound healing in rats and thus supports its traditional use. PMID:20873419

Pirbalouti, Abdollah Ghasemi; Azizi, Shahrzad; Koohpayeh, Abed; Hamedi, Behzad

50

Comparison between ethanolic and aqueous extracts from Chinese juniper berries for hypoglycaemic and hypolipidemic effects in alloxan-induced diabetic rats  

Microsoft Academic Search

Aim of the studyHypoglycaemic and hypolipidemic properties of the ethanolic and aqueous extracts, respectively, from Chinese juniper (Juniperus chinensis L.) berries were investigated in alloxan-induced diabetic rats.

Jung Bong Ju; Ji Su Kim; Chang Won Choi; Hae Kyung Lee; Tae-Kyun Oh; Sei Chang Kim

2008-01-01

51

Effect of Punica granatum Linn. (flowers) on blood glucose level in normal and alloxan-induced diabetic rats  

Microsoft Academic Search

‘Gulnar farsi’, male abortive flowers of Punica granatum L., are used for the treatment of diabetes mellitus in Unani medicine. Oral administration of its aqueous-ethanolic (50%, v\\/v) extract led to significant blood glucose lowering effect in normal, glucose-fed hyperglycaemic and alloxan-induced diabetic rats. This effect of the extract was maximum at 400 mg\\/kg, b.w.

M. A Jafri; M Aslam; Kalim Javed; Surender Singh

2000-01-01

52

Nutritional and Hypoglycemic Effect of Fruit Pulp of Annona squamosa in Normal Healthy and Alloxan-Induced Diabetic Rabbits  

Microsoft Academic Search

Thenutritive 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.

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

2005-01-01

53

Hypoglycemic effect of Rehmannia glutinosa oligosaccharide in hyperglycemic and alloxan-induced diabetic rats and its mechanism  

Microsoft Academic Search

The hypoglycemic and anti-diabetic effect of Rehmannia glutinosa oligosaccharide (ROS) in glucose-induced hyperglycemic and alloxan-induced diabetic rats and its mechanism was investigated in this paper. It was found that pretreatment of ROS in normal rats with 100mg\\/kg for 3 days, i.p., induced a partial prevention of hyperglycemia caused by glucose (2g\\/kg, i.p.), while when hyperglycemia was induced in adrenalectomized (ADX)

Ruxue Zhang; Jinhuang Zhou; Zhengping Jia; Yongxiang Zhang; Guoming Gu

2004-01-01

54

Hypoglycaemic and Antidiabetic Activities of Seeds of Myristica fragrans in Normoglycaemic and Alloxan-induced Diabetic Rats  

Microsoft Academic Search

The present study was designed to investigate the hypoglycaemic and antidiabetic activity of seeds of Myristica fragrans in normoglycaemic and alloxan- induced diabetic rats. The petroleum ether (60-80º C) extract of Myristica fragrans (PEMF) was administered orally in normal fasted, glucose fed (1.5 g\\/kg, p.o.) and alloxan (120 mg\\/kg, s.c.)- induced diabetic rats (n=5). The blood glucose levels were estimated

R. S. Somani; A. K. Singhai

55

Effects of Artemisia pallens Wall. on blood glucose levels in normal and alloxan-induced diabetic rats  

Microsoft Academic Search

Oral administration of the methanol extract of the aerial parts of Artemisia pallens Wall. (used in Indian folk medicine for the treatment of diabetes mellitus) led to significant blood glucose lowering effect in glucose-fed hyperglycaemic and alloxan-induced diabetic rats. This effect of the extract was dose dependent and significant at 100 mg\\/kg level in glucose-fed rats. In fasted normal rats,

A. Subramoniam; P. Pushpangadan; S. Rajasekharan; D. A. Evans; P. G. Latha; R. Valsaraj

1996-01-01

56

Evaluation of hypoglycemic and antihyperglycemic effects of Datura metel (Linn.) seeds in normal and alloxan-induced diabetic rats  

Microsoft Academic Search

The seed powder of Datura metel was tested for its hypoglycemic activity in normal and alloxan-induced diabetic rats. Graded doses (25, 50 and 75mg\\/kg, p.o.) of the seed powder when given to both normal and diabetic rats produced significant reduction in blood glucose at the 8h. The effect was found to be dose dependent with all treatments at the doses

B Krishna Murthy; S Nammi; M. K Kota; R. V Krishna Rao; N Koteswara Rao; A Annapurna

2004-01-01

57

Effects of 18?-glycyrrhizin on the pharmacodynamics and pharmacokinetics of glibenclamide in alloxan-induced diabetic rats  

Microsoft Academic Search

This paper investigated the effects of 18?-glycyrrhizin (18?-GL) on the pharmacodynamics and pharmacokinetics of glibenclamide in experimental diabetic rats. 18?-GL (25 mg\\/kg) and\\/or glibenclamide (1 mg\\/kg) were given to alloxan-induced diabetic rats for consecutive 5 days. When the rats were co-treated with 18?-GL and glibenclamide, fasting plasma glucose concentration was further reduced, plasma insulin content and liver glycogen level were increased markedly as

Ying Ao; Jie Chen; Jiang Yue; Ren-Xiu Peng

2008-01-01

58

Hypoglycaemic and antihyperglycaemic effects of Trigonella foenum-graecum leaf in normal and alloxan induced diabetic rats.  

PubMed

The aqueous and alcoholic extracts of Trigonella foenum-graecum leaf were tested for hypoglycaemic activity in normal and alloxan-diabetic rats. Graded amounts (0.06, 0.2, 0.5, 1 g/kg, i.p. and 1, 2, 8 g/kg, p.o.) of the aqueous extract of Trigonella foenum-graecum leaf when given to both normal and alloxan-diabetic rats, a significant reduction of blood glucose concentration was noticed. On the other hand ethanolic extract of Trigonella foenum-graecum leaf produced no reduction in blood glucose concentration in normal rats but intra-peritoneal administration of 0.8 g/kg of the ethanolic leaf extract to diabetic rats produced a significant reduction of blood glucose concentration (p < 0.02) at 2 and 24 h only. Intraperitoneal and oral acute toxicity (LD50) and target organ effects were studied for the aqueous extract of Trigonella leaf in mice. LD50 of i.p. and oral administration were 1.9 and 10 g/kg respectively. The main organ affected after i.p. administration of the aqueous extract was the liver while oral administration of the aqueous extract of Trigonella did not produce any sign of organ damage. These results suggest that the aqueous extract of Trigonella foenum-graecum leaves given both orally and intraperitoneally possesses a hypoglycaemic effect in normoglycaemic and alloxan induced hyperglycaemic rats. PMID:9421250

Abdel-Barry, J A; Abdel-Hassan, I A; Al-Hakiem, M H

1997-11-01

59

Effect of silymarin on kidneys of rats suffering from alloxan-induced diabetes mellitus.  

PubMed

Oxidative stress contributes to the pathogenesis of diabetes mellitus and its sequelae nephropathy. The kidneys are especially prone to damage by free radicals. We therefore tested the effect of the flavonoid mixture silymarin, a free radical scavenger, on the activity and gene expression of superoxide dismutase, glutathione peroxidase and catalase, as well as on renal tissue morphology in rats with alloxan-induced diabetes mellitus. Alloxan-intoxicated rats were treated with silymarin 20 days after alloxan administration for 9 weeks. Alloxan-induced tissue damage and decreased the activity of the three enzymes, SOD (U/mg prot.): 14.4±1.75 vs 112±6.45 control, p<0.05, n=6; GSHPx (?M NADPH/min/mg prot.): 0.02±0.002 vs 0.121±0.01 control, p<0.05, n=6; CAT (k/seg/mg prot.): 0.022±0.003 vs 0.044±0.002 control, p<0.05, n=6. Silymarin treatment prevented tissue damage and restored the activity (SOD: 110.7±12.9U/mg prot.; GSHPx: 0.329±0.031 ?M NADPH/min/mg prot.; CAT: 0.054±0.002 k/seg/mg prot., n=6) and gene expression of the three antioxidant enzymes after 20 days of alloxan administration (SOD: 12.00±0.57 control, 9.00±0.1 diabetic p<0.05, 11.00±0.20 silymarin treated; GSHPx: 6.01±0.78 control, 9.03±0.3 diabetic p<0.05, 7.02±0.07 silymarin treated; CAT: 9.03±1.07 control, 12.02±0.60 diabetic p<0.05, 8.06±0.31 silymarin treated, n=6). It is suggested in this study that recuperative effect of silymarin on the renal tissue damage induced by alloxan may be related to an increase in the activity and recovery of gene expression of antioxidant enzymes which in addition to the glutathione system constitute some of the most important defense mechanisms against free radicals damage. As these results show, silymarin may be considered potentially in the treatment of diabetic nephropathy. PMID:20579862

Soto, C; Pérez, J; García, V; Uría, E; Vadillo, M; Raya, L

2010-06-25

60

Quantification of an apoprotein of pulmonary surfactant in normal and alloxan-induced diabetic rats by electroimmunoassay  

Microsoft Academic Search

We have quantitated a specific apoprotein of rat pulmonary surfactant using an electroimmunoassay and have examined its content\\u000a in the lungs of alloxan-induced diabetic rats. Rat lung surfactant was purified and was used to raise antisera in rabbits.\\u000a Antibodies against rat serum proteins were removed from the IgG fraction of the antiserum by means of affinity chromatography\\u000a using rat serum-linked

K. Sugahara; H. Maedah; K.-I. Yamashiro; H. Kohda; T. Okazaki; T. Morioka

1983-01-01

61

Hypoglycaemic effect of comatin, an antidiabetic substance separated from Coprinus comatus broth, on alloxan-induced-diabetic rats  

Microsoft Academic Search

Comatin, an inhibitor of the non-enzymatic glycosylation (NEG) reaction, was isolated from Coprinus comatus fermentation broth by macroporous resin separation, followed by chromatographic purification using a C18 reversed-phase column. The compound was identified as 4,5-dihydroxy-2-methoxy-benzaldehyde by high-resolution MS, IR, NMR and UV analyses. The hypoglycaemic effect of comatin, on both normal and alloxan-induced-diabetic rats, was investigated in the paper. The

Zhongyang Ding; Yingjian Lu; Zhaoxin Lu; Fengxia Lv; Yuhong Wang; Xiaomei Bie; Feng Wang; Kechang Zhang

2010-01-01

62

Antidiabetic Effects of the Different Fractions of Ethanolic Extracts of Ocimum sanctum in Normal and Alloxan Induced Diabetic Rats  

Microsoft Academic Search

The antidiabetic effects of Ethyl acetate (Et-Ac), Petroleum-ether (Pet-ether), and Chloroform fractions from ethanolic extract of the leaves of Ocimum sanctum were investigated in normal and alloxan induced diabetic rats (AIDRs). The effect of these fractions (200 mg\\/kg body weight i.p) on fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), serum glutamate oxaloacetate transaminases, serum glutamate pyruvate transaminases (SGOT,

M. R. I. Khan; M. A. Islam; M. S. Hossain; M. Asadujjaman; M. I. I. Wahed; B. M. Rahman; A. S. M Anisuzzaman; S. M. Shaheen; Maruf Ahmed

2010-01-01

63

Antidiabetic properties of ethanolic extract of Cnidoscolus aconitifolius on alloxan induced diabetes mellitus in rats.  

PubMed

This research was designed to investigate the antidiabetic properties of ethanolic extract of Cnidoscolus aconitifolius in alloxan-induced diabetes mellitus in Wistar male albino rats. Thirty male albino rats were used. Diabetes mellitus was induced in five of the six groups (B-F) by a single intra-peritoneal injection at the dose of 100mg/kg after normal fasting blood glucose had been determined. Group A served as the positive control while groups C-E received 100mg/kg, 500mg/kg and 1000mg/kg of Cnidoscolus aconitifolius extract respectively. Group B did not received any treatment while group F received chlorpropamide, a standard drug used in the treatment of diabetes mellitus. Blood glucose and body weights were monitored weekly for four weeks. Plasma lipids and electrolytes such as Total cholesterol, Triglyceride, Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL), Creatinine and Blood Urea Nitrogen (BUN) were determined after four weeks of treatment with Cnidoscolus aconitifolius extract. The results show significant reduction (P<0.001) in the blood glucose in group C (100mg/kg of Cnidoscolus aconitifolius) when compared with diabetic control (Alloxan only) and other treatment groups. There was gradual increase in weight of all treatment groups compared with the diabetic control, which had progressive weight loss. Plasma cholesterol levels also significantly reduced (P<0.001) in rats treated with 1,000mg/kg Cnidoscolus aconitifolius extract. From this study, Cnidoscolus aconitifolius extract was found to considerably reduce blood glucose and plasma cholesterol levels and progressively increase weight gain in diabetic treated rats confirming its traditional use for the treatment of diabetes. PMID:22416660

Oyagbemi, A A; Odetola, A A; Azeez, O I

2010-12-01

64

Efectos antidiabéticos de liposomas cargados con glibenclamida en ratas con diabetes inducida por alloxan Antidiabetic Activity of Glibenclamide Loaded Liposomes in Alloxan Induced Diabetic Rats  

Microsoft Academic Search

The antidiabetic activity of Glibenclamide loaded liposomes was investigated in model of alloxan-induced diabetes in rats. The blood glucose level was measured at 0 h and 1, 2, 4, 6, 8, 10, 12, 14 and 16h after the treatment. The alloxan - diabetic rats showed signifi cant reduction in blood glucose level, after treatment with Glibenclamide loaded liposomes and orally

SINGH M; GUPTA A; YADAV S; RAMASAMY M

65

Alterations in beta-islets of Langerhans in alloxan-induced diabetic rats by marine Spirulina platensis.  

PubMed

Marine Spirulina platensis may potentially influence the metabolic process in animal cells, and the effect of marine Spirulina platensis in normal and alloxan-induced diabetic rats was therefore investigated. Normal and diabetic rats (albino Wistar strain) were orally administered marine Spirulina platensis for 30 days and their blood levels of glucose and insulin and body weight changes were determined. Pancreatic histopathology was also noted. Treatment with marine Spirulina platensis caused significant alterations in the content of these indicators and therefore in the antidiabetic capacity of the treated animals compared to control rats. PMID:19912059

Muthuraman, P; Senthilkumar, R; Srikumar, K

2009-12-01

66

Antihyperglycemic effect of a new thiazolidinedione analogue and its role in ameliorating oxidative stress in alloxan-induced diabetic rats  

Microsoft Academic Search

Thiazolidinediones (TZDs) are a new class of antidiabetic drugs, having an insulin sensitizing effect in patients with type 2 diabetes. The contribution of oxidative stress from the standpoint of lipid and protein damage, alteration in endogenous antioxidant enzymes and effects of newly synthesized compounds, 5-[4-2-(6,7-Dimethyl-1,2,3,4-tetrahydro-2-oxo-4-quinoxalinyl)ethoxy]phenyl]methylene]thiazolid- ine-2,4-dione, (C1) in normal\\/alloxan-induced diabetic rats form the focus area of this study. Its effect

Jyoti Chaudhry; Narendra Nath Ghosh; Kapil Roy; Ramesh Chandra

2007-01-01

67

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.

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

2008-01-01

68

Action of capparis decidua against alloxan-induced oxidative stress and diabetes in rat tissues.  

PubMed

Alloxan-induced diabetic rats were treated with insulin (i.p.) or with Capparis decidua powder as a hypoglycaemic agent mixed with diet. The effect was assessed on lipid peroxidation (LPO) and the antioxidant defense system in rat tissues. The increased levels of blood glucose in diabetes produce superoxide anions and hydroxyl radicals in the presence of transition metal ions which cause oxidative damage to cell membranes. The heart tissue showed an increased lipid peroxidation (LPO) in diabetic rats while no significant change was observed in the liver and kidney. The treatment with C. decidua lowered LPO in these tissues even more effectively than insulin-treated rats. The superoxide dismutase (SOD) activity increased in the heart and kidneys in the diabetic group of rats probably to increase dismutation of superoxide anions. However, treatment with C. decidua decreased SOD activity in the liver and kidney and was comparable to control rats. Catalase (CAT) activity was not significantly affected in any of the tissues in diabetic and insulin-treated animals, however, CAT activity markedly increased in tissues with C. decidua treatment. Total and Se-dependent glutathione peroxidase (GSH-Px) in the heart was markedly lowered in diabetic rats which recovered with insulin as well as with C. decidua treatment. The increase in GSH-Px and CAT activity with C. decidua treatment may lower H2O2 toxicity and reduce oxidative stress in diabetes. However, glutathione (GSH) content in the heart and kidney and glutathione reductase (GSH-R) activity in all the tissues studied increased in diabetic rats while treatment with insulin lowered GSH content and GSH-R activity in these tissues. The treatment with C. decidua also decreased GSH-R activity in the kidney and heart which resulted in the decrease in GSH content in these tissues. The changes such as the increase in kidney and heart SOD may be an adaptive response in order to neutralize superoxide anions. The increase in GSH content and GSH-R activity in the tissue are in response to neutralize superoxide anions and to counteract oxidative stress in diabetes. Glutathione S-transferase (GST) was not significantly affected in diabetic rat tissue, however, heart GST increased with antidiabetic treatments. The increase in glucose-6-phosphate dehydrogenase (G6PDH) in the kidney and heart of diabetic rats subsequently decreased with C. decidua treatment. The increase in G6PDH in tissues may increase NADPH generation required for GSH-R activity and GSH production. It is suggested that these changes initially counteract the oxidative stress in diabetes, however, a gradual decrease in the antioxidative process may be one of the factors which results in chronic diabetes. The data indicate that C. decidua may have potential use as an antidiabetic agent and in lowering oxidative stress in diabetes. PMID:9367667

Yadav, P; Sarkar, S; Bhatnagar, D

1997-09-01

69

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

70

Long-Term Effects of Insulin Therapy, Islet Transplantation, and Pancreas Transplantation in the Prevention of Glomerular Changes in Kidneys of Alloxan-Induced Diabetic Rats  

Microsoft Academic Search

Groups of inbred alloxan-induced diabetic rats were treated with insulin (I), islets (IT), or pancreas transplantation (PT). Nondiabetic (N) and untreated diabetic (D) control groups were concurrently included. Each group was divided into five subgroups of 10 rats and killed after follow-up of 1, 3, 6, 9, and 12 months. Clinical and laboratory parameters were recorded, and kidney ultrastructural and

C. T. Spadella; M. M. Lerco; J. L. M. Machado; C. S. Macedo

2005-01-01

71

Insulin-like antigen of mangrove leaves and its anti-diabetic activity in alloxan-induced diabetic rats.  

PubMed

The objective of this study was to evaluate the anti-diabetic potential of three mangrove plants, Rhizophora mucronata, Rhizophora apiculata and Rhizophora annamalayana, and to detect the presence of their insulin-like protein. The in vivo anti-diabetic experiment was done on male albino Wister rats. Oral administration of 60?mg?kg(-1) leaf powder extract of the three different mangrove plants for 30 days modulated the parameters such as blood glucose, plasma insulin, body weight, total haemoglobin, glycosylated haemoglobin, liver glycogen, plasma and tissue lipids, cholesterol, triglycerides, free fatty acids and phospholipids to normal levels in the alloxan-induced diabetic rats. The anti-diabetic activity of R. apiculata was more pronounced than that of the other mangrove extracts, but it was on a par with the commercial drug glibenclamide. The presence of an insulin-like protein in the mangrove extracts was detected by SDS-PAGE analysis and confirmed through ELISA. Hence, the anti-diabetic activity and the presence of an insulin-like protein in Rhizophora species were proved scientifically. PMID:22017188

Alikunhi, Nabeel M; Kandasamy, Kathiresan; Manoharan, Chinthamani; Subramanian, Manivannan

2011-10-24

72

Paradoxical effects of a selective cyclooxygenase-2 inhibitor, etodolac, on proliferative changes of forestomach in alloxan-induced diabetic rats.  

PubMed

A single intravenous injection of alloxan, a non-genotoxic diabetogenic chemical, induces proliferative changes in forestomach mucosa of rats, and some lesions progress to squamous cell carcinoma accompanied with inflammatory change. The present study was conducted to examine the effects of a selective cyclooxygenase-2 (COX-2) inhibitor, etodolac, on the proliferative changes of forestomach mucosa in alloxan-induced diabetic rats. Alloxan-induced diabetic rats were fed a diet containing 0.01% etodolac (AL+Et group) and standard diet (AL group). They were sacrificed after 25 and 50 weeks of feeding, respectively. Squamous cell hyperplasia of forestomach was completely suppressed by etodolac after 25 weeks. After 50 weeks of treatment, the proliferative changes in forestomach developed in all rats of the AL+Et group, but in only 55.6% of the rats in the AL group. The severity of proliferative lesions was much enhanced in the AL+Et group compared to the AL group, and was parallel to the inflammatory changes in individual cases. Ulceration and erosion were more severe in the AL+Et group. These findings demonstrate that etodolac suppresses proliferative and inflammatory changes with COX-2 expression of forestomach in the early stage, but enhances them after 50 weeks. PMID:19081232

Sano, Tomoya; Ozaki, Kiyokazu; Kodama, Yasushi; Matsuura, Tetsuro; Narama, Isao

2008-12-09

73

Effect of Ginger Extract Consumption on levels of blood Glucose, Lipid Profile and Kidney Functions in Alloxan Induced-Diabetic Rats  

Microsoft Academic Search

In recent years, ginger has become a subject of interest because of its beneficial effects on human health. The purpose of the present study was to investigate the effects of daily oral administration of ginger extract for 6 weeks on plasma glucose, lipid profile and kidney functions in alloxan -induced diabetic rats to show the ameliorating and partly curative effects

Abd-Elraheem A. Elshater; Muhammad M. A. Salman; Mahrous M. A. Moussa

74

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.

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

2010-01-01

75

EFFECT OF AQUEOUS EXTRACTS OF ALLIGATOR PEAR SEED (PERSEA AMERICANA MILL) ON BLOOD GLUCOSE AND HISTOPATHOLOGY OF PANCREAS IN ALLOXAN-INDUCED DIABETIC RATS  

Microsoft Academic Search

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 300mg and 600mg\\/kg body weight of alligator pear seed extract. Two non-diabetic groups were also administered with 300mg and 600mg\\/kg body weight

DO EDEM; PE EBONG

76

Anti-diabetic effect of camel milk in alloxan-induced diabetic dogs: a dose-response experiment.  

PubMed

This study was conducted to evaluate the effect of camel milk in alloxan-induced diabetic dogs and to follow this effect at three doses of milk. Firstly, three groups of dogs were used: two groups composed each of four diabetic dogs and receiving raw camel milk (treatment 1) or cow milk (treatment 2), and four healthy dogs getting raw camel milk (treatment 3) were used as control. Each animal was treated with 500 ml of milk daily. Secondly, we compared the effects of three amounts of camel milk: 100 ml, 250 ml and 500 ml to treat the diabetic dogs. After week 3, the dogs treated with camel milk showed a statistically significant decrease in blood glucose (from 10.88 +/- 0.55 to 6.22 +/- 0.5 mmol/l) and total protein concentrations (from 78.16 +/- 2.61 g/l to 63.63 +/- 4.43 g/l). For cholesterol levels, there was a decrease from week 2 (from 6.17 +/- 0.5 mmol/l to 4.79 +/- 0.5 mmol/l). There were no significant difference in blood glucose, cholesterol or total protein concentrations in dogs drinking 250 and 500 ml of camel milk. The dogs treated with 100 ml of camel milk did not show any significant decrease in blood glucose levels, and cholesterol and total protein concentrations. The investigation was not limited to the improvement in glycemic balance, lipids and proteins control in diabetic dogs getting camel milk, but we also noted a stability of this state after the dogs stopped to drink milk. This effect depended on the quantity of camel milk used to treat diabetic dogs. PMID:19906135

Sboui, A; Khorchani, T; Djegham, M; Agrebi, A; Elhatmi, H; Belhadj, O

2009-11-11

77

Hypoglycemic and antidiabetic activities on the stem bark aqueous and ethanol extracts of Musanga cecropioides in normal and alloxan-induced diabetic rats  

Microsoft Academic Search

Daily oral administration of the aqueous and ethanolic extracts of Musanga cecropioides stem bark in normal and diabetic rats at doses of 250, 500 and 1000 mg\\/kg\\/day , for 14 days significantly lowered the fasting plasma glucose levels in normal and alloxan-induced diabetic rats in dose-dependent fashion. The ethanol extract induced more significant antidiabetic effect than the aqueous extract.

A. A. Adeneye; O. P. Ajagbonna; O. W. Ayodele

2007-01-01

78

EFFECTS OF Artemisia sieberi Besser (A. herba-alba) ON HEART RATE AND SOME HEMATOLOGICAL VALUES IN NORMAL AND ALLOXAN-INDUCED DIABETIC RATS  

Microsoft Academic Search

The present study was designed to evaluate the effects of oral administration of Artemisia sieberi Besser on heart rate and some hematological values in normal and alloxan-induced diabetic rats. It was found that water extract of Artemisia sieberi produced significant (p<0.05) reduction in blood glucose level in diabetic rats after 10 days of treatment; however, there was a significant (p<0.05)

Kamal Mansi; Jamil Lahham

79

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

80

Influence of selenium (antioxidant) on gliclazide induced hypoglycaemia/anti hyperglycaemia in normal/alloxan-induced diabetic rats.  

PubMed

Oxidative stress is involved in diabetes mellitus and its complications. Since diabetes is a stress-related disorder, supplementation with antioxidants may improve the condition. The purpose of this study is to know the effect of oral administration of selenium on blood glucose and its influence on gliclazide induced hypoglycaemia/antihyperglycaemia in normal and alloxan-induced diabetic rats. Albino rats of either sex were divided into three groups of six each. Group-I/II/III were treated with selenium 1/2 TD (0.9 microg/200 g rat)/TD (1.8 microg/200 g rat)/2TD (3.6 microg/200 g rat), respectively. Later group II was treated with gliclazide TD (1.44 mg/200 g rat)/selenium TD + gliclazide TD with a washout period of 1 week between the treatments. Diabetes was induced by alloxan monohydrate 100 mg/kg body weight i.p. A group of six rats showing fasting blood glucose levels ranging from 175-250 mg/dl were selected for the study. Rats were treated with selenium TD, gliclazide TD and selenium TD + gliclazide TD with a washout period of 1 week between the treatments. Selenium 1/2 TD and TD produced hypoglycaemia while 2TD produced hyperglycaemia. The combination of selenium TD with gliclazide TD, significantly enhanced the glucose lowering effect of gliclazide in normal and diabetic rats. PMID:16444594

Satyanarayana, S; Sekhar, J Rajad; Kumar, K Eswar; Shannika, L Bacchus; Rajanna, Bettaiya; Rajanna, Sharada

2006-02-01

81

The Protective Effect of Cordymin, a Peptide Purified from the Medicinal Mushroom Cordyceps sinensis, on Diabetic Osteopenia in Alloxan-Induced Diabetic Rats  

PubMed Central

The aim of this study was to investigate the protective effect of cordymin on diabetic osteopenia in alloxan-induced diabetic rats and the possible mechanisms involved. The diabetic rats received daily intraperitoneal injection with cordymin (20, 50, and 100?mg/kg/day) for 5 weeks. Cordymin could restore the circulating blood glucose, glycosylated hemoglobin (HbA1c), serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), and insulin levels in a dose-dependent manner. Also, the treatment of diabetic rats with cordymin could partially reverse the ? cells death and decrease the total antioxidant status (TAOS) in the diabetic rats. The results may directly and indirectly account for the possible mechanism of the beneficial effect of cordymin on diabetic osteopenia, which was confirmed with the increased bone mineral content (BMC) and bone mineral density (BMD) in diabetic rats (P < 0.05). All those findings indicate that cordymin may play a protective role in diabetic osteoporosis.

Qi, Wei; Zhang, Yang; Yan, Ya-bo; Lei, Wei; Wu, Zi-xiang; Liu, Ning; Liu, Shuai; Shi, Lei; Fan, Yong

2013-01-01

82

Therapeutic effect of phytoecdysteroids rich extract from Ajuga iva on alloxan induced diabetic rats liver, kidney and pancreas.  

PubMed

In the current study, the effect of Ajuga iva extract on blood glucose, lipid profile, hepatic and renal toxicity and antioxidant enzyme activities in alloxan-induced diabetic rats was investigated. Diabetes was confirmed by measuring the glucoserua concentration 15 days after alloxan administration. Ajuga iva extract was administrated orally 3 weeks after alloxan injection. Our results investigate that Ajuga iva extract supplementation increased the levels of both enzymatic antioxidant (superoxide dismutase, catalase and glutathione peroxidase) and metals antioxidants (iron, copper, magnesium, calcium) and decreased lipid peroxidation level (TBARs). Besides Ajuga iva ameliorated diabetes provoked hepatic and renal toxicity appeared by a lower level in total and direct bilirubin, urea, creatinine, triglyceride (TG), cholesterol and a higher level in HDL-cholesterol. Besides, the activities of phosphatase alkalines (PAL), aspartate and lactate transaminase (AST & ALT) were decreased. The benefices effects of phytoecdysteroids of Ajuga iva confirmed by histological observation in pancreatic tissues. In conclusion, Ajuga iva phytoecdysteroids supplements seem to be beneficial for correcting the hyperglycemia and preventing diabetic complications in liver, pancreas and kidneys. PMID:19478420

Hamden, Khaled; Ayadi, Fatma; Jamoussi, Kamel; Masmoudi, Hatem; Elfeki, Abdelfattah

2008-01-01

83

Protective influence of vitamin E on the antioxidant defence system in the whole blood and liver of normal and alloxan-induced diabetic rats  

Microsoft Academic Search

The effect of oral administration of vitamin E for twenty-eight consecutive days on blood glucose, reduced glutathione levels,\\u000a antioxidant enzymes (superoxide dismutase and catalase activities), and levels of malondialdehyde (as an index of free radical-mediated\\u000a lipid peroxidation) was observed in the whole blood and liver of normal and alloxan-induced diabetic rats. It was found that\\u000a oral administration of vitamin E

J. O. Olanlokun

2008-01-01

84

Maternal zinc intake of Wistar rats has a protective effect in the alloxan-induced diabetic offspring.  

PubMed

Zinc has a role in the synthesis, storage, and secretion of insulin, and has been suggested to be beneficial when used in the diabetic state. Effect of zinc intake in pregnant rats has been studied here on diabetized offspring. Pregnant rats were divided in two groups; the control group received normal food and water, and the experimental group received zinc sulfate during pregnancy and 3 weeks after offspring birth. Male offspring from the control (C) and experimental (E) groups were divided each in three groups: C1, fed with normal food and water; C2, diabetized with alloxan; C3, received zinc sulfate; E1, fed with normal food and water; E2, diabetized with alloxan; and E3, receiving zinc sulfate. After 30 days, the histological changes of pancreatic tissues were investigated by light microscopy. Body weight, blood glucose, serum insulin levels, food intake, water intake, and urine quantity were also compared between the groups. Water intake and urine quantity were decreased significantly (p?diabetic group) in comparison with C2 (control diabetic group), but there was no significant difference in the body weight in C2 in comparison with E2, while blood glucose was decreased significantly (p?alloxan-induced beta-cell degeneration. In conclusion, this work showed that maternal zinc intake may influence subsequent deleterious effects of diabetes on alloxan-diabetized offspring. PMID:22730079

Yaghmaei, Parichehreh; Esfahani-Nejad, Hamideh; Ahmadi, Ramesh; Hayati-Roodbari, Nasim; Ebrahim-Habibi, Azadeh

2012-06-23

85

Hypoglycemic and hypolipidemic effects of protein hydrolysates from zebra blenny (Salaria basilisca) in alloxan-induced diabetic rats.  

PubMed

The present study investigates the hypoglycemic and hypolipidemic effects of protein hydrolysates obtained from zebra blenny (Salaria basilisca) muscles treated with three different crude alkaline protease extracts in alloxan-induced diabetic rats (AIDR). Analysis of amino acid composition revealed that zebra blenny protein hydrolysates (ZBPHs) were valuable sources of essential amino acids and rich in leucine, which is one of the active ingredients for blood glucose control by inducing insulin release in both rats and humans. Treatment of AIDR with ZBPHs revealed a significant inhibition of ?-amylase activity in serum and the intestine, as well as a reduction of blood glucose and glycated hemoglobin (HbA1c) levels in diabetic rats. Further, ZBPHs also decreased significantly the triglyceride (TG), total-cholesterol (TC) and LDL-cholesterol (LDL-c) levels in the serum and liver of diabetic rats, while they increased the HDL-cholesterol (HDL-c) level, which helped to maintain the homeostasis of blood lipids. Furthermore, ZBPHs exhibited potent protective effects against heart attack markers by reversing myocardial enzyme serum back to normal levels. ZBPHs may also exert significant protective effects on liver function, evidenced by a marked decrease in the level of serum bilirubin as well as in the activities of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GGT). These beneficial effects of ZBPHs were confirmed by histological findings in the hepatic and pancreatic tissues of diabetic rats. Indeed, they avoid lipid accumulation in the hepatocytes and protect the pancreatic ?-cells from degeneration. Overall, the findings of the current study indicate that ZBPHs significantly attenuated hyperglycemia and hyperlipidemia in AIDR. PMID:24104463

Ktari, Naourez; Mnafgui, Kais; Nasri, Rim; Hamden, Khaled; Bkhairia, Intidhar; Ben Hadj, Aïda; Boudaouara, Tahia; Elfeki, Abdelfattah; Nasri, Moncef

2013-10-24

86

Oxidative Stress and the Role of Cumin (Cuminum cyminum Linn.) in Alloxan-Induced Diabetic Rats  

Microsoft Academic Search

The effect of cumin (Cuminum cyminum Linn.) on tissue lipid peroxidation and antioxidants in experimental diabetes mellitus was evaluated. Albino rats, non-diabetic and diabetic [those injected with alloxan monohydrate (150 mg kg body weight) intraperitoneally to induce diabetes mellitus, blood glucose in the range of 200–300 mg dl, were used in the study. Cumin (0.25 g kg body weight in

Dhandapani Surya; Ramasamy Subramanian Vijayakumar; Namasivayam Nalini

2005-01-01

87

Antidiabetic and antihyperlipidaemic effect of alcoholic Syzigium cumini seeds in alloxan induced diabetic albino rats  

Microsoft Academic Search

Syzigium cumini, commonly known as ‘jamun’, is widely used in different parts of India for the treatment of diabetes mellitus. The present study was designed to evaluate the antidiabetic and antihyperlipidaemic effect of an alcoholic extract of Syzigium cumini seeds (JSEt) in alloxan diabetic rats. Diabetes was induced by single intraperitoneal injection of alloxan (150mgkg?1 body weight). Oral administration of

P. Stanely Mainzen Prince; N. Kamalakkannan; Venugopal P. Menon

2004-01-01

88

ANTIDIABETIC AND HYPOLIPIDEMIC EFFECTS OF LAPORTEA OVALIFOLIA (URTICACEAE) IN ALLOXAN INDUCED DIABETIC RATS  

Microsoft Academic Search

Laportea ovalifolia (Scham and Thonn) is widly use in Cameroon for the treatment of diabetes mellitus. The present study was designed to evaluate the antidiabetic and hypolipidaemic effects of aqueous extract of Laportea ovalifolia aerial part in normal and alloxan diabetic rats. Diabetes was induced by intraperitoneal injection of alloxan (150 mg kg -1 body weight). The treatment was given

Claudia E. N. MOMO; E. OBEN

89

Heart rhythm disturbances in the neonatal alloxan-induced diabetic rat  

Microsoft Academic Search

Diabetic patients show a higher incidence of cardiac arrhythmias, including ventricular fibrillation and sudden death. Their electrocardiograms may show several alterations from normal patterns, many of them related to the QT. Various diastolic and systolic abnormalities are frequently reported in diabetic patients, and the severity of the abnormalities depend on the patients’ age and the duration of diabetes. The aim

Frank Christopher Howarth; Mohamed Shafiullah; Ernest Adeghate; Milos Ljubisavljevic; Michael Jacobson

2011-01-01

90

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

91

Glycated low density lipoprotein catabolism is increased in rabbits with alloxan-induced diabetes mellitus  

Microsoft Academic Search

Summary  Hyperglycaemia in diabetes mellitus is responsible for the process of non-enzymatic glycosylation of different proteins. Since we did not find elevated glycated apolipoprotein B levels in diabetic patients, an altered glycated apolipoprotein B metabolism was suspected in diabetic patients. Experiments in normal rabbits showed that non-reductive (in vitro) glycated low density lipoprotein (gly-LDL) was cleared at a slower rate than

W. Kortlandt; C. Benschop; H. J. M. van Rijn; D. W. Erkelens

1992-01-01

92

Effect of alloxan-induced diabetes on serum and cardiac butyrylcholinesterases in the rat  

Microsoft Academic Search

Elevated serum butyrylcholinesterase (BChE) activity in the diabetic rat, mouse and human is very evident. The source of the increased level of BChE in the diabetic condition is not known. The effect of diabetes on cardiac BChE has not been studied so far, in spite of high BChE levels in the heart. In the present study, we investigated the effect

K R Dave; S S Katyare

2002-01-01

93

Influence of streptozotocin- and alloxan-induced diabetes on the crosslinking of dermal collagen.  

PubMed

The influence of experimentally induced diabetes on rat dermal collagen crosslinking was investigated in male albino rats. In comparison to the normal, the diabetic group demonstrated decrease in percent reversibility of neutral salt-soluble collagen gel and susceptibility of insoluble collagen to denaturing agents and pronase whereas the aldehyde content was significantly increased. The electrophoretic gels revealed a marked decrease of alpha/beta ratio in diabetic animals. The results indicated that both the intra- and intermolecular crosslinkings of collagen were increased in experimentally induced diabetes. PMID:6216710

Mohanam, S; Bose, S M

94

Heart rhythm disturbances in the neonatal alloxan-induced diabetic rat.  

PubMed

Diabetic patients show a higher incidence of cardiac arrhythmias, including ventricular fibrillation and sudden death. Their electrocardiograms may show several alterations from normal patterns, many of them related to the QT. Various diastolic and systolic abnormalities are frequently reported in diabetic patients, and the severity of the abnormalities depend on the patients' age and the duration of diabetes. The aim of this experimental study has been to clarify the progressive effects on heart rhythm in neonatal alloxan (ALX) (induced at 5 days of age) diabetic male rats. Cardiac biopotential data were acquired in vivo with a biotelemetry system. After an overnight fast blood glucose in diabetic rats, compared to age-matched controls, was elevated before and at 60, 120 and 180min after a glucose challenge at 2 and 8 months of age. Heart rate and heart rate variability were modestly reduced and QT interval modestly prolonged in diabetic rats, compared to controls, at 2, 6 and 8 months of age. There was also an age-dependent decline in heart rate and prolongation in QT interval. At 8 months heart rate was 296±8bpm in diabetic compared to 311±10bpm in controls and heart rate variability was 27±3bpm in diabetic rats compared to 32±4bpm in controls. Physical activity was significantly reduced in diabetic rats, compared to controls, at 6 and 8 months of age. Body temperature was modestly reduced in diabetic rats, compared to controls, at 2, 6 and 8 months. In conclusion, the neonatal ALX-induced diabetes mellitus was associated with disturbances in heart rate, heart rate variability, QT interval which in turn may be associated with changes in physical activity and body temperature. PMID:21051208

Howarth, Frank Christopher; Shafiullah, Mohamed; Adeghate, Ernest; Ljubisavljevic, Milos; Jacobson, Michael

2010-11-03

95

Effect of aqueous extract of the leaves of Acalypha wilkesiana ‘Godseffiana’ Muell Arg (Euphorbiaceae) on the hematology, plasma biochemistry and ocular indices of oxidative stress in alloxan induced diabetic rats  

Microsoft Academic Search

Ethnopharmacological relevanceThe leaves of Acalypha wilkesiana are used in Southern Nigeria for the management of hypertension and diabetes mellitus. In this study, the effect of aqueous extract of the leaves of Acalypha wilkesiana on the hematology, plasma biochemistry and ocular indices of oxidative stress was investigated in alloxan induced diabetic rats.

Jude C. Ikewuchi; Eugene N. Onyeike; Augustine A. Uwakwe; Catherine C. Ikewuchi

2011-01-01

96

Antidiabetic activity of Terminalia pallida fruit in alloxan induced diabetic rats  

Microsoft Academic Search

Different doses of ethanolic fraction of fruits of Terminaliapallida were evaluated for hypoglycemic and antihyperglycemic activity in normal and alloxan diabetic rats. The oral administration of ethanolic extract at a dosage of 0.5g\\/kg body weight exhibited a significant antihyperglycemic activity in alloxan diabetic rats, whereas in normal rats no hypoglycemic activity was observed.

B. Kameswara Rao; P. Renuka Sudarshan; M. D. Rajasekhar; N. Nagaraju; Ch. Appa Rao

2003-01-01

97

Hypoglycaemic and other related actions of Tinospora cordifolia roots in alloxan-induced diabetic rats  

Microsoft Academic Search

Tinospora cordifolia is widely used in Indian Ayurvedic medicine for treating diabetes mellitus. Oral administration of an aqueous T. cordifolia root extract (TCREt) to alloxan diabetic rats caused a significant reduction in blood glucose and brain lipids. The extract caused an increase in body weight, total haemoglobin and hepatic hexokinase. The root extract also lowers hepatic glucose-6-phosphatase and serum acid

P. Stanely; Mainzen Prince; Venugopal P. Menon

2000-01-01

98

HYPOLIPIDEMIC EFFECT OF CUMINUM CYMINUM L. ON ALLOXAN-INDUCED DIABETIC RATS  

Microsoft Academic Search

Hyperlipidemia is an associated complication of diabetes mellitus. Many spices and herbs are known to be hypoglycaemic. Cuminum cyminum belonging to the family Apiaceae is widely used in Ayurvedic medicine for the treatment of dyspepsia, diarrhoea and jaundice.The present work was done to study the role of C. cyminum supplementation on the plasma and tissue lipids in alloxan diabetic rats.

SURYA DHANDAPANI; VIJAYAKUMAR RAMASAMY SUBRAMANIAN; SENTHILKUMAR RAJAGOPAL; NALINI NAMASIVAYAM

2002-01-01

99

Antidiabetic and antihyperlipidaemic effect of alcoholic Syzigium cumini seeds in alloxan induced diabetic albino rats.  

PubMed

Syzigium cumini, commonly known as 'jamun', is widely used in different parts of India for the treatment of diabetes mellitus. The present study was designed to evaluate the antidiabetic and antihyperlipidaemic effect of an alcoholic extract of Syzigium cumini seeds (JSEt) in alloxan diabetic rats. Diabetes was induced by single intraperitoneal injection of alloxan (150 mg kg(-1) body weight). Oral administration of alcoholic JSEt to diabetic rats at a dose of 100 mg kg(-1) body weight resulted in a significant reduction in blood glucose and urine sugar and lipids in serum and tissues in alloxan diabetic rats. The extract also increases total haemoglobin. The extract brought back all the parameters to normal levels. The effect of alcoholic JSEt was similar to that of insulin. Thus, our investigation clearly shows that alcoholic JSEt has both antidiabetic and antihyperlipidaemic effects. PMID:15120440

Prince, P Stanely Mainzen; Kamalakkannan, N; Menon, Venugopal P

2004-04-01

100

Influence of streptozotocin- and alloxan-induced diabetes on the crosslinking of dermal collagen  

Microsoft Academic Search

Summary  The influence of experimentally induced diabetes on rat dermal collagen crosslinking was investigated in male albino rats.\\u000a In comparison to the normal, the diabetic group demonstrated decrease in percent reversibility of neutral salt-soluble collagen\\u000a gel and susceptibility of insoluble collagen to denaturing agents and pronase whereas the aldehyde content was significantly\\u000a increased. The electrophoretic gels revealed a marked decrease of

Sanjeeva Mohanam; Sudha M. Bose

1982-01-01

101

Influence of streptozotocin and alloxan induced diabetes on the metabolism of dermal collagen in albino rats  

Microsoft Academic Search

Summary The metabolism of collagen in male rats made diabetic by treatment with either streptozotocin or alloxan was studied after the injection of3H-proline by estimating specific and total3H-hydroxyproline activity in skin collagen fractions and urine. Experimentally induced diabetes was found to decrease the neutral salt-soluble and acid-soluble collagen with no change in insoluble collagen as compared to a control group.

Sanjeeva Mohanam; Sudhamoy Bose

1981-01-01

102

Effect of sodium molybdate on carbohydrate metabolizing enzymes in alloxan-induced diabetic rats  

Microsoft Academic Search

We evaluated the effect of sodium molybdate on carbohydrate metabolizing enzymes and mitochondrial enzymes in diabetic rats. Diabetic rats showed a significant reduction in the activities of glucose metabolising enzymes like hexokinase, glucose-6-phosphate dehydrogenase, glycogen synthase and in the level of glycogen. An elevation in the activities of aldolase, glucose-6-phosphatase, fructose 1,6- bisphosphatase, glycogen phosphorylase and in the level of

R. Saraswathi Panneerselvam; Swaminathan Govindaswamy

2002-01-01

103

Antihyperglycemic activity of bacosine, a triterpene from Bacopa monnieri, in alloxan-induced diabetic rats.  

PubMed

This article describes the antihyperglycemic activity, in vivo antioxidant potential, effect on hemoglobin glycosylation, estimation of liver glycogen content, and in vitro peripheral glucose utilization of bacosine, a triterpene isolated from the ethyl acetate fraction (EAF) of the ethanolic extract of Bacopa monnieri. Bacosine produced a significant decrease in the blood glucose level when compared with the diabetic control rats both in the single administration as well as in the multiple administration study. It was observed that the compound reversed the weight loss of the diabetic rats, returning the values to near normal. Bacosine also prevented elevation of glycosylated hemoglobin in vitro with an IC?? value of 7.44 µg/mL, comparable with the one for the reference drug ?-tocopherol. Administration of bacosine and glibenclamide significantly decreased the levels of malondialdehyde (MDA), and increased the levels of reduced glutathione (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT) in the liver of diabetic rats. Bacosine increased glycogen content in the liver of diabetic rats and peripheral glucose utilization in the diaphragm of diabetic rats in vitro, which is comparable with the action of insulin. Thus, bacosine might have insulin-like activity and its antihyperglycemic effect might be due to an increase in peripheral glucose consumption as well as protection against oxidative damage in alloxanized diabetes. PMID:21154199

Ghosh, Tirtha; Maity, Tapan Kumar; Singh, Jagadish

2010-12-10

104

Parkinsonia aculeata aqueous extract fraction: biochemical studies in alloxan-induced diabetic rats.  

PubMed

The antidiabetic effect of Parkinsonia aculeata water soluble fraction (WSF) made of aerial parts of the plant (leaves and flowers) was investigated in alloxan diabetic rats. Its effect was compared with that of insulin (positive control). The physico-metabolic parameters measured were: body weight, food and liquid intake, urinary volume, hepatic glycogen, serum glucose, total cholesterol, HDL-cholesterol, triglycerides, urinary glucose and urea, and the weight of epididymal adipose tissue, liver, kidneys and the skeletal muscles (soleus and extensor digitorum longus). Oral administration of WSF (125 or 250 mg/kg) for 16 days exhibited a significant reduction in serum and urinary glucose, urinary urea, total cholesterol, HDL-cholesterol and triglycerides in alloxan diabetic rats. An improvement of hepatic glycogen, a decrease of liquid and food intake, and a significantly positive actions in the weight of skeletal muscles (soleus and extensor digitorum longus) and kidneys were also observed, but just diabetic group treated with WSF at a dose of 125 mg/kg showed significant reduction in urinary volume, body weight, an improvement of epididymal adipose tissue and a positive action in liver weight. The effects of WSF on the physico-metabolic parameters was comparable to those observed in diabetic insulin treated group. The results of this work suggest that P. aculeate may have new clinical significant choice in diabetes mellitus illness, and could explain the basis for its traditional use to manage diabetes-related complications by rural community of northeast of Brazil. PMID:17276638

Leite, A C R; Araújo, T G; Carvalho, B M; Silva, N H; Lima, V L M; Maia, M B S

2007-01-07

105

A study of hypoglycemic and antioxidant activity of Aegle marmelos in alloxan induced diabetic rats.  

PubMed

The present study was performed to evaluate the hypoglycemic and antioxidant effect of aqueous extract of Aegle marmelos leaves (AML) on diabetic rats. Male albino rats were randomly divided into three groups: Group I: Control; Group II: Diabetic rats; and Group III: Diabetic rats administered AML. Glucose, urea and glutathione-S-transferase (GST) in plasma, glutathione (GSH) and malondialdehyde (MDA) levels in erythrocytes were estimated in all the groups at the end of four weeks. There was a decrease in blood glucose at the end of four weeks in group III animals compared with group II, however it did not reach the control levels. There was an increase in erythrocyte GSH and a decrease in MDA in group III as compared to group II. The plasma GST levels were raised in diabetic rats when compared to controls. In the group III animals, there was a decrease in GST as compared to group II. Owing to hypoglycemic and antioxidant properties, AML may be useful in the long-term management of diabetes. PMID:15907058

Upadhya, Sharmila; Shanbhag, Kshama K; Suneetha, G; Balachandra Naidu, M; Upadhya, Subramanya

2004-10-01

106

Hepatic and pancreatic effects of polyenoylphosphatidylcholine in rats with alloxan-induced diabetes.  

PubMed

Polyenoylphosphatidylcholine (PPC: 100 or 300 mg kg-1 b.w., by gastric intubation for 30 days) produced a clearcut protection of the liver of rats treated with alloxan (150 mg kg-1 b.w., i.p.). The liver of rats treated with alloxan was characterized by hydropic dystrophy and lymphocytic infiltrations. Treatment with alloxan increased serum gamma-GT and ALAT activities. The liver structure of rats treated with PPC did not differ from the liver of control animals. PPC normalized the biochemical abnormalities caused by the diabetes. The number of pancreatic islets and beta/alpha cell ratio decreased in the diabetic rats. A number of beta-cells in this group did not contain granules. PPC prevented the decrease in the number of islets and the beta/alpha cell ratio in the pancreas of the diabetic rats. The intensity of staining of beta-cell granules in the pancreas of PPC-treated rats had a position intermediate between the control and diabetic groups. Alloxan increased the blood glucose content where treatment with PPC decreased this. The results suggest that PPC acts as a cytoprotector in the liver and pancreas of rats with experimental diabetes induced by alloxan. PMID:8640953

Buko, V; Lukivskaya, O; Nikitin, V; Tarasov, Y; Zavodnik, L; Borodinsky, A; Gorenshtein, B; Janz, B; Gundermann, K J; Schumacher, R

1996-06-01

107

Influence of streptozotocin and alloxan induced diabetes on the metabolism of dermal collagen in albino rats.  

PubMed

The metabolism of collagen in male rats made diabetic by treatment with either streptozotocin or alloxan was studied after the injection of 3H-proline by estimating specific and total 3H-hydroxyproline activity in skin collagen fractions and urine. Experimentally induced diabetes was found to decrease the neutral salt-soluble and acid-soluble collagen with no change in insoluble collagen as compared to a control group. The specific and total radioactivity of 3H-hydroxyproline in soluble and insoluble collagen fractions were also decreased. Studies of total 3H-hydroxyproline activities in soluble collagens and insoluble collagen showed that the conversion of soluble to insoluble collagen was influenced by diabetes. Both streptozotocin and alloxan were found to increase urinary excretion of total hydroxyproline and 3H-hydroxyproline during the first 12 h after the administration of 3H-proline. Weekly analyses of urinary hydroxyproline also indicated a similar pattern. The results of the present investigation clearly indicate decreased synthesis and increased catabolism of collagen accompanied by accelerated conversion of soluble to insoluble collagen in experimentally induced diabetes. PMID:6458190

Mohanam, S; Bose, S

108

Chronic Depression of Serum Sialic Acid Levels in Alloxan-Induced Diabetes.  

National Technical Information Service (NTIS)

The study was performed to determine whether alloxan treatment of rats alters levels of the terminal carbohydrate residues L-fucose and sialic acid of serum glyco-proteins. Results indicate that in the uncompensated diabetic animal a chronic depression of...

R. J. O. Woods P. Z. Sobocinski W. J. Canterbury N. S. Mathewson K. M. Hartley

1974-01-01

109

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.

Ananthakrishnan, Manikandan; Doss, Victor Arokia

2013-01-01

110

Nonenzymatic glycosylation reaction contributes to a rise of blood glucose in alloxan-induced diabetic rats  

Microsoft Academic Search

Non-enzymatic glycosylation reaction, which proceeded at an accelerated rate in diabetes, directly caused sharp diminution of total haemoglobin due to glycosylated proteins including haemoglobin digested by macrophages. The diminution contributed to hypoxia of tissue that repressed the enzymatic activities in the respiratory chain as well as in the tri-carboxylic acid cycle (TCA) and Embden-Meyerhof-Parnas (EMP) pathways. It was postulated that

Zhicai Zhang; Feng-Jie Cui

2007-01-01

111

Changes in Arachidonic Acid Metabolite Patterns in Alloxan-Induced Diabetic Rats  

Microsoft Academic Search

The vasodepressor responses to intravenous injections of arachidonic acid, and the formation of its metabolites, were studied in rats made diabetic 1 or 2 weeks after a 1-dose alloxan treatment. Arachidonic acid dose-dependently decreased the diastolic blood pressure in normal animals, but this hypotensive effect was significantly weaker in 2-week postalloxan-treated rats. Indometacin abolished arachidonic-acid-induced depressor responses in both normal

S.-C. G. Hui; C. W. Ogle; Z. Wang; Y. An; Y.-H. Hu

1989-01-01

112

Hypoglycaemic effect of Musa sapientum L. in alloxan-induced diabetic rats  

Microsoft Academic Search

Musa sapientum L. (‘Ney Poovan’) commonly known as ‘banana’ is mainly used in Indian folk medicine for the treatment of diabetes mellitus. Oral administration of 0.15, 0.20 and 0.25 g\\/kg of chloroform extract of the Musa sapientum flowers (MSFEt) for 30 days resulted in a significant reduction in blood glucose, glycosylated haemoglobin and an increase in total haemoglobin, but in

L Pari; J Uma Maheswari

1999-01-01

113

Good versus moderate regulation of alloxan-induced diabetes in arteriosclerotic and nonarteriosclerotic rats  

Microsoft Academic Search

Summary  Nonarteriosclerotic (virgin) and arteriosclerotic (breeder) rats were made diabetic with alloxan. Animals were treated with constantly adjusted doses of insulin, occasionally adjusted doses, or no treatment. The obese breeder rats lost weight; the lean virgin rats gained weight. All of the animals were autopsied 5 months post-alloxan. Blood pressure increased in virgin rats; the pre-existent mildly elevated blood pressure of

B. C. Wexler; D. G. Sangrey

1980-01-01

114

Effect of cadmium on antioxidant status in alloxane-induced diabetic rats.  

PubMed

Fifty-two healthy Swiss Male Albino rats aged two mo were used in this study. They were divided into four groups: control (C), diabetic (D), cadmium (Cd), and diabetic + Cd (D + Cd) groups. Diabetic condition was induced in D and D + Cd groups by administration of alloxane (5 mg/100 g). After this treatment, Cd and D + Cd groups were injected with CdCl2 i.p. (2 mg/kg/wk). At the end of the 2-mo experimental period, thiobarbituric acid reactive substances (TBARS), plasma and erythrocyte selenium (Se), plasma ceruloplasmin (Cp), and vitamin E (vit E) were determined in four groups of rats. The erythrocyte Se was lower in the experimental groups than in the controls. Plasma Se was significantly decreased in the D and D + Cd groups compared with the control group. Plasma Cp was unaltered. Plasma vit E was significantly decreased in Cd group in comparison with the C, D, and D+Cd groups. PMID:9282257

Gümü?lü, S; Yargiço?lu, P; A?ar, A; Edremitlio?lu, M; Alicigüzel, Y

1997-05-01

115

Hypoglycemic effect of Treculia africana Decne root bark in normal and alloxan-induced diabetic rats.  

PubMed

The solvent partitioned purified fractions of the hydro-acetone root bark extract of the African breadfruit (Treculia africana Decne) were evaluated for hypoglycemic activities in normal and diabetic albino rats. Fasting blood glucose levels were estimated by the use of a glucometer at pre-determined intervals after oral administration of the test extracts/fractions. Results revealed that the test fractions have only a slight effect on blood sugar level of normal rats. On short term and chronic administration in diabetic rats however, diethyl ether-soluble (DEF) and the water-soluble (WSF) fractions significantly reduced the fasting blood sugar levels (p<0.05) at differing rates when compared with the control group of animals. The diethyl ether soluble fraction (10 mg kg(-1) dose level) was found to exhibit the highest activity giving 69.4% reduction in blood sugar level (at 240 hours) which was in comparable range with the reference standard glibenclamide (0.5 mg kg(-1)) which reduced blood sugar levels by 65.8% below the initial baseline values. PMID:20161906

Oyelola, O O; Moody, J O; Odeniyi, M A; Fakeye, T O

2007-06-10

116

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

117

Blockade of the Formation of Insoluble Ubiquitinated Protein Aggregates by EGCG3"Me in the Alloxan-Induced Diabetic Kidney  

PubMed Central

Background Renal accumulation of reactive carbonyl compounds (RCCs) has been linked to the progression of diabetic nephropathy. We previously demonstrated that carbonyl stress induces the formation of amino-carbonyl cross-links and sharply increases the content of ?-sheet-rich structures, which is the seed of insoluble aggregates formation, and tea catechin (-)-epigallocatechin 3-gallate (EGCG) can reverse this process in vitro and in vivo. In this study, methylated derivative (-)-epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3”Me) was hypothesized to neutralize carbonyl stress mediating the formation of insoluble ubiquitinated protein (IUP) aggregates, and reduce the early development of diabetic nephropathy. Methods and results Diabetes was induced in mice by intraperitoneally injecting alloxan monohydrate (200 mg/kg/d) twice and administering EGCG3”Me by gavage for 15 d. Reagent case and western blot results showed that, in diabetic kidneys, the carbonyl proteins in the serum increased; and in insoluble protein fraction, 4-hydroxynonenal-modified proteins, IUP aggregates and p62 accumulated; FT-IR study demonstrated that the lipid content, anti-parallel ?-sheet structure and aggregates increased. EGCG3”Me treatment could effectively reverse this process, even better than the negative control treatment. Conclusions EGCG3”Me exhibiting anti-?-sheet-rich IUP aggregate properties, maybe represents a new strategy to impede the progression of diabetic nephropathy and other diabetic complications.

Cai, Shuxian; Zhong, Yuan; Li, Yinhua; Huang, Jianan; Zhang, Jing; Luo, Guoan; Liu, Zhonghua

2013-01-01

118

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

119

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. © 2013 BioFactors 39(5):564-574, 2013. PMID:23553786

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

2013-03-29

120

Insulin-like antigen of mangrove leaves and its anti-diabetic activity in alloxan-induced diabetic rats  

Microsoft Academic Search

The objective of this study was to evaluate the anti-diabetic potential of three mangrove plants, Rhizophora mucronata, Rhizophora apiculata and Rhizophora annamalayana, and to detect the presence of their insulin-like protein. The in vivo anti-diabetic experiment was done on male albino Wister rats. Oral administration of 60?mg?kg leaf powder extract of the three different mangrove plants for 30 days modulated the

Nabeel M. Alikunhi; Kathiresan Kandasamy; Chinthamani Manoharan; Manivannan Subramanian

2011-01-01

121

Insulin-like antigen of mangrove leaves and its anti-diabetic activity in alloxan-induced diabetic rats  

Microsoft Academic Search

The objective of this study was to evaluate the anti-diabetic potential of three mangrove plants, Rhizophora mucronata, Rhizophora apiculata and Rhizophora annamalayana, and to detect the presence of their insulin-like protein. The in vivo anti-diabetic experiment was done on male albino Wister rats. Oral administration of 60?mg?kg leaf powder extract of the three different mangrove plants for 30 days modulated the

Nabeel M. Alikunhi; Kathiresan Kandasamy; Chinthamani Manoharan; Manivannan Subramanian

2012-01-01

122

Hypoglycaemic and anti-diabetic activity of stem bark extracts Erythrina indica in normal and alloxan-induced diabetic rats  

Microsoft Academic Search

The objective of the study is to investigate the alcoholic (AlcE) and aqueous (AqsE) extracts of stem bark of Erythrina indica (Papilionaceae) for hypoglycaemic effects in normal and diabetic rats. Diabetes was induced in rats by a single dose administration of alloxan (120mg\\/kg, i.p.) or by injecting dexamethasone (10mg\\/kg, i.p.) for 10days. In normal rats, AlcE and AqsE had significantly

A. Yashwant Kumar; K. Nandakumar; M. Handral; Sahil Talwar; Daniel Dhayabaran

2011-01-01

123

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

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

2013-01-01

124

Oral hypoglycemic activity of culinary-medicinal mushrooms Pleurotus ostreatus and P. cystidiosus (higher basidiomycetes) in normal and alloxan-induced diabetic Wistar rats.  

PubMed

This study investigates the oral hypoglycemic activity of Pleurotus ostreatus (P.o.) and P. cystidiosus (P.c.) mushrooms on normal and alloxan-induced diabetic Wistar rats. Different doses (250, 500, 750, 1000, and 1250 mg/kg/body weight) of suspensions of freeze-dried and powdered (SFDP) P.o. and P.c. were administered to normal rats, and postprandial serum glucose levels were measured. Optimal time of activity was investigated using the dose 500 mg/kg. Hypoglycemic effect of a single dose of SFDP P.o. and P.c. (500 mg/kg) were investigated using diabetic male and female rats at different stages of estrous cycle and compared with metformin and glibenclamide. Chronic hypoglycemic activity of SFDP P.o. and P.c. (500 mg/kg) was studied using serum glucose levels and glycosylated hemoglobin levels. Maximally effective dose of SFDP P.o. and P.c. was 500 mg/kg. The highest reduction in the serum glucose level was observed 120 minutes after administration of mushrooms. A single dose of P.o. and P.c. significantly (P < 0.05) reduced the serum glucose levels of male diabetic rats. The hypoglycemic activity in female rats was highest in proestrous stage. The hypoglycemic effect of P.o. and P.c. is comparable with metformin and glibenclamide. Daily single administrations of P.o. and P.c. to diabetic rats exert apparent control on the homeostasis of blood glucose. SFDP P.o. and P.c. possessed marked and significant oral hypoglycemic activity. This study suggests the consumption of P.o. and P.c. mushrooms might bring health benefits to mankind as it shows hypoglycemic activity in rats. PMID:23510172

Jayasuriya, W J A B; Suresh, T S; Abeytunga, D; Fernando, G H; Wanigatunga, C A

2012-01-01

125

Comparative evaluation of the anti-diabetic activity of Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by optimized conventional and non conventional extraction methods.  

PubMed

The aim of the present study was to assess the anti-diabetic activity of Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by optimized conventional and non conventional extraction methods. Aqueous and ethanol extracts of Pterocarpus marsupium heartwood were prepared by conventional methods (infusion, decoction, maceration and percolation) and non conventional methods, such as ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE). The crude aqueous extracts were administered orally to both normal and alloxan induced male albino rats (Sprague-Dawley strain). The experimental set up consisted of 48 male albino rats divided into 6 groups: Normal control, diabetic control (sterile normal saline, 1 ml/100 g body weight), standard (gliclazide, 25 mg/1000g of body weight), groups 4-6 (crude aqueous percolation, optimized UAE and MAE extract, 250 mg/1000g of body weight). In acute treatment, the reduction of blood glucose level was statistically significant with the oral administration of UAE and percolation aqueous extracts to the hyperglycemic rats. In sub-acute treatment, the UAE aqueous extract led to consistent and statistically significant (p<0.001) reduction in the blood glucose levels. There was no abnormal change in body weight of the hyperglycemic animals after 10 days of administration of plant extracts and gliclazide. This study justifies the traditional claim and provides a rationale for the use of Pterocarpus marsupium to treat diabetes mellitus. The antidiabetic activity of Pterocarpus marsupium can be enhanced by extracting the heartwood by non conventional method of UAE. PMID:24035955

Devgan, Manish; Nanda, Arun; Ansari, Shahid Husain

2013-09-01

126

The effect of cadmium on visual evoked potentials in alloxane-induced diabetic rats: relation to lipid peroxidation  

Microsoft Academic Search

Fifty-two healthy male Swiss albino rats, aged three months, were used in this study. They were divided into four groups:\\u000a control (c), diabetic (D), cadmium (Cd), and diabetic + Cd (D+Cd). A diabetic condition was induced in D and D + Cd groups\\u000a by administration of alloxane (5 mg\\/100 g). After this treatment, Cd and D + Cd groups were

P. Yargiço?lu; A. A?ar; M. Edremitlio?lu; Y. O?uz; C. Apaydin

1999-01-01

127

Acute effect of Bauhinia forficata on serum glucose levels in normal and alloxan-induced diabetic rats  

Microsoft Academic Search

Experimental diabetes was used to study the acute effect of the n-butanol fraction of Bauhinia forficata Link (Leguminosae) (BF) leaves on the serum glucose levels of rats. Body weight was measured on the day of diabetes induction and on the day of the experiment. Levels of glucose were determined at different doses and times following treatment with BF or with

Fátima Regina Mena Barreto Silva; Bruno Szpoganicz; Moacir Geraldo Pizzolatti; Maria Alice Vieira Willrich; Eliandra de Sousa

2002-01-01

128

The chronic effects of neonatal alloxan-induced diabetes mellitus on ventricular myocyte shortening and cytosolic Ca2+.  

PubMed

Diabetes mellitus is a serious global health problem, and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The chronic effects of neonatal alloxan- (ALX) induced diabetes mellitus on ventricular myocyte contraction and intracellular Ca(2+) transport have been investigated. Ventricular myocyte shortening was measured with a video edge detection system and intracellular Ca(2+) was measured in fura-2 loaded cells by fluorescence photometry. Diabetes was induced in 5-day old male Wistar rats by a single intraperitoneal injection of ALX (200 mg/kg body weight). Experiments were performed 12 months after ALX treatment. Fasting blood glucose was elevated and blood glucose at 60, 120 and 180 min after a glucose challenge (2 g/kg body weight, intraperitoneal) was elevated in diabetic rats compared to age-matched controls. Amplitude of shortening was significantly (P < 0.05) reduced in electrically stimulated myocytes from diabetic hearts (5.70 ± 0.24%) compared to controls (6.48 ± 0.28%). Amplitude of electrically evoked Ca(2+) transients was also significantly (P < 0.05) reduced in myocytes from diabetic hearts (0.11 ± 0.01 fura-2 ratio units) compared to controls (0.15 ± 0.01 fura-2 ratio units). Fractional sarcoplasmic reticulum Ca(2+) release was not significantly (P > 0.05) altered in myocytes from diabetic heart (0.70 ± 0.03 fura-2 ratio units) compared to controls (0.72 ± 0.03 fura-2 ratio units). Amplitude of caffeine-stimulated Ca(2+) transients was significantly (P < 0.05) reduced in myocytes from diabetic hearts (0.43 ± 0.02 fura-2 ratio units) compared to controls (0.51 ± 0.03 fura-2 ratio units). Area under the caffeine-evoked Ca(2+) transient was significantly (P < 0.05) reduced in myocytes from diabetic heart (0.77 ± 0.06 Vsec) compared to controls (1.14 ± 0.12 Vsec). Intracellular Ca(2+) refilling rate during electrical stimulation following application of caffeine was significantly (P < 0.05) slower in myocytes from diabetic heart (0.013 ± 0.001 V/sec) compared to controls (0.031 ± 0.007 V/sec). Depressed shortening may be partly attributed to depressed sarcoplasmic reticulum Ca(2+) transport in myocytes from neonatal ALX-induced diabetic rat heart. PMID:20941530

Howarth, Frank Christopher; Hassan, Zahra; Qureshi, Muhammad Anwar

2010-10-13

129

Antidiabetic Activity of Methanol Leaf Extract of Costus pictus D. DON in Alloxan-induced Diabetic Rats  

Microsoft Academic Search

The methanol extract of Costus pictus (C. pictus )D.DON (Family: Zingiberaceae) leaf was investigated for its anti-diabetic effect in Wistar Albino rats. Diabetes was induced in Albino rats by administration of single doses of alloxan monohydrate (120 mg\\/kg, i.p.). The methanol extract of C. pictus (MECP) at a dose of 120 mg\\/kg, p.o. was administered as single dose per day

Nandhakumar Jothivel; Sethumathi Pudhupalayam Ponnusamy; Malini Appachi; Sengottuvelu Singaravel; Duraisamy Rasilingam; Karthikeyan Deivasigamani; Sivakumar Thangavel

2007-01-01

130

Antidiabetic, antihyperlipidemic and antioxidant activities of methanolic extract of Amaranthus viridis Linn in alloxan induced diabetic rats  

Microsoft Academic Search

The aim of this study was to investigate the antidiabetic, antihyperlipidemic and antioxidant activities of methanolic extract of whole plant of Amaranthus viridis (MEAV) in alloxan (ALX) induced diabetic rats. Diabetes was confirmed after 5 days of single intraperitoneal injection of ALX (140mg\\/kg) in albino Wister rats. MEAV (200 and 400mg\\/kg) and glibenclamide (10mg\\/kg, p.o.) orally administered daily for 15

B. S. Ashok Kumar; K. Lakshman; K. N. Jayaveea; D. Sheshadri Shekar; Saleemulla Khan; B. S. Thippeswamy; Veeresh P. Veerapur

2010-01-01

131

Effect of electromagnetic radiation modulated by biostructures on the course of alloxan-induced diabetes mellitus in rats  

Microsoft Academic Search

Exposure of rats with experimental diabetes mellitus to wide-band electromagnetic radiation generated by He-Ne laser and modulated\\u000a by the pancreas and spleen is informing and phenomenological method prolonging animal life span, normalizing blood glucose\\u000a level, and promoting regeneration of the pancreas.

P. P. Garyaev; A. A. Kokaya; I. V. Mukhina; E. A. Leonova-Garyaeva; N. G. Kokaya

2007-01-01

132

Hypoglycaemic and antidiabetic activity of acetonic extract of Vernonia colorata leaves in normoglycaemic and alloxan-induced diabetic rats  

Microsoft Academic Search

The aqueous extract of Vernonia colorata (Willd.) Drake (Composeae) leaves is used by African traditional medicine practitioners as a remedy for the treatment of diabetes. Our previous studies have shown the hypoglycaemic activity of the aqueous extract of Vernonia colorata leaves (300mg\\/kg, per os) in normoglycaemic rats. The aim of the present study was to investigate the hypoglycaemic and antidiabetic

G. Y. Sy; A. Cissé; R. B. Nongonierma; M. Sarr; N. A. Mbodj; B. Faye

2005-01-01

133

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.

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

2012-01-01

134

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

2012-12-20

135

Antidiabetic, antihyperlipidemic and antioxidant activities of methanolic extract of Amaranthus viridis Linn in alloxan induced diabetic rats.  

PubMed

The aim of this study was to investigate the antidiabetic, antihyperlipidemic and antioxidant activities of methanolic extract of whole plant of Amaranthus viridis (MEAV) in alloxan (ALX) induced diabetic rats. Diabetes was confirmed after 5 days of single intraperitoneal injection of ALX (140 mg/kg) in albino Wister rats. MEAV (200 and 400 mg/kg) and glibenclamide (10 mg/kg, p.o.) orally administered daily for 15 days, blood was withdrawn for glucose determination on 0, 1, 10 and 15 days respectively. On the 15th day, overnight fasted rats were sacrificed and blood was collected for the determination of high density lipoproteins cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), total glycerides (TG) and total proteins (TP). For in vivo antioxidant activity of MEAV, liver tissues were homogenized and the assay of lipid peroxidation and was measured as Malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and total thiols (TT) were performed in control, ALX and MEAV treated rats. MEAV at doses of 200 and 400 mg/kg showed significant reduction is blood glucose, lipid profiles and significant improvement in MDA, GSH, CAT and TT when compared to diabetic control group. In vitro ?-amylase inhibition activity of MEAV was also studied. We concluded that MEAV possess antidiabetic, antihyperlipidemic and antioxidant activities. PMID:20643534

Ashok Kumar, B S; Lakshman, K; Jayaveea, K N; Sheshadri Shekar, D; Saleemulla Khan; Thippeswamy, B S; Veerapur, Veeresh P

2010-07-18

136

Antioxidant Effect of Dietary Supplement Withania somnifera L. Reduce Blood Glucose Levels in Alloxan-Induced Diabetic Rats  

Microsoft Academic Search

The phenolic compounds and flavonoids were determined from the extracts of Withania somnifera root (WSREt) and leaf (WSLEt). The WSREt has 28.26 mg\\/g total phenolic compounds and 17.32 mg\\/g flavonoids, whereas WSLEt\\u000a has 5.4 mg\\/g total phenolic compounds and 5.1 mg\\/g flavonoids. The WSREt, WSLEt and glibenclamide were orally administered\\u000a daily to diabetic rats for 8 weeks. After the treatment, the levels of urine sugar,

Rajangam Udayakumar; Sampath Kasthurirengan; Ayyappan Vasudevan; Thankaraj Salammal Mariashibu; Jesudass Joseph Sahaya Rayan; Chang Won Choi; Andy Ganapathi; Sei Chang Kim

2010-01-01

137

Effect of a Siraitia grosvenori extract containing mogrosides on the cellular immune system of type 1 diabetes mellitus mice.  

PubMed

The purpose of this study was to observe the islet changes of pancreas in insulin-dependent diabetes mellitus (IDDM) mice in comparison to normal mice after application of an extract from Siraitia grosvenori fruits containing mogrosides, in particular, mogroside V. We hypothesized that mogroside extract (MG) attenuates the severity of alloxan-induced IDDM by effects on the immune system. Our data show that IDDM mice exhibited significant injury to pancreatic islets cells, which were atrophic. In addition, alloxan induced a notable increase in the expression of CD8+ lymphocytes to form a dramatic decrease in CD4+/CD8+ ratio (while CD4+ was unchanged). MG, administered to normal and experimental diabetic mice for 4 wk, effectively attenuated the early clinical symptoms, biochemical abnormalities, and pathological damages in pancreatic islets. Furthermore, at low dose, MG regulated the immune imbalance observed in alloxan-induced IDDM mice by up-regulating the CD4+ T-lymphocyte subsets and CD4/CD8 ratio, and altering the intracellular cytokine profiles. The expression of the pro-inflammatory Th1 cytokines: IFN-gamma, TNF-alpha in splenic lymphocytes was altered toward a beneficial Th2 pattern. MG therapy had no effect on normal mice, except that low dosage MG could up-regulate the IL-4 expression levels. The results revealed that MG exhibited antidiabetic effects presumably due to the presence of mogrosides. PMID:16835866

Xiangyang, Qi; Weijun, Chen; Liegang, Liu; Ping, Yao; Bijun, Xie

2006-08-01

138

Effect of soybean seeds alone or in combination with insulin or glibenclamide on serum lipid profiles in alloxan-induced diabetic rats  

Microsoft Academic Search

The present study was conducted to evaluate the effect of soybean seeds administration alone or combined with either insulin or glibenclamide on serum lipid profiles in diabetic rats. Male Wister rats were induced diabetes by a single subcutaneous injection of alloxan 100 mg\\/kg.b.w.The rats randomly divided into six groups (eight rats in each group): The first group served as a

O. H. Aziz

139

The effect of sulfur dioxide inhalation on visual evoked potentials, antioxidant status, and lipid peroxidation in alloxan-induced diabetic rats.  

PubMed

The aim of the study was to investigate the effect of 10 ppm sulfur dioxide (SO(2)) exposure on visual evoked potentials (VEPs), thiobarbituric acid reactive substances (TBARS), and the activities of Cu,Zn superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in diabetes mellitus. Forty healthy male albino rats, aged 3 months, were divided into four equal groups: control (C), sulfur dioxide + control (CSO(2)), diabetic (D), and sulfur dioxide + diabetic (DSO(2)) groups. Experimental diabetes mellitus was induced by IV injection of alloxane monohydrate in a dose of 50 mg/kg body weight. Ten ppm sulfur dioxide was administered to the animals of sulfur dioxide-exposed groups in an exposure chamber for 1 h/day x 7 days/week x 6 weeks while control and diabetic groups were exposed to filtered air in the same condition. SO(2) exposure, though markedly decreasing retina CAT and GSH-Px activities, significantly increased retina Cu,Zn-SOD activity in the diabetic and nondiabetic groups. In contrast to SO(2)-related increase in the activity of Cu,Zn-SOD, decrease in GSH-Px activity was observed in the brain of those groups. Brain CAT activity was unaltered. SO(2) exposure caused the significant elevation in brain TBARS levels of CSO(2) and DSO(2) groups, whereas only in the retina TBARS level of the CSO(2) group. SO(2) exposure caused the significant prolongations of P(1), N(1), P(2), and P(3) components of VEPs in the nondiabetic and all components of VEPs in the diabetic groups. SO(2) exposure also resulted in significant amplitude reductions in both experimental groups. PMID:10871429

A?ar, A; Küçükatay, V; Yargiço?lu, P; Aktekin, B; Kipmen-Korgun, S; Gümü?lü, D; Apaydin, C

2000-08-01

140

Hypoglycemic and antihyperglycemic effects of diethyl ether fraction isolated from the aqueous extract of the leaves of Cogniauxia podoleana Baillon in normal and alloxan-induced diabetic rats  

Microsoft Academic Search

Cogniauxia podoleana Baillon (Cucurbitaceae family) leaves are used in Congolese traditional medicine for the treatment of diabetes mellitus. Based on an increasing number of reports on blood glucose level reduction associated with some saponins and flavonoids isolated from medicinal plants, the hypoglycemic and antihyperglycemic effects of flavonoid and saponin fractions were investigated. Saponin fractions were obtained by the fractionation of

Martin Diatewa; Céline Badila Samba; Théophile Coffi Hondi Assah; Antoine Ange Abena

2004-01-01

141

Regulation of LPS stimulated ROS production in peritoneal macrophages from alloxan-induced diabetic rats: Involvement of high glucose and PPAR?  

Microsoft Academic Search

An increased occurrence of long term bacterial infections is common in diabetic patients. Bacterial cell wall components are described as the main antigenic agents from these microorganisms and high blood glucose levels are suggested to be involved in altered immune response. Hyperglycemia is reported to alter macrophages response to lipopolysaccharide (LPS) and peroxisome proliferators activated receptor gamma (PPAR?) expression. Additionally,

Luiz Fernando de Souza; Fabiano Barreto; Evandro Gomes da Silva; Michael Everton Andrades; Eduardo Linck Machado Guimarães; Guilherme Antonio Behr; José Cláudio Fonseca Moreira; Elena Aida Bernard

2007-01-01

142

In vitro alpha-amylase inhibition and in vivo antioxidant potential of Amaranthus spinosus in alloxan-induced oxidative stress in diabetic rats  

Microsoft Academic Search

Amaranthus spinosus Linn. (Amaranthaceae), commonly known as “Mulluharivesoppu” in Kannada, is used in the Indian traditional system of medicine for the treatment of diabetes. The present study deals with the scientific evaluation of alpha amylase and the antioxidant potential of methanol extract of A. spinosus (MEAS). The aim of this study was to investigate in vitro alpha-amylase enzyme inhibition by

B. S. Ashok Kumar; K. Lakshman; R. Nandeesh; P. A. Arun Kumar; B. Manoj; Vinod Kumar; D. Sheshadri Shekar

2011-01-01

143

The Effect of Sulfur Dioxide Inhalation on Visual Evoked Potentials, Antioxidant Status, and Lipid Peroxidation in Alloxan-Induced Diabetic Rats  

Microsoft Academic Search

The aim of the study was to investigate the effect of 10 ppm sulfur dioxide (SO2) exposure on visual evoked potentials (VEPs), thiobarbituric acid reactive substances (TBARS), and the activities of Cu,Zn\\u000a superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in diabetes mellitus. Forty healthy male albino\\u000a rats, aged 3 months, were divided into four equal groups: control (C),

A. A?ar; V. Küçükatay; P. Yargiço?lu; B. Aktekin; S. Kipmen-Korgun; D. Gümü?lü; C. Apaydin

2000-01-01

144

Effect of methanolic extract of Musa sapientum leaves on gastrointestinal transit time in normal and alloxan induced diabetic rats: possible mechanism of action.  

PubMed

Disorders of gastrointestinal motility have been associated with diabetes mellitus. Hyperglycaemia particularly has been reported to inhibit gastrointestinal transit time while glibenclamide, a sulphonylurea and insulin, both increased transit time. Musa sapientum has also been reported as an antidiabetic agent but there is dearth of information on the effect of this plant on gastrointestinal motility. This study was therefore carried out to investigate the effect of methanolic extract of Musa sapientum leaves (MEMSL) on gastrointestinal transit time (GITT) in male albino rats with and without hyperglycaemia and to elucidate possible mechanism by which this extract functions. Fifty five albino rats were divided into 11 groups of five animals each. All animals were fasted for 24hrs before the begining of the experiment. Group 1 served as control; while the remaining groups (2 - 11) were treated with 250mg/kg; 500mg/kg MEMSL; diabetic control; diabetic treated with 250mg/kg; 500mg/kg MEMSL; diabetic treated with glibenclamide (5mg/kg); normal rats treated with nifedipine (50mg/kg); normal rats treated with calcium chloride (CaCl2) only (10mg/kg); groups 10 and 11 were both pretreated with CaCl2 and subsequently treated with 250mg/kg and 500mg/kg MEMSL respectively. All plant extracts used for treatments were dissolved in normal saline and administered orally using orogastric tube. Charcoal meal was used as marker in the estimation of GITT. The study showed significant decrease in GITT in the normal rats treated with 250mg/kg and 500mg/kg of extract. However, in the diabetic rats treated with 500mg/kg MEMSL, there was significant increase in GITT and this is comparable with the gut response to glibenclamide (5mg/kg). Musa sapientum extract produced significant decrease in transit time in the calcium chloride pre-treated normal rats and this is comparable to the effect observed in Nifedipine treated group. The significant reduction in GITT produced by MEMSL in the normal rats reflects a strong possibility of MEMSL acting as calcium channel antagonist through the voltage gated calcium channel which may be due to the presence of alkaloids, saponins, cardenolides. There is the possibility of the extract acting as an inhibitor of potassium channel at higher concentration as observed in glibenclamide treated groups. PMID:22314993

Adewoye, E O; Ige, A O; Latona, C T

2011-11-23

145

Pretreatment effect of magnesium on alloxan induced hyperglycemia in rats.  

PubMed

The role of vitamins and mineral supplementation in the management of Diabetes mellitus is not well elucidated. We therefore carried out a preliminary study to assess the effect of prior administration of Magnesium on induction of alloxan diabetes, a model of type 1 diabetes mellitus. Twenty Male albino rats were used for this study. The animals were divided into 4 groups of 5 animals each. Animals in group 1 were normal rats and were not given any treatment, these served as healthy control. Animals in group 2 were diabetic rats that were not given any treatment, they served as diabetic control. Animals in group 3 were treated with magnesium (100mg/kg) intraperitoneally one hour prior to alloxan (150mg/kg) administration. Animals in group 4 were given intraperitoneal injection of magnesium (100mg/kg) once, and blood samples were obtained one hour after administration. Blood samples were obtained from all animals after 48 hours and plasma glucose levels determined using the glucose oxidase method. There was significant increase (p<0.001) in plasma glucose level in the alloxan treated group when compared with the control. There was also a significant increase (p<0.01) in magnesium-pretreated diabetic group. However, there was a significant reduction (p<0.01) in blood glucose level 48 hours after alloxan administration in the magnesium pre-treated diabetic group when compared with the diabetic controls. Magnesium pretreatment may delay the onset of alloxan induced hyperglycemia and this may be due to the scavenging effect of magnesium on the highly reactive hydroxyl radicals (OH) which was generated through alloxan reaction. PMID:22416651

Ige, O A; Adewoye, E O; Olaleye, S B; Salami, A T

2010-12-01

146

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

2011-08-04

147

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  

Microsoft Academic Search

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

Semantee Bhattacharya; Prasenjit Manna; Ratan Gachhui; Parames C. Sil

148

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

PubMed

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 ?-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 ?-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. PMID:21982801

Bhattacharya, Semantee; Manna, Prasenjit; Gachhui, Ratan; Sil, Parames C

2011-09-22

149

In vitro antioxidant and in vivo antidiabetic potential of the methanol extract of Ficus glumosa Del (Moraceae) stem bark in alloxan-induced diabetic mice  

Microsoft Academic Search

Ficus glumosa Del (Moraceae) commonly called “African rock fig” is a large tree indigenous to southern part of Nigeria. Its stem bark has\\u000a been of interest to researchers because of its use in the treatment of various disease conditions in Nigerian traditional\\u000a medicine. The present study was aimed at evaluating the antidiabetic and antioxidant properties of the methanol extract of

Ifeanyi Innocent Madubunyi; Samuel Okwudili Onoja; Isaac Uzoma Asuzu

150

Antidiabetic and antioxidant effects of the methanol extract of Bridelia micrantha (Hochst) Baill. (Euphorbiaceae) leaves on alloxan-induced diabetic albino mice  

Microsoft Academic Search

Bridelia micrantha (Hochst) Baill. (Euphorbiaceae), commonly known in English as “coast gold leaf” or “ogaofia” (the boss of the bush) in Igbo,\\u000a is a semi-deciduous to deciduous tree up to 20 m tall with a dense rounded crown and tall, and bare stem indigenous to southern\\u000a part of Nigeria. Its stem bark, which is yellow grey and smooth to slightly rough,

O. A. Adika; Ifeanyi Innocent Madubunyi; I. U. Asuzu

151

Anti-diabetic activity of alcoholic extract of Celosia argentea Linn. seeds in rats.  

PubMed

Celosia argentea Linn. commonly known as "Cocks Comb" and its seeds are widely used in Indian folk medicine for the treatment of diabetes mellitus. This study was undertaken to evaluate the effect of an alcoholic extract of Celosia argentea seeds (ACAS) on blood glucose and body weight in alloxan-induced diabetic rats. ACAS was found to reduce the increase of blood glucose in alloxan-induced diabetic rats (27.8% at 250 mg/kg and 38.8% at 500 mg/kg body weight). Chronic administration of ACAS significantly (p<0.01) reduced the blood glucose in alloxan-induced diabetic rats for two weeks. Also the extract prevented a decrease in body weight in alloxan-induced diabetic rats. These results suggest that the ACAS possesses anti-diabetic activity in alloxan-induced diabetic rats. PMID:11995938

Vetrichelvan, Thangarasu; Jegadeesan, Maniappan; Devi, Bangaru Adigalar Uma

2002-04-01

152

Study on anti-diabetic activities of crude methanolic extracts of Loranthus micranthus (Linn.) sourced from five different host trees.  

PubMed

The hypoglycaemic and anti-hyperglycemic activities of dried leaves of Loranthus micranthus (Linn.) (Loranthaceae), parasitic on Persea americana, Baphia nitda, Kola acuminata, Pentaclethra macrophylla, Azadirchta indica, were evaluated in normoglycemic and alloxan-induced diabetic albino rats. Normoglycemic and alloxan-induced diabetic rats were treated (intraperitoneally) with 200 mg/kg of the respective methanolic extracts of Loranthus micranthus (Linn.), glibenclamide (positive control), and 20% (v/v) Tween 20 solution (negative control). The sugar levels of the withdrawn blood samples were determined by o-toluidine spectrophotometric method. The studies indicate that the crude methanolic extract of Loranthus micranthus (Linn.) exhibited statistically significant hypoglycaemic (P < 0.001) and anti-hyperglycemic (P < 0.001) activities in normoglycemic and alloxan-induced diabetic albino rats, respectively. The hypoglycaemic effect was found to be dose-dependent. The maximum effect of the mistletoe extract (400 mg/kg) from Persea americana on alloxan-induced diabetic rats was found to be statistically comparable with that of the positive control, glibenclamide, at 24 h after administration, with a percentage reduction of blood sugar levels of 82.59 and 83.34%, respectively. Acute toxicity tests of the methanolic extracts of Persea americana, Baphia nitda, Kola acuminata, Pentaclethra macrophylla, Azadirchta indica host trees in mice gave LD(50) values of 11650, 11650, 5900, 5900 and 5900 mg/kg, respectively, which are all within the practically non-toxic range. The methanolic extract of African mistletoe was found to be a good candidate for alternative and/or complimentary medicine in the management of diabetes mellitus. The leaves of the Eastern Nigerian species of the African mistletoe harvested from Kola acuminata, Azadirchta indica and Baphia nitda host trees exhibited comparatively better anti-hyperglycemic activities among the host trees studied. PMID:15507325

Osadebe, P O; Okide, G B; Akabogu, I C

2004-12-01

153

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

154

Antioxidant and Hypolipidemic Effect of Plumeria Rubra L. in Alloxan Induced Hyperglycemic Rats  

Microsoft Academic Search

Antioxidant and hypolipidemic activity of the flovone glycoside isolated from Plumeria rubra L. was carried in alloxan induced hyperglycemic rats. The flavonoid treatment produced a significant reduction in the level of serum triglycerides, while there was no reduction in the serum cholesterol and glucose. Antioxidant activity of the drug was also confirmed through in vitro studies.

A. JOHN MERINA; D. SIVANESAN; V. HAZEENA BEGUM; N. SULOCHANA

155

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

156

In vitro and in vivo protective effect of Ganoderma lucidum polysaccharides on alloxan-induced pancreatic islets damage  

Microsoft Academic Search

This study was undertaken to investigate the protective effect against alloxan-induced pancreatic islets damage by Ganoderma lucidum Polysaccharides (Gl-PS) isolated from the fruiting body of Ganoderma lucidum (Leyss. ex Fr.) Karst. In vitro, alloxan caused dose-dependent toxicity on the isolated pancreatic islets. Pre-treatment of islets with Gl-PS for 12 h and 24 h significantly reversed alloxan-induced islets viability loss. Gl-PS

Hui-Na Zhang; Jing-Hua He; Lan Yuan; Zhi-Bin Lin

2003-01-01

157

Alterations in immunological reactivity in encephalomyocarditis virus-induced murine diabetes. I. Defective primary IgM plaque forming cell responses to sheep erythrocytes: correction by islet cell transplantation.  

PubMed Central

Increasing data suggest a possible viral aetiology of juvenile onset, insulin-dependent diabetes mellitus. The M variant of the encephalomyocarditis (EMC) virus infects murine pancreatic beta cells and causes a diabetes like syndrome in susceptible strains of mice. Abnormalities in immunological function have been documented in patients with diabetes mellitus and in spontaneous, streptozotocin-induced and alloxan-induced diabetes in animals. The present study documents a significant impairment of the ability of mice with EMC virus (M variant)-induced diabetes to generate a direct, IgM PFC response after in vivo immunization with sheep erythrocytes. This abnormality appears to be a direct consequence of the diabetic state and not EMC virus infection, per se, since mice infected with EMC virus that do not become diabetic have normal direct PFC responses and islet cell transplantation, which cures the diabetes, corrects the defect in PFC responsiveness.

Handwerger, B S; Fernandes, G; Riehm, T; Yoon, J W; Sutherland, D E; Brown, D M

1985-01-01

158

Diabetes induces apoptosis in lymphocytes  

Microsoft Academic Search

The occurrence of DNA fragmentation in lymphocytes obtained from alloxan-induced diabetic rats and diabetic patients was investigated. A high proportion of apoptotic lymphocytes in diabetic states may explain the impaired immune function in poorly controlled diabetic patients. Rat mesenteric lymph node lymphocytes were analysed for DNA fragmentation by using flow cytometry and agarose gel, and for chromatin condensation by Hoescht

R Otton; F G Soriano; R Verlengia; R Curi

2004-01-01

159

The genetics of diabetes susceptibility in mice  

Microsoft Academic Search

The factors associated with a diabetes-susceptible genotype in mice exhibiting various forms of heritable glucose intolerance syndromes are discussed. Genetic models of insulin-dependent and non-insulin-dependent diabetes in mice are described. Although single gene mutations can be defined for each model that are major contributors to diabetogenic stress, polygenic interactions are required for the expression of a diabetic phenotype, and environmental

EDWARD H. LEITER

1989-01-01

160

Study on anti-diabetic activities of crude methanolic extracts of Loranthus micranthus (Linn.) sourced from five different host trees  

Microsoft Academic Search

The hypoglycaemic and anti-hyperglycemic activities of dried leaves of Loranthus micranthus (Linn.) (Loranthaceae), parasitic on Persea americana, Baphia nitda, Kola acuminata, Pentaclethra macrophylla, Azadirchta indica, were evaluated in normoglycemic and alloxan-induced diabetic albino rats. Normoglycemic and alloxan-induced diabetic rats were treated (intraperitoneally) with 200mg\\/kg of the respective methanolic extracts of Loranthus micranthus (Linn.), glibenclamide (positive control), and 20% (v\\/v) Tween

P. O. Osadebe; G. B. Okide; I. C. Akabogu

2004-01-01

161

Exendin-4 Modulates Diabetes Onset in Nonobese Diabetic Mice  

PubMed Central

Activation of the glucagon-like peptide-1 receptor (GLP-1R) is associated with expansion of ?-cell mass due to stimulation of cell proliferation and induction of antiapoptotic pathways coupled to ?-cell survival. Although the GLP-1R agonist Exenatide (exendin-4) is currently being evaluated in subjects with type 1 diabetes, there is little information available about the efficacy of GLP-1R activation for prevention of experimental type 1 diabetes. We examined the consequences of exendin-4 (Ex-4) administration (100 ng once daily and 2 ?g twice daily) on diabetes onset in nonobese diabetic mice beginning at either 4 or 9 wk of age prior to the onset of diabetes. Ex-4 treatment for 26 wk (2 ?g twice daily) initiated at 4 wk of age delayed the onset of diabetes (P = 0.007). Ex-4-treated mice also exhibited a significant reduction in insulitis scores, enhanced ?-cell mass, and improved glucose tolerance. Although GLP-1R mRNA transcripts were detected in spleen, thymus, and lymph nodes from nonobese diabetic mice, Ex-4 treatment was not associated with significant changes in the numbers of CD4+ or CD8+ T cells or B cells in the spleen. However, Ex-4 treatment resulted in an increase in the number of CD4+ and CD8+ T cells in the lymph nodes and a reduction in the numbers of CD4+CD25+Foxp3+ regulatory T cells in the thymus but not in lymph nodes. These findings demonstrate that sustained GLP-1R activation in the absence of concomitant immune intervention may be associated with modest but significant delay in diabetes onset in a murine model of type 1 diabetes.

Hadjiyanni, Irene; Baggio, Laurie L.; Poussier, Philippe; Drucker, Daniel J.

2008-01-01

162

Dissecting autoimmune diabetes through genetic manipulation of non-obese diabetic mice  

Microsoft Academic Search

Type 1 diabetes results from a genetically and immunologically complex autoimmune process that is specifically directed against the pancreatic beta cells. Non-obese diabetic mice spontaneously develop a form of autoimmune diabetes closely resembling the disease in humans. This happens because, like human diabetic patients, non-obese diabetic mice have an unfortunate combination of apparently normal alleles at numerous loci associated with

Y. Yang; P. Santamaria

2003-01-01

163

Development of diabetic nephropathy in nude mice.  

PubMed

Background-Immune dysfunction is very common in diabetes mellitus (DM). However, there is no evidence whether such immune dysfunction can influence the development of DM, especially, the development of diabetic nephropathy (DN). Aim-To investigate the influence of absence of T cells on DN. Materials and Methods-Balb/c nude mice and Balb/c wide type nude (WT) mice were injected with streptozotocin (STZ). Serum TNF-?, blood glucose, body weight, urine albumin/creatinine ratio and rate of kidney weight to body weight (KW/BW) were measured. Results-After modeling, there was no difference of blood glucose level between nude mice and WT mice except at week 2 (28.3±4.9 mmol/L vs. 23.1±3.9 mmol/L, P<0.01). At week 4, the serum TNF-? level of nude mice got to 175.08±46.03 pg/mL (P<0.05, compared with baseline level 80.19±8.46 pg/mL), whereas the TNF-? levels of WT mice kept stable. At week 4, the body weight of nude mice was lower than that of WT mice (14.7±3.15 g vs. 17.97±2.85 g, p<0.05); the urine Alb/Cr of nude mice was higher than that of WT mice (50.96±5.57 mg/mmol vs. 41.09±5.79 mg/mmol, P<0.05); the KW/BW of nude mice was higher than that of WT mice (0.01352±0.00163 vs. 0.01173±0.00131, P<0.05). Correlation analysis showed urine Alb/Cr positively correlated with serum TNF-? level at week 4 (r=0.588, P<0.01). At week 4, the increase of type IV collagen in the glomeruli was more prominent in diabetic nude mice than in diabetic WT mice (P<0.05). Conclusions-Absence of T cells in DM might influence the development of DN. PMID:23666500

Lin, Shan; Xu, Peng-Cheng; Huang, Qian-E; Jia, Jun-Ya; Jia, Zhong-Hui; Wei, Li; Zheng, Zhen-Feng; Shang, When-Ya

2013-05-10

164

Evaluation of the Hypoglycemic Activity of Cucumis metuliferus (Cucurbitaceae) Fruit Pulp Extract in Normoglycemic and Alloxan-Induced Hyperglycemic Rats  

PubMed Central

The hypoglycemic effects of the fruit extract of C. metuliferus was investigated in normoglycemic and alloxan-induced hyperglycemic rats. The results showed that there was an insignificant (P > 0.05) decrease in the blood glucose concentration of normoglycemic rats treated with oral doses of 1000 and 1500 mg/kg of the extract. On the other hand, 500 mg/kg of the fruit extract produced an insignificant (P > 0.05) decrease in blood glucose levels of alloxan-treated rats, while 1000 and 1500 mg/kg oral dose points produced a significant (P < 0.05) decrease in the blood glucose concentration of hyperglycemic rats comparable to that produced by tolbutamide. From this study, the data suggested that the fruit extract did not alter the BGC level in normoglycemic rats, but had a potential hypoglycemic property in alloxan-induced hyperglycemic rats.

Jimam, NS; Wannang, NN; Omale, S; Gotom, B

2010-01-01

165

Spontaneous Autoimmune Diabetes in Monoclonal T Cell Nonobese Diabetic Mice  

PubMed Central

It has been established that insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice results from a CD4+ and CD8+ T cell–dependent autoimmune process directed against the pancreatic beta cells. The precise roles that beta cell–reactive CD8+ and CD4+ T cells play in the disease process, however, remain ill defined. Here we have investigated whether naive beta cell–specific CD8+ and CD4+ T cells can spontaneously accumulate in pancreatic islets, differentiate into effector cells, and destroy beta cells in the absence of other T cell specificities. This was done by introducing Kd– or I-Ag7–restricted beta cell–specific T cell receptor (TCR) transgenes that are highly diabetogenic in NOD mice (8.3- and 4.1-TCR, respectively), into recombination-activating gene (RAG)-2–deficient NOD mice, which cannot rearrange endogenous TCR genes and thus bear monoclonal TCR repertoires. We show that while RAG-2?/? 4.1-NOD mice, which only bear beta cell–specific CD4+ T cells, develop diabetes as early and as frequently as RAG-2+ 4.1-NOD mice, RAG-2?/? 8.3-NOD mice, which only bear beta cell–specific CD8+ T cells, develop diabetes less frequently and significantly later than RAG-2+ 8.3-NOD mice. The monoclonal CD8+ T cells of RAG-2?/? 8.3-NOD mice mature properly, proliferate vigorously in response to antigenic stimulation in vitro, and can differentiate into beta cell–cytotoxic T cells in vivo, but do not efficiently accumulate in islets in the absence of a CD4+ T cell–derived signal, which can be provided by splenic CD4+ T cells from nontransgenic NOD mice. These results demonstrate that naive beta cell– specific CD8+ and CD4+ T cells can trigger diabetes in the absence of other T or B cell specificities, but suggest that efficient recruitment of naive diabetogenic beta cell–reactive CD8+ T cells to islets requires the assistance of beta cell–reactive CD4+ T cells.

Verdaguer, Joan; Schmidt, Dennis; Amrani, Abdelaziz; Anderson, Brad; Averill, Nuzhat; Santamaria, Pere

1997-01-01

166

Cannabidiol arrests onset of autoimmune diabetes in NOD mice  

Microsoft Academic Search

We have previously reported that cannabidiol (CBD) lowers the incidence of diabetes in young non-obese diabetes-prone (NOD) female mice. In the present study we show that administration of CBD to 11e14 week old female NOD mice, which are either in a latent diabetes stage or with initial symptoms of diabetes, ameliorates the manifestations of the disease. Diabetes was diagnosed in

Lola Weiss; Michael Zeira; Shoshana Reich; Shimon Slavin; Itamar Raz; Raphael Mechoulam; Ruth Gallily

2007-01-01

167

Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice  

Microsoft Academic Search

Aims\\/hypothesis  1,25-dihydroxyvitamin D3, the active form of vitamin D, prevents Type 1 diabetes in non-obese diabetic (NOD) mice. Epidemiological data show a threefold increase in human Type 1 diabetes when vitamin D deficiency was present in the first months of life. To evaluate whether a similar dietary deficiency affects diabetes incidence in NOD mice, we generated NOD mice with vitamin D

A. Giulietti; C. Gysemans; K. Stoffels; E. van Etten; B. Decallonne; L. Overbergh; R. Bouillon; C. Mathieu

2004-01-01

168

Proteasome activity in experimental diabetes  

Microsoft Academic Search

Numerous studies have indicated that oxidative stress contributes to the development and progression of diabetes and other\\u000a related complications. Since the ubiquitin-proteasome pathway is involved in degradation of oxidized proteins, it is to be\\u000a expected that alterations in proteasome-dependent proteolysis accompany diabetes. This paper focuses on the role of the proteasome\\u000a in alloxan-induced experimental diabetes. The changes in proteasomal activity

Albena Alexandrova; Lubomir Petrov; Margarita Kirkova

2006-01-01

169

Blood-stage malaria infection in diabetic mice.  

PubMed Central

Infection of mice with blood-stage Plasmodium yoelii and P. chabaudi malaria induced hypoglycaemia in normal mice and normalized the hyperglycaemia of mice made moderately diabetic with streptozotocin (STZ). Injection of parasite supernatants induced hypoglycaemia accompanied by hyperinsulinaemia in normal mice, and in STZ-diabetic mice induced a profound drop in blood glucose and restored insulin secretion; however, severely diabetic mice (two injections of STZ) remained hyperglycaemic with no change in insulin levels. We conclude that malaria infection and parasite-derived molecules lower blood glucose concentration, but only in the presence of some residual pancreatic function. Diabetic mice were less anaemic, exerted a significant control of parasitaemia, and showed enhanced phagocytic activity compared with normal mice.

Elased, K; De Souza, J B; Playfair, J H

1995-01-01

170

Blood-stage malaria infection in diabetic mice.  

PubMed

Infection of mice with blood-stage Plasmodium yoelii and P. chabaudi malaria induced hypoglycaemia in normal mice and normalized the hyperglycaemia of mice made moderately diabetic with streptozotocin (STZ). Injection of parasite supernatants induced hypoglycaemia accompanied by hyperinsulinaemia in normal mice, and in STZ-diabetic mice induced a profound drop in blood glucose and restored insulin secretion; however, severely diabetic mice (two injections of STZ) remained hyperglycaemic with no change in insulin levels. We conclude that malaria infection and parasite-derived molecules lower blood glucose concentration, but only in the presence of some residual pancreatic function. Diabetic mice were less anaemic, exerted a significant control of parasitaemia, and showed enhanced phagocytic activity compared with normal mice. PMID:7882567

Elased, K; De Souza, J B; Playfair, J H

1995-03-01

171

Disruption of IRS-2 causes type 2 diabetes in mice  

Microsoft Academic Search

Human type 2 diabetes is characterized by defects in both insulin action and insulin secretion. It has been difficult to identify a single molecular abnormality underlying these features. Insulin-receptor substrates (IRS proteins) may be involved in type 2 diabetes: they mediate pleiotropic signals initiated by receptors for insulin and other cytokines. Disruption of IRS-1 in mice retards growth, but diabetes

Dominic J. Withers; Julio Sanchez Gutierrez; Heather Towery; Deborah J. Burks; Jian-Ming Ren; Stephen Previs; Yitao Zhang; Dolores Bernal; Sebastian Pons; Gerald I. Shulman; Susan Bonner-Weir; Morris F. White

1998-01-01

172

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  

Microsoft Academic Search

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

R. Kh. Khafiz'yanova; M. M. Minnebaev; R. M. Gallyamov; R. S. Latypov; A. R. Gosmanov; G. N. Aleeva

2003-01-01

173

PPAR? activation protects endothelial function in diabetic mice.  

PubMed

Recent evidence highlights the therapeutic potential of peroxisome proliferator-activated receptor-? (PPAR?) agonists to increase insulin sensitivity in diabetes. However, the role of PPAR? in regulating vascular function is incompletely characterized. We investigate whether PPAR? activation improves endothelial function in diabetic and obese mice. PPAR? knockout (KO) and wild-type (WT) mice fed with high-fat diet and db/db mice were used as diabetic mouse models, compared with PPAR? KO and WT mice on normal diet and db/m(+) mice. Endothelium-dependent relaxation (EDR) was measured by wire myograph. Flow-mediated vasodilatation (FMD) was measured by pressure myograph. Nitric oxide (NO) production was examined in primary endothelial cells from mouse aortae. PPAR? agonist GW1516 restored EDRs in mouse aortae under high-glucose conditions or in db/db mouse aortae ex vivo. After oral treatment with GW1516, EDRs in aortae and FMDs in mesenteric resistance arteries were improved in obese mice in a PPAR?-specific manner. The effects of GW1516 on endothelial function were mediated through phosphatidylinositol 3-kinase (PI3K) and Akt with a subsequent increase of endothelial nitric oxide synthase (eNOS) activity and NO production. The current study demonstrates an endothelial-protective effect of PPAR? agonists in diabetic mice through PI3K/Akt/eNOS signaling, suggesting the therapeutic potential of PPAR? agonists for diabetic vasculopathy. PMID:22933110

Tian, Xiao Yu; Wong, Wing Tak; Wang, Nanping; Lu, Ye; Cheang, Wai San; Liu, Jian; Liu, Limei; Liu, Yahan; Lee, Susanna Sau-Tuen; Chen, Zhen Yu; Cooke, John P; Yao, Xiaoqiang; Huang, Yu

2012-08-28

174

Diabetes causes marked changes in lymphocyte metabolism  

Microsoft Academic Search

An enhanced susceptibility to infections is well known to occur in a poorly controlled diabetic state. Since glucose and glutamine are essential for lymphocyte function, we investigated whether their metabolism is changed in lymphocytes obtained from mesenteric lymph nodes of alloxan-induced diabetic rats (40 mg\\/kg body weight). The activities of hexokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase (G6PDH), citrate synthase and phosphate-dependent glutaminase

R Otton; J R Mendonça; R Curi

2002-01-01

175

Lipid peroxidation and antioxidant enzymes in erythrocytes and tissues in aged diabetic rats.  

PubMed

Antidiabetic treatment with powdered fruit of Capparis decidua decreased alloxan induced lipid peroxidation (LPO) significantly in erythrocytes, kidney and heart. Erythrocyte superoxide dismutase (SOD) activity decreased while the kidney and heart SOD increased in diabetic animals. These alterations in SOD were counteracted by insulin as well as with powdered fruit of C. decidua. Increased catalase (CAT) activity in erythrocytes, liver, kidney and heart with C. decidua treatment indicate that the treatment may neutralize H2O2 toxicity by its increased decomposition by CAT. Result shows that treatment with C. decidua lowers alloxan induced LPO and alters SOD and CAT enzymes to reduce oxidative stress. PMID:9315241

Yadav, P; Sarkar, S; Bhatnagar, D

1997-04-01

176

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

177

Podocyte-specific overexpression of human angiotensin-converting enzyme 2 attenuates diabetic nephropathy in mice  

PubMed Central

Angiotensin-converting enzyme 2 (ACE2) degrades angiotensin II to angiotensin-(1–7) and is expressed in podocytes. Here we overexpressed ACE2 in podocytes in experimental diabetic nephropathy using transgenic methods where a nephrin promoter drove the expression of human ACE2. Glomeruli from these mice had significantly increased mRNA, protein, and activity of ACE2 compared to wild-type mice. Male mice were treated with streptozotocin to induce diabetes. After 16 weeks, there was no significant difference in plasma glucose levels between wild-type and transgenic diabetic mice. Urinary albumin was significantly increased in wild-type diabetic mice at 4 weeks, whereas albuminuria in transgenic diabetic mice did not differ from wild-type nondiabetic mice. However, this effect was transient and by 16 weeks both transgenic and nontransgenic diabetic mice had similar rates of proteinuria. Compared to wild-type diabetic mice, transgenic diabetic mice had an attenuated increase in mesangial area, decreased glomerular area, and a blunted decrease in nephrin expression. Podocyte numbers decreased in wild-type diabetic mice at 16 weeks, but were unaffected in transgenic diabetic mice. At 8 weeks, kidney cortical expression of transforming growth factor-?1 was significantly inhibited in transgenic diabetic mice as compared to wild-type diabetic mice. Thus, the podocyte-specific overexpression of human ACE2 transiently attenuates the development of diabetic nephropathy.

Nadarajah, Renisha; Milagres, Rosangela; Dilauro, Marc; Gutsol, Alex; Xiao, Fengxia; Zimpelmann, Joseph; Kennedy, Chris; Wysocki, Jan; Batlle, Daniel; Burns, Kevin D

2012-01-01

178

Podocyte-specific overexpression of human angiotensin-converting enzyme 2 attenuates diabetic nephropathy in mice.  

PubMed

Angiotensin-converting enzyme 2 (ACE2) degrades angiotensin II to angiotensin-(1-7) and is expressed in podocytes. Here we overexpressed ACE2 in podocytes in experimental diabetic nephropathy using transgenic methods where a nephrin promoter drove the expression of human ACE2. Glomeruli from these mice had significantly increased mRNA, protein, and activity of ACE2 compared to wild-type mice. Male mice were treated with streptozotocin to induce diabetes. After 16 weeks, there was no significant difference in plasma glucose levels between wild-type and transgenic diabetic mice. Urinary albumin was significantly increased in wild-type diabetic mice at 4 weeks, whereas albuminuria in transgenic diabetic mice did not differ from wild-type nondiabetic mice. However, this effect was transient and by 16 weeks both transgenic and nontransgenic diabetic mice had similar rates of proteinuria. Compared to wild-type diabetic mice, transgenic diabetic mice had an attenuated increase in mesangial area, decreased glomerular area, and a blunted decrease in nephrin expression. Podocyte numbers decreased in wild-type diabetic mice at 16 weeks, but were unaffected in transgenic diabetic mice. At 8 weeks, kidney cortical expression of transforming growth factor-?1 was significantly inhibited in transgenic diabetic mice as compared to wild-type diabetic mice. Thus, the podocyte-specific overexpression of human ACE2 transiently attenuates the development of diabetic nephropathy. PMID:22475818

Nadarajah, Renisha; Milagres, Rosangela; Dilauro, Marc; Gutsol, Alex; Xiao, Fengxia; Zimpelmann, Joseph; Kennedy, Chris; Wysocki, Jan; Batlle, Daniel; Burns, Kevin D

2012-04-04

179

Structural and functional studies on the transformation of the intestinal mucosa in rats with experimental diabetes  

Microsoft Academic Search

Summary Twenty days after the onset of alloxan-induced diabetes, a villous hyperplasia has developed in the intestines of rats having free access to food. The transformation is characterised by a considerable increase in the area of the villous surface, caused by an enhanced mitotic activity in the crypts. The absorption of glucose or methionine by jejunal loops, whether expressed in

H. Lorenz-Meyer; F. Thiel; H. Menge; H. Gottesbüren; E. O. Riecken

1977-01-01

180

Artificial Pancreas Using Living Beta Cells: Effects on Glucose Homeostasis in Diabetic Rats  

Microsoft Academic Search

An artificial pancreas consisting of beta cells cultured on synthetic semipermeable hollow fibers was tested in rats with alloxan-induced diabetes. When implanted ex vivo as arteriovenous shunts in the circulatory system these devices lowered concentrations of plasma glucose from 533 to between 110 and 130 milligrams per 100 milliliters, increased concentrations of plasma insulin, and restored intravenous glucose tolerance tests

William L. Chick; John J. Perna; Vilma Lauris; David Low; Pierre M. Galletti; Georg Panol; Anthony D. Whittemore; Arthur A. Like; Clark K. Colton; Michael J. Lysaght

1977-01-01

181

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

182

Blood glucose, glutathione, and total keto-acids levels in alloxan-diabetic rats.  

PubMed

This study deals with investigations in diabetic disorders. Experiments were carried out on alloxan-induced diabetes in albino rats. Blood glucose, keto acids, and glutathione were determined before and after induction of alloxan diabetes. Blood glucose and keto acids showed an increase after administration of alloxan. Glutathione showed a drop after 1/2 hour, then began to increase till it reached its normal level after 48 hours from the beginning of the diabetic state. The results are discussed. PMID:605626

El-Hawary, Z; El-Hawary, M F; Morcus, S R

1977-12-01

183

Can garlic oil ameliorate diabetes-induced oxidative stress in a rat liver model? A correlated histological and biochemical study.  

PubMed

This study aimed to characterise the structural changes in liver of an alloxan-induced diabetic rat and to explain such changes in terms of the biochemical changes in free radicals and antioxidants. In addition, it aimed to determine the potential ability of garlic oil to alter these changes. The study groups were: control (n=12), alloxan-induced diabetic rats (n=10) and alloxan-induced diabetic rats treated with garlic oil (10 mg/kg body weight (n=10)). Markers of oxidative stress were assessed. Small pieces of the liver were processed for transmission electron microscopic study. Garlic oil caused a significant decrease in levels of LPO in plasma (0.26 vs 0.53), erythrocyte lysate (14.4 vs 24.8) and liver tissue homogenate (1.04 vs 2.08), whereas those of thiols were significantly elevated (1.2 vs 0.46), (24 vs 15) in plasma and erythrocyte lysate respectively. SOD activity and G-S-T activity were significantly elevated in erythrocyte lysate (5.7 vs 3.3) (377 vs 179) and liver homogenate (1.4 vs 0.5) (752 vs 623) respectively after garlic oil administration. Ultrastructural study of the liver confirmed the ability of garlic to retard lipid peroxidation of cellular membranes induced by oxidative stress associated with diabetes. Therefore, garlic could normalise oxidative stress in alloxan-induced diabetic rats. PMID:23856496

Abdultawab, Hanem Saad; Ayuob, Nasra N

2013-07-12

184

Some toxicological studies of Momordica charantia L. on albino rats in normal and alloxan diabetic rats.  

PubMed

Momordica charantia L. (MC) (Cucurbitaceae) commonly known as balsam pear, bitter gourd or karela, used in several purposes in traditional medicine is an important medicinal plant. Two sets of experiments were carried out, the first experiment indicated that the LD(50) for MC juice and alcoholic extracts were 91.9 and 362.34 mg/100g b.wt., respectively, of subcutaneously "s.c." injected mice. The toxic signs were recorded within the first 24 h post-injection. The second experiment was performed to evaluate the effect of MC juice and alcoholic extracts on blood glucose and other biochemical parameters in normal and diabetic rats. Both extracts induced a significant decrease in serum glucose levels in normal and diabetic rats. The two extracts did not show any significant effect in urea, creatinine, ALT, AST and AP in normal rat, while in diabetic rats the two extracts caused a significant decrease in serum urea, creatinine, ALT, AST, AP, cholesterol and triglyceride levels. Also, these results suggested that MC extracts possesses anti-diabetic, hepato-renal protective and hypolipidemic effect in alloxan-induced diabetic rats. Thus, MC is alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus. PMID:16815658

Abd El Sattar El Batran, Seham; El-Gengaihi, Souad E; El Shabrawy, Osama A

2006-05-26

185

Gymnema montanum H. protects against alloxan-induced oxidative stress and apoptosis in pancreatic beta-cells.  

PubMed

The present study evaluated the molecular mechanism of antidiabetic property of G. montanum leaf extract (GLEt) against alloxan-induced apoptotic cell death in rat insulinoma cells (RINm5F). The pre-treatment of GLEt (5 microg and 10 microg/ml) resulted in significant decrease in intracellular Ca(2+) concentration, nitric oxide (NO) production along with increase in mitochondrial membrane potential in alloxan (7mM/ml) treated cells. Further GLEt reduced apoptosis by inhibiting the release of cytochrome c and subsequent cleavage of PARP and caspase-3. The immunochemical staining of 8-hydroxydeoxyguanosine (8-OHdG) also evidenced the suppression of oxidative stress by GLEt. The cell cycle analysis, annexin-V labelling assay and TUNEL assay showed the suppression of apoptosis by the treatment of GLEt. Moreover, GLEt significantly increased the cellular antioxidant levels and decreased the lipid peroxides in alloxan-treated RINm5F cells. Taken together, these findings suggest that G. montanum protects pancreatic beta-cells against reactive oxygen species (ROS) by counteracting with mitochondrial membrane permeability and inhibition of the apoptotic pathway. PMID:19910683

Ramkumar, Kunga M; Lee, Ae Sin; Krishnamurthi, Kannan; Devi, Sivanesan Saravana; Chakrabarti, Tapan; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang; Lee, Nae Ho; Rajaguru, Palanisamy

2009-11-04

186

reply: Leptin and diabetes in lipoatrophic mice  

Microsoft Academic Search

Shimomura et al. reply - Human lipodystrophy (also called lipoatrophic diabetes) is genetically heterogeneous, with the severity of insulin resistance and diabetes mellitus varying widely depending on the degree of reduction in adipose tissue mass and the age of the patient. It is therefore not surprising that two mouse models of lipodystrophy (created by using two different transgenes, A-ZIP\\/F-1 and

Iichiro Shimomura; Robert E. Hammer; Shinji Ikemoto; Michael S. Brown; Joseph L. Goldstein

2000-01-01

187

RhoB Loss Prevents Streptozotocin-Induced Diabetes and Ameliorates Diabetic Complications in Mice  

PubMed Central

RhoB is an early-response gene whose expression is elevated by multiple cellular stresses; this gene plays an important role in cancer, macrophage motility, and apoptosis. These factors are essential for the onset of type 1 diabetes mellitus and related complications. This study explores the role of RhoB in ?-cell depletion and hyperglycemia-associated complications and tests whether the pleiotropic effect of statins on glycemic control is RhoB dependent. We induced ?-cell depletion in RhoB+/+, RhoB+/?, and RhoB?/? mice with streptozotocin (STZ). Diabetic status was assessed by glucose tolerance and pancreatic islet loss. RhoB?/? mice showed a significant reduction in the severity of STZ-induced diabetes; only 13% of the STZ-treated RhoB-null animals became hyperglycemic, as opposed to 61% of the wild-type controls. Diabetes-related complications, such as wound healing rate and onset of nephropathy, were also assessed. Hyperglycemic RhoB?/? mice had fewer signs of nephropathy and showed faster wound healing than RhoB+/+ animals. After assessing the diabetic status of mice treated simultaneously with STZ and simvastatin, we conclude that the effect of statins in improving glycemic control is RhoB independent. We propose that RhoB is a modifier of diabetes, important for the induction of ?-cell loss. Suppression of RhoB expression may have potential application in the treatment of diabetes and associated complications.

Bravo-Nuevo, Arturo; Sugimoto, Hikaru; Iyer, Seema; Fallon, Zachary; Lucas, Jason M.; Kazerounian, Shiva; Prendergast, George C.; Kalluri, Raghu; Shapiro, Nathan I.; Benjamin, Laura E.

2011-01-01

188

Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis  

Microsoft Academic Search

Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis.BackgroundTo elucidate the molecular mechanism of diabetic nephropathy, a high-density DNA filter array was employed to survey the gene expression profile of streptozotocin-induced diabetic CD-1 (ICR) mouse kidneys.MethodsTen-week-old CD-1 male mice were divided into four groups: (1) control, (2) unilaterally nephrectomized (UX) mice, (3) streptozotocin (STZ)-induced diabetic (STZ) mice, and (4)

Jun Wada; Hong Zhang; Yoshinori Tsuchiyama; Keita Hiragushi; Kazuyuki Hida; Kenichi Shikata; Yashpal S. Kanwar; Hirofumi Makino

2001-01-01

189

Effects of oral zinc and magnesium supplementation on serum thyroid hormone and lipid levels in experimentally induced diabetic rats  

Microsoft Academic Search

This study was designed to investigate the effects of oral zinc and magnesium supplementation on serum thyroid hormone and\\u000a lipid levels in alloxan-induced diabetic rats. Thirty-two albino male rats, weighing 234±34 g, were divided into four experimental\\u000a groups (control, diabetic, diabetic+zinc supplemented and diabetic+ magnesium supplemented). The experiment lasted for 60\\u000a d. The first 45 d of the experiment was

Burhanettin Baydas; Suzan Karagoz; Ismail Meral

2002-01-01

190

Hypoglycaemic activity of Scopariadulcis L. extract in alloxan induced hyperglycaemic rats.  

PubMed

Scoparia dulcis L. commonly known as 'Sweet Broomweed' is widely used in Indian folk medicine for the treatment of diabetes mellitus. Oral administration of 0.15, 0.30 and 0.45 g/kg body weight of the aqueous extract of the Scoparia dulcis leaves (SLEt) for 45 days resulted in a significant reduction in blood glucose, glycosylated haemoglobin and an increase in total haemoglobin but in the case of 0.45 g/kg body weight the effect was highly significant. The aqueous extract also prevented a decrease in the body weight. An oral glucose tolerance test was also performed in experimental diabetic rats, in which there was a significant improvement in glucose tolerance in animals treated with SLEt and the effect was comparable to that of glibenclamide. PMID:12410548

Pari, L; Venkateswaran, S

2002-11-01

191

Streptozotocin and alloxan induce DNA strand breaks and poly(ADP-ribose) synthetase in pancreatic islets  

Microsoft Academic Search

Streptozotocin, which produces diabetes mellitus in experimental animals1-3, has been reported to reduce the level of NAD in pancreatic islets4,5 and to inhibit islet synthesis of proinsulin6. The decrease in NAD is due to increased NAD degradation mediated by islet nuclear poly(ADP-ribose) synthetase7,8. Evidence suggests that poly(ADP-ribose) synthetase is activated when DNA is fragmented9-17. Here we describe that both Streptozotocin

Hiroshi Yamamoto; Yasuko Uchigata; Hiroshi Okamoto

1981-01-01

192

[Antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives and their nootropic action in alloxan diabetes].  

PubMed

Relationship between the antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) and their effect on conditional learning, glycemia, and lipidemia was studied in rats with alloxan-induced diabetes. In parallel, the analogous relationship was investigated for alpha-lipoic acid that is regarded as a "gold standard" in treatment of diabetic neuropathy. It was established that single administration of emoxipine and mexidol in mice in doses equivalent to therapeutic-range doses in humans produces antihypoxic effect manifested by increased resistance to acute hypoxic hypoxia in test animals. Alpha-lipoic acid is inferior to emoxipin and mexidol in the degree of antihypoxic action. Reamberin does not exhibit this effect. The introduction of emoxipin, reamberin, mexidol, and alpha-lipoic acid in rats with alloxan diabetes during 7 or 14 days in doses equivalent to therapeutic-range doses in humans corrects conditional learning disorders in direct relationship with the antihypoxic activity of these drugs. The development of the nootropic effect of emoxipin, mexidol, and alpha-lipoic acid is related to a decrease in hyperglycemia and hyperlipidemia in rats with alloxan diabetes. The nootropic action of reamberin is accompanied by a transient hypoglycemizing effect and aggravation of dyslipidemic disorders. The antihypoxic activity of investigated drugs determines the direction and expression of their lipidemic effect, but is not correlated with the hypoglycemizing action these drugs on test animals with alloxan diabetes. PMID:22379879

Volchegorski?, I A; Rassokhina, L M; Miroshnichenko, I Iu

2011-01-01

193

Sulfaphenazole treatment restores endothelium-dependent vasodilation in diabetic mice.  

PubMed

Vascular dysfunction is linked with increased free radical generation and is a major contributor to the high mortality rates observed in diabetes. Several probable sources of free radical generation have been suggested in diabetes, including cytochrome P450 (CYP) monooxygenase-dependent pathways. CYP-mediated superoxide production reduces nitric oxide (NO) bioavailability. In this study, we focus on the contribution of monooxygenase enzyme-generated reactive oxygen species in vascular dysfunction in an experimental model of diabetes mellitus type II. Diabetic male mice (db/db strain) and their age-matched controls received daily intraperitoneal injections of either the CYP 2C inhibitor sulfaphenazole (5.13 mg/kg) or saline (vehicle control) for 8 weeks. Although sulfaphenazole did not change endothelium-dependent vasodilation in control mice, it restored endothelium-mediated relaxation in db/db mice. We report for the first time that CYP 2C inhibition reduces oxidative stress (measured as plasma levels of 8-isoprostane), increases NO bioavailability (measured as NO(2)(-)) and restores endothelial function in db/db mice without affecting plasma glucose levels. Based on our findings, we speculate that inhibition of free radical generating CYP 450 monooxygenase enzymes restores endothelium-dependent vasodilation to acetylcholine. In addition, it reduces oxidative stress and increases NO bioavailability. PMID:17974492

Elmi, Shahrzad; Sallam, Nada A; Rahman, Mohammad M; Teng, Xiaowei; Hunter, Arwen L; Moien-Afshari, Farzad; Khazaei, Majid; Granville, David J; Laher, Ismail

2007-09-15

194

Effects of Ballota nigra on glucose and insulin in alloxan-diabetic albino rats.  

PubMed

The hypoglycemic effect of Ballota nigra extract on albino rats was investigated. Alloxan-induced diabetes mellitus was accompanied by several fold increases in plasma glucose. Administration of aqueous extract of B. nigra extract significantly reduced glucose in both healthy and diabetic rats. These results suggest that B. nigra possess hypoglycemic effects in rats and therefore, can be useful for the treatment of diabetes mellitus. PMID:17627273

Nusier, Mohamad K; Bataineh, Hameed N; Bataineh, Ziad M; Daradka, Haytham M

2007-08-01

195

Vanadium improves brain acetylcholinesterase activity on early stage alloxan-diabetic rats  

Microsoft Academic Search

The present study is designed to screen the possible effects of sodium orthovanadate therapy on the kinetic parameters of brain membrane-bound and soluble acetylcholinesterase (AChE) forms in alloxan-induced diabetic rats. The diabetic rats were treated with 300mg\\/kg sodium orthovanadate orally for 45 days. While diabetes significantly decreased the brain specific activity (Vmax) of AChE soluble form by 42%, it caused

Doaa A. Ghareeb; Hend M. Hussen

2008-01-01

196

The Role of Adrenomedullin in the Renal NADPH Oxidase and (Pro)renin in Diabetic Mice  

PubMed Central

Adrenomedullin has an antioxidative action and protects organs in various diseases. To clarify the role of adrenomedullin in diabetic nephropathy, we investigated the NADPH oxidase expression, renin-secreting granular cell (GC) hyperplasia, and glomerular matrix expansion in the streptozotocin (STZ)-induced diabetic adrenomedullin gene knockout (AMKO) mice compared with the STZ-diabetic wild mice at 10 weeks. The NADPH oxidase p47phox expression and lipid peroxidation products were enhanced in the glomeruli of the diabetic mice compared with that observed in the controls in both wild and AMKO mice. These changes were more obvious in the AMKO mice than in the wild mice. Glomerular mesangial matrix expansion was more severe in the diabetic AMKO mice than in the diabetic wild mice and exhibited a positive correlation with the degree of lipid peroxidation products in the glomeruli. Proteinuria was significantly higher in the diabetic AMKO mice than in the diabetic wild mice. The GC hyperplasia score and the renal prorenin expression were significantly increased in the diabetic AMKO mice than in the diabetic wild mice, and a positive correlation was observed with the NADPH oxidase expression in the macula densa. The endogenous adrenomedullin gene exhibits an antioxidant action via the inhibition of NADPH oxidase probably by suppressing the local renin-angiotensin system.

Hayashi, Michio; Fujita, Toshiro

2013-01-01

197

Hyperglycaemia potentiates the teratogenicity of retinoic acid in diabetic pregnancy in mice  

Microsoft Academic Search

Aims\\/hypothesis  We recently showed in mice that maternal diabetes increases embryonic susceptibility to caudal regression induced by vitamin A metabolite retinoic acid. Here we tested whether in the maternal diabetic milieu hyperglycaemia is the critical factor responsible for mediating this increased susceptibility.Methods  Non-diabetic pregnant mice were made hyperglycaemic by subcutaneous injections of glucose at regular intervals. Conversely, diabetic pregnant mice were treated

M. B. W. Leung; K.-W. Choy; A. J. Copp; C.-P. Pang; A. S. W. Shum

2004-01-01

198

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.

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

2009-01-01

199

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.

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

2011-01-01

200

Differential central pathology and cognitive impairment in pre-diabetic and diabetic mice.  

PubMed

Although age remains the main risk factor to suffer Alzheimer's disease (AD) and vascular dementia (VD), type 2 diabetes (T2D) has turned up as a relevant risk factor for dementia. However, the ultimate underlying mechanisms for this association remain unclear. In the present study we analyzed central nervous system (CNS) morphological and functional consequences of long-term insulin resistance and T2D in db/db mice (leptin receptor KO mice). We also included C57Bl6 mice fed with high fat diet (HFD) and a third group of C57Bl6 streptozotocin (STZ) treated mice. Db/db mice exhibited pathological characteristics that mimic both AD and VD, including age dependent cognitive deterioration, brain atrophy, increased spontaneous hemorrhages and tau phosphorylation, affecting the cortex preferentially. A similar profile was observed in STZ-induced diabetic mice. Moreover metabolic parameters, such as body weight, glucose and insulin levels are good predictors of many of these alterations in db/db mice. In addition, in HFD-induced hyperinsulinemia in C57Bl6 mice, we only observed mild CNS alterations, suggesting that central nervous system dysfunction is associated with well established T2D. Altogether our results suggest that T2D may promote many of the pathological and behavioral alterations observed in dementia, supporting that interventions devoted to control glucose homeostasis could improve dementia progress and prognosis. PMID:23790682

Ramos-Rodriguez, Juan Jose; Ortiz, Oscar; Jimenez-Palomares, Margarita; Kay, Kevin R; Berrocoso, Esther; Murillo-Carretero, Maria Isabel; Perdomo, German; Spires-Jones, Tara; Cozar-Castellano, Irene; Lechuga-Sancho, Alfonso Maria; Garcia-Alloza, Monica

2013-06-21

201

Diabetes Provides an Unfavorable Environment for Muscle Mass and Function after Muscle Injury in Mice  

Microsoft Academic Search

It is of common knowledge that diabetes decreases skeletal muscle contractility and induces atrophy. However, how hyperglycemia and insulin deficiency modify muscle mass and neuromuscular recovery after muscle injury is not well known. We have analyzed two models of diabetes: streptozotocin (STZ)-treated Swiss mice and Akita mice that spontaneously develop diabetes. A fast muscle, the tibialis anterior, was injured following

A. Vignaud; F. Ramond; C. Hourdé; A. Keller; G. Butler-Browne; A. Ferry

2007-01-01

202

Efficacy of lower doses of vanadium in restoring altered glucose metabolism and antioxidant status in diabetic rat lenses  

Microsoft Academic Search

Vanadium compounds are potent in controlling elevated blood glucose levels in experimentally induced diabetes. However the\\u000a toxicity associated with vanadium limits its role as therapeutic agent for diabetic treatment. A vanadium compound sodium\\u000a orthovanadate (SOV) was given to alloxan-induced diabetic Wistar rats in lower doses in combination withTrigonella foenum graecum, a well-known hypoglycemic agent used in traditional Indian medicines. The

Anju Preet; Bihari L. Gupta; Pramod K. Yadava; Najma Z. Baquer

2005-01-01

203

The antidiabetic effects of cysteinyl metformin, a newly synthesized agent, in alloxan- and streptozocin-induced diabetic rats  

Microsoft Academic Search

In this paper, the antidiabetic effects of cysteinyl metformin (CM), a newly synthesized agent, were investigated to evaluate the hypoglycemic\\/hypolipidemic effects by measuring blood glucose, triglyceride and insulin levels in CM- and metformin-treated diabetic rats. Two diabetic models were used: (1) an alloxan-induced model in which diabetes was produced by alloxan (200mg\\/kg, i.p.), then rats were treated with CM (300,

Zheng Liu; Jianchun Li; Zhaojun Zeng; Ming Liu; Minwei Wang

2008-01-01

204

Lipoatrophic diabetes in Irs1(-/-)/Irs3(-/-) double knockout mice.  

PubMed

Based on the phenotypes of knockout mice and cell lines, as well as pathway-specific analysis, the insulin receptor substrates IRS-1, IRS-2, IRS-3, and IRS-4 have been shown to play unique roles in insulin signal transduction. To investigate possible functional complementarity within the IRS family, we generated mice with double knockout of the genes for IRS-1/IRS-3 and IRS-1/IRS-4. Mice with a combined deficiency of IRS-1 and IRS-4 showed no differences from Irs1(-/-) mice with respect to growth and glucose homeostasis. In contrast, mice with a combined deficiency of IRS-1 and IRS-3 developed early-onset severe lipoatrophy associated with marked hyperglycemia, hyperinsulinemia, and insulin resistance. However, in contrast to other models of lipoatrophic diabetes, there was no accumulation of fat in liver or muscle. Furthermore, plasma leptin levels were markedly decreased, and adenovirus-mediated expression of leptin in liver reversed the hyperglycemia and hyperinsulinemia. The results indicate that IRS-1 and IRS-3 play important complementary roles in adipogenesis and establish the Irs1(-/-)/Irs3(-/-) double knockout mouse as a novel model of lipoatrophic diabetes. PMID:12502742

Laustsen, Palle G; Michael, M Dodson; Crute, Barbara E; Cohen, Shmuel E; Ueki, Kohjiro; Kulkarni, Rohit N; Keller, Susanna R; Lienhard, Gustav E; Kahn, C Ronald

2002-12-15

205

Regulation of urinary ACE2 in diabetic mice.  

PubMed

Angiotensin-converting enzyme-2 (ACE2) enhances the degradation of ANG II and its expression is altered in diabetic kidneys, but the regulation of this enzyme in the urine is unknown. Urinary ACE2 was studied in the db/db model of type 2 diabetes and stretozotocin (STZ)-induced type 1 diabetes during several physiological and pharmacological interventions. ACE2 activity in db/db mice was increased in the serum and to a much greater extent in the urine compared with db/m controls. Neither a specific ANG II blocker, telmisartan, nor an ACE inhibitor, captopril, altered the levels of urinary ACE2 in db/db or db/m control mice. High-salt diet (8%) increased whereas low-salt diet (0.1%) decreased urinary ACE2 activity in the urine of db/db mice. In STZ mice, urinary ACE2 was also increased, and insulin decreased it partly but significantly after several weeks of administration. The increase in urinary ACE2 activity in db/db mice reflected an increase in enzymatically active protein with two bands identified of molecular size at 110 and 75 kDa and was associated with an increase in kidney cortex ACE2 protein at 110 kDa but not at 75 kDa. ACE2 activity was increased in isolated tubular preparations but not in glomeruli from db/db mice. Administration of soluble recombinant ACE2 to db/m and db/db mice resulted in a marked increase in serum ACE2 activity, but no gain in ACE2 activity was detectable in the urine, further demonstrating that urinary ACE2 is of kidney origin. Increased urinary ACE2 was associated with more efficient degradation of exogenous ANG II (10(-9) M) in urine from db/db compared with that from db/m mice. Urinary ACE2 could be a potential biomarker of increased metabolism of ANG II in diabetic kidney disease. PMID:23761674

Wysocki, Jan; Garcia-Halpin, Laura; Ye, Minghao; Maier, Christoph; Sowers, Kurt; Burns, Kevin D; Batlle, Daniel

2013-06-12

206

BTBR Ob/Ob Mutant Mice Model Progressive Diabetic Nephropathy  

PubMed Central

There remains a need for robust mouse models of diabetic nephropathy (DN) that mimic key features of advanced human DN. The recently developed mouse strain BTBR with the ob/ob leptin-deficiency mutation develops severe type 2 diabetes, hypercholesterolemia, elevated triglycerides, and insulin resistance, but the renal phenotype has not been characterized. Here, we show that these obese, diabetic mice rapidly develop morphologic renal lesions characteristic of both early and advanced human DN. BTBR ob/ob mice developed progressive proteinuria beginning at 4 weeks. Glomerular hypertrophy and accumulation of mesangial matrix, characteristic of early DN, were present by 8 weeks, and glomerular lesions similar to those of advanced human DN were present by 20 weeks. By 22 weeks, we observed an approximately 20% increase in basement membrane thickness and a >50% increase in mesangial matrix. Diffuse mesangial sclerosis (focally approaching nodular glomerulosclerosis), focal arteriolar hyalinosis, mesangiolysis, and focal mild interstitial fibrosis were present. Loss of podocytes was present early and persisted. In summary, BTBR ob/ob mice develop a constellation of abnormalities that closely resemble advanced human DN more rapidly than most other murine models, making this strain particularly attractive for testing therapeutic interventions.

Hudkins, Kelly L.; Pichaiwong, Warangkana; Wietecha, Tomasz; Kowalewska, Jolanta; Banas, Miriam C.; Spencer, Min W.; Muhlfeld, Anja; Koelling, Mariko; Pippin, Jeffrey W.; Shankland, Stuart J.; Askari, Bardia; Rabaglia, Mary E.; Keller, Mark P.; Attie, Alan D.

2010-01-01

207

Nephrogenic diabetes insipidus in mice lacking aquaporin-3 water channels.  

PubMed

Aquaporin-3 (AQP3) is a water channel expressed at the basolateral plasma membrane of kidney collecting-duct epithelial cells. The mouse AQP3 cDNA was isolated and encodes a 292-amino acid water/glycerol-transporting glycoprotein expressed in kidney, large airways, eye, urinary bladder, skin, and gastrointestinal tract. The mouse AQP3 gene was analyzed, and AQP3 null mice were generated by targeted gene disruption. The growth and phenotype of AQP3 null mice were grossly normal except for polyuria. AQP3 deletion had little effect on AQP1 or AQP4 protein expression but decreased AQP2 protein expression particularly in renal cortex. Fluid consumption in AQP3 null mice was more than 10-fold greater than that in wild-type litter mates, and urine osmolality (<275 milliosmol) was much lower than in wild-type mice (>1,200 milliosmol). After 1-desamino-8-d-arginine-vasopressin administration or water deprivation, the AQP3 null mice were able to concentrate their urine partially to approximately 30% of that in wild-type mice. Osmotic water permeability of cortical collecting-duct basolateral membrane, measured by a spatial filtering optics method, was >3-fold reduced by AQP3 deletion. To test the hypothesis that the residual concentrating ability of AQP3 null mice was due to the inner medullary collecting-duct water channel AQP4, AQP3/AQP4 double-knockout mice were generated. The double-knockout mice had greater impairment of urinary-concentrating ability than did the AQP3 single-knockout mice. Our findings establish a form of nephrogenic diabetes insipidus produced by impaired water permeability in collecting-duct basolateral membrane. Basolateral membrane aquaporins may thus provide blood-accessible targets for drug discovery of aquaretic inhibitors. PMID:10737773

Ma, T; Song, Y; Yang, B; Gillespie, A; Carlson, E J; Epstein, C J; Verkman, A S

2000-04-11

208

Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy.  

PubMed

We investigated pregnancy-associated plasma protein-A (PAPP-A) in diabetic nephropathy. Normal human kidney showed specific staining for PAPP-A in glomeruli, and this staining was markedly increased in diabetic kidney. To assess the possible contribution of PAPP-A in the development of diabetic nephropathy, we induced diabetes with streptozotocin in 14-month-old WT and Papp-A knockout (KO) mice. Renal histopathology was evaluated after 4 months of stable hyperglycemia. Kidneys from diabetic WT mice showed multiple abnormalities including thickening of Bowman's capsule (100% of mice), increased glomerular size (80% of mice), tubule dilation (80% of mice), and mononuclear cell infiltration (90% of mice). Kidneys of age-matched non-diabetic WT mice had similar evidence of tubule dilation and mononuclear cell infiltration to those of diabetic WT mice, indicating that these changes were predominantly age-related. However, thickened Bowman's capsule and increased glomerular size appeared specific for the experimental diabetes. Kidneys from diabetic Papp-A KO mice had significantly reduced or no evidence of changes in Bowman's capsule thickening and glomerular size. There was also a shift to larger mesangial area and increased macrophage staining in diabetic WT mice compared with Papp-A KO mice. In summary, elevated PAPP-A expression in glomeruli is associated with diabetic nephropathy in humans and absence of PAPP-A is associated with resistance to the development of indicators of diabetic nephropathy in mice. These data suggest PAPP-A as a potential therapeutic target for diabetic nephropathy. PMID:23881937

Mader, Jessica R; Resch, Zachary T; McLean, Gary R; Mikkelsen, Jakob H; Oxvig, Claus; Marler, Ronald J; Conover, Cheryl A

2013-09-06

209

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

210

Insulin-tumour interrelationship in EL4 lymphoma or thymoma-bearing mice. I. Alloxan-diabetic or non-diabetic mice.  

PubMed Central

A study has been carried out in which a comparison was made between EL4 lymphoma (assumed to be an insulin-producing secreting tumour) and thymoma (an insulin-dependent tumour). Tumour development and incidence, 3H-thymidine incorporation and insulin content in tumours, the host's food intake, blood insulin, glucose and cholesterol were determined in non-diabetic and alloxan-diabetic mice. Whereas no significant differences were observed between the diabetic and non-diabetic EL4 tumour-bearing mice, the diabetic, thymoma tumour-bearing mice showed reduced tumour growth and lower tumour incidence as compared with their non-diabetic counterparts. Insulin administration to diabetic tumour bearing mice, enhanced 3H-thymidine incorporation in the thymoma tumour cells only, and the insulin content of the EL4 tumours was found to be higher than that of the thymoma tumours. Rapid diabetes remission was observed in the diabetic, EL4 tumour-bearing mice as compared with the thymoma tumour-bearing mice.

Yam, D.; Zilberstein, A.; Fink, A.; Nir, I.

1990-01-01

211

Rosiglitazone treatment improves cardiac efficiency in hearts from diabetic mice.  

PubMed

Isolated perfused hearts from type 2 diabetic (db/db) mice show impaired ventricular function, as well as altered cardiac metabolism. Assessment of the relationship between myocardial oxygen consumption (MVO(2)) and ventricular pressure-volume area (PVA) has also demonstrated reduced cardiac efficiency in db/db hearts. We hypothesized that lowering the plasma fatty acid supply and subsequent normalization of altered cardiac metabolism by chronic treatment with a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist will improve cardiac efficiency in db/db hearts. Rosiglitazone (23 mg/kg body weight/day) was administered as a food admixture to db/db mice for five weeks. Ventricular function and PVA were assessed using a miniaturized (1.4 Fr) pressure-volume catheter; MVO(2) was measured using a fibre-optic oxygen sensor. Chronic rosiglitazone treatment of db/db mice normalized plasma glucose and lipid concentrations, restored rates of cardiac glucose and fatty acid oxidation, and improved cardiac efficiency. The improved cardiac efficiency was due to a significant decrease in unloaded MVO(2), while contractile efficiency was unchanged. Rosiglitazone treatment also improved functional recovery after low-flow ischemia. In conclusion, the present study demonstrates that in vivo PPARgamma-treatment restores cardiac efficiency and improves ventricular function in perfused hearts from type 2 diabetic mice. PMID:18158644

How, O-J; Larsen, T S; Hafstad, A D; Khalid, A; Myhre, E S P; Murray, A J; Boardman, N T; Cole, M; Clarke, K; Severson, D L; Aasum, E

212

Anti-diabetic effects of lactic acid bacteria in normal and type 2 diabetic mice  

PubMed Central

The antidiabetic effects of lactic acid bacteria were investigated using mice. In Experiment 1, normal ICR mice were loaded with sucrose or starch with or without viable Lactobacillus rhamnosus GG cells. GG significantly inhibited postprandial blood glucose levels when administered with sucrose or starch. In Experiment 2, KK-Ay mice, a model of genetic type 2 diabetes, were given a basal diet containing viable GG cells or viable Lactobacillus delbrueckii subsp. bulgaricus cells for 6 weeks. Viable GG cells significantly inhibited fasting blood glucose, postprandial blood glucose in a glucose tolerance test and HbA1c. Such effects were not shown by viable L. bulgaricus cells. In Experiment 3, the KK-Ay mice were given a basal diet containing viable GG cells or heat-treated GG cells for 3 weeks. The viable GG cells significantly suppressed fasting blood glucose and impaired glucose tolerance, but the heat-treated GG showed no effects. These results demonstrated that GG decreased the postprandial blood glucose in ICR mice, and that the antidiabetic activity of lactic acid bacteria on the KK-Ay mice differed depending on the bacterial strain and whether the bacterium is viable when it arrives in the intestine. In the present study, we conclude that the antidiabetic activity may result from continuous inhibition of the postprandial blood glucose through suppression of glucose absorption from the intestine. These findings indicate that specific strains of lactic acid bacterium can be expected to be beneficial for the management of type 2 diabetes.

Honda, Kayoko; Moto, Mihoko; Uchida, Naoko; He, Fang; Hashizume, Naotaka

2012-01-01

213

Diacerhein downregulate proinflammatory cytokines expression and decrease the autoimmune diabetes frequency in nonobese diabetic (NOD) mice.  

PubMed

NOD mice are used as experimental models as they develop type 1 diabetes mellitus (DM-1) spontaneously, with a strong similarity to the human disease. Diabetes mellitus type 1 is characterized by the destruction of the islet, orchestrated by T lymphocytes that induce cytokine release like IL-1beta, promoting an inflammatory process. Diacerhein has antiinflammatory properties, inhibiting IL-1. However, the mechanisms involved in immune modulation are not completely understood. In the present study, serum and pancreatic islets were isolated to investigate the relationship between IL-1beta, IFN-gamma, IL-12 and TNF-alpha expression and diabetes onset, morphological aspects, and diacerhein dose dependence in animals treated with different doses (5, 10 and 50 mg/kg/day) and the control group (saline solution). The results demonstrated upregulation of mRNA islets and downregulation of the serum concentration of IL-1beta, IL-12 and TNF-alpha in the group treated with 5 and 10 mg/kg/day diacerhein, when compared with the saline group, and increased IFN-gamma serum concentration in the group treated with 50 mg/kg/day. These results suggest that diacerhein in NOD mice, decreases, in a dose-dependent manner, the diabetes frequency downregulating proinflammatory cytokines, such as IL-1beta, TNF-alpha, IFN-gamma and IL-12 at posttranscriptional or posttranslational level. Furthermore, using the HPLC method, diacerhein and rhein (active metabolite) were detected in serum and pancreas of treated mice. PMID:18442781

Malaguti, Carina; Vilella, Conceição Aparecida; Vieira, Karla Priscila; Souza, Gustavo H M F; Hyslop, Stephen; Zollner, Ricardo de Lima

2008-02-20

214

Trichloroethylene Does Not Accelerate Autoimmune Diabetes in NOD Mice.  

PubMed

Pre-existing or contributing risk factors, including genetic predisposition and environmental influences, are largely thought to play a crucial (though ill-elucidated) role in the development of autoimmunity. Trichloroethylene (TCE) is a widely used organic solvent, which has been suspected of increasing the prevalence of autoimmune diseases, e.g., lupus, following environmental contamination. Although few epidemiological data are available, several studies reported an accelerated and more severe disease in TCE-exposed autoimmunity-prone MRL(+/+) mice. To test whether TCE can exert similar deleterious effects on organ-specific autoimmune diseases, non obese diabetic (NOD) mice were given 5 mg/ml TCE via the drinking water for 12 weeks. TCE administration induced a decrease in CD44(+) splenic T-cells and CD45RB(high), CD54(+) blood and splenic T-cells. Conversely, the number of CD45RB(low) splenocytes was increased. Interestingly, the progressive increase in serum TNF-alpha and IFN-gamma levels normally seen with age in these mice was inhibited by TCE. There was also a relative lower incidence of histological changes in the pancreas of TCE-exposed NOD mice than in unexposed mice. Contrary to what has been found in systemic models of autoimmunity, TCE did not accelerate the diabetes of NOD mice and may have a protective effect. This finding suggests that comparative studies using different genetically related autoimmune-prone models are needed to investigate the role of xenobiotics in the precipitation of autoimmunity, particularly in sensitive populations. PMID:18958647

Ravel, Guillaume; Christ, Marielle; Perron-Lepage, Marie-France; Condevaux, Fabienne; Descotes, Jacques

2005-07-01

215

Nicotine Accelerates Angiogenesis and Wound Healing in Genetically Diabetic Mice  

PubMed Central

Recently, we have discovered an endogenous cholinergic pathway for angiogenesis mediated by endothelial nicotinic acetylcholine receptors (nAChRs). Since angiogenesis plays a major role in wound repair, we hypothesized that activation of nAChRs with nicotine would accelerate wound healing in a murine excisional wound model. In genetically diabetic and control mice full-thickness skin wounds (0.8 cm) were created on the dorsum and topically treated over 7 days with either vehicle (phosphate-buffered saline, PBS) or nicotine (10?8 mol/L, 10?9 mol/L; each, n = 5). Wound size was measured over 14 days followed by resection, histological analysis, and quantitation of vascularity. In diabetic animals an agonist (epibatidine, 10?10 mol/L) or antagonist (hexamethonium, 10?4 mol/L) of nAChRs as well as the positive control basic fibroblast growth factor (bFGF, 25 ?g/kg) were also tested. To further study the role of endothelial nAChRs in angiogenesis, we used an ex vivo vascular explant model. In diabetic mice wound healing was markedly impaired. Nicotine significantly accelerated wound healing as assessed by closure rate and histological score. The effects of nicotine were equal to bFGF and were mimicked by epibatidine and blocked by hexamethonium. Histomorphometry revealed increased neovascularization in animals treated with nicotine. Furthermore, capillary-like sprouting from vascular explants was significantly enhanced by nicotine. In conclusion, agonist-induced stimulation of nAChRs accelerates wound healing in diabetic mice by promoting angiogenesis. We have discovered a cholinergic pathway for angiogenesis that is involved in wound healing, and which is a potential target for therapeutic angiogenesis.

Jacobi, Johannes; Jang, James J.; Sundram, Uma; Dayoub, Hayan; Fajardo, Luis F.; Cooke, John P.

2002-01-01

216

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

217

Mitochondrial redox studies of oxidative stress in kidneys from diabetic mice  

PubMed Central

Chronic hyperglycemia during diabetes leads to increased production of reactive oxygen species (ROS) and increased oxidative stress (OS). Here we investigated whether changes in the metabolic state can be used as a marker of OS progression in kidneys. We examined redox states of kidneys from diabetic mice, Akita/+ and Akita/+;TSP1–/– mice (Akita mice lacking thrombospondin-1, TSP1) with increasing duration of diabetes. OS as measured by mitochondrial redox ratio (NADH/FAD) was detectable shortly after the onset of diabetes and further increased with the duration of diabetes. Thus, cryo fluorescence redox imaging was used as a quantitative marker of OS progression in kidneys from diabetic mice and demonstrated that alterations in the oxidative state of kidneys occur during the early stages of diabetes.

Maleki, Sepideh; Sepehr, Reyhaneh; Staniszewski, Kevin; Sheibani, Nader; Sorenson, Christine M.; Ranji, Mahsa

2012-01-01

218

The postnatal maternal environment influences diabetes development in nonobese diabetic mice  

PubMed Central

When nonobese-diabetic (NOD) mouse embryos were implanted into pseudopregnant mothers of a nonautoimmune mouse strain, the progeny had a reduced type 1 diabetes (T1D) incidence, suggesting that transmission of maternal autoantibodies is important for T1D development. Whether eliminating islet autoantibody transmission in utero, or postnatally (through milk), prevented T1D is unknown. Herein, we show that fostering newborn NOD mice on B-cell deficient NOD.Ig??/? dams does not prevent T1D, demonstrating that postnatally transmitted islet autoantibodies are not required for disease pathogenesis. Additionally, NOD.Ig??/? mice reared on NOD dams did not develop T1D, indicating that autoantibody transmission to B-cell deficient NOD neonates is insufficient to trigger T1D. Interestingly, newborn NOD mice that were reared by ICR (but not NOD or C57BL/6) dams had reduced T1D incidence, although not as reduced as that reported after embryo transfer to ICR mice, suggesting that both prenatal and postnatal factors contribute to the observed reduction in T1D incidence. Thus, NOD mice have different risks for developing T1D depending on the strain of their foster mother, and both prenatal and postnatal maternal factors, other than islet autoantibodies, influence their T1D incidence. The results may be relevant for understanding the increasing incidence of T1D and designing interventions.

Washburn, L.R.; Dang, H.; Tian, J.; Kaufman, D.L.

2007-01-01

219

Evaluation of venlafaxine on glucose homeostasis and oxidative stress in diabetic mice.  

PubMed

Depression occurs frequently with diabetes affecting the quality of life. All major classes of antidepressants have been shown to have a direct pharmacologic effect on metabolic function, which further worsens glycemic control. There were no reports on the effects of venlafaxine on glucose levels and oxidative stress in diabetic animals. The present study evaluated the effects of venlafaxine (8 and 16 mg/kg per d) on glucose homeostasis along with oxidative stress in brain in diabetic mice (streptozotocin (STZ), 40 mg/kg per d for 5 days). We observed that 21 days of administration of venlafaxine (8 and 16 mg/kg per d) in diabetic mice significantly enhanced swimming in normal and STZ-treated mice with a corresponding reduction in immobility. No significant difference in blood glucose levels was observed in diabetic and normal mice following venlafaxine treatment. Venlafaxine (16 mg/kg) reversed STZ-induced elevated thiobarbituric acid reactive substance (TBARS) levels and also restored the glutathione (GSH) levels in diabetic mice. Venlafaxine (8 and 16 mg/kg) per se does not produce any significant effect in normal animals. The results indicate a dose-dependent antidepressant action of venlafaxine in diabetes-induced depressive mice. Furthermore, the blood glucose levels were not significantly altered in normal and diabetic mice. In addition, venlafaxine exhibited a decrease in TBARS and elevation in GSH levels in mice brain. Venlafaxine drug treatment appears to be safer for depression associated with diabetes. PMID:22751285

Khanam, R; Najfi, H; Akhtar, M; Vohora, D

2012-07-02

220

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

221

Validation of structural and functional lesions of diabetic retinopathy in mice  

PubMed Central

Diabetic retinopathy is a serious long-term complication of diabetes mellitus. There is considerable interest in using mouse models, which can be genetically modified, to understand how retinopathy develops and can be inhibited. Not all retinal lesions that develop in diabetic patients have been reproduced in diabetic mice; conversely, not all abnormalities found in diabetic mice have been studied or identified in diabetic patients. Thus, it is important to recognize which structural and functional abnormalities that develop in diabetic mice have been validated against the lesions that characteristically develop in diabetic patients. Those lesions that have been observed to develop in the mouse models to date are predominantly characteristic of the early stages of retinopathy. Identification of new therapeutic ways to inhibit these early lesions is expected to help inhibit progression to more advanced and clinically important stages of retinopathy.

Tang, J.; Berkowitz, B.A.

2010-01-01

222

Increased atherosclerosis in streptozotocin-induced diabetic mice.  

PubMed Central

Premature and extensive atheroscleroses involving renal, peripheral, and cardiovascular sites remain major complications of diabetes mellitus. Controversy exists as to the contribution of hyperglycemia versus elevated local or systemic concentrations of insulin to atherosclerosis risk. In this report, we developed the first murine model susceptible to both atherosclerosis and diabetes to determine which diabetogenic factors contribute to vascular disease. C57BL/6 and BALB/c mice were treated with multiple low-dose streptozotocin (STZ) or control citrate buffer and fed rodent chow or an atherogenic-promoting (Ath) diet for 12-20 wk. STZ treatment resulted in sustained hyperglycemia (250-420 mg/dl) and a modest reduction in plasma insulin levels for both strains regardless of diet. Citrate-treated C57BL/6 mice fed the Ath diet showed extensive oil red O-staining fatty streak aortic sinus lesions (20,537+/-2,957 micron2), the size of which did not differ for Ath-fed mice treated with STZ (16,836+/-2,136 micron2). In contrast, hyperglycemic BALB/c mice fed the Ath diet showed a 17-fold increase in atherosclerotic lesion area (7,922+/-2,096 micron2) as compared with citrate-treated mice fed the Ath diet (467+/-318 micron2). Correlations between lesion size and plasma glucose levels were significant for BALB/c (r = 0.741, P < 0.009), but not C57BL/6 (r = 0.314, P<0.3) mice. Lesion size correlated significantly with plasma cholesterol for C57BL/6 (r = 0.612, P<0.03) but not BALB/c (r = 0.630, P<0.1) mice. Immunohistochemistry showed that aortic sinus lesions from both strains contained macrophages, but smooth muscle cells were clearly present in lesions of BALB/c mice. In summary, we present the first small animal model showing accelerated atherosclerosis in response to hyperglycemia. Fatty streaks resembled those of human type II lesions in that both macrophages and smooth muscle cells were evident. In addition, our results support the concept that hyperglycemia as opposed to hyperinsulinemia contributes heavily to risk of atherosclerosis.

Kunjathoor, V V; Wilson, D L; LeBoeuf, R C

1996-01-01

223

AGE/RAGE produces endothelial dysfunction in coronary arterioles in type 2 diabetic mice.  

PubMed

We hypothesized that impaired nitric oxide (NO)-dependent dilation (endothelial dysfunction) in type 2 diabetes results, in part, from elevated production of superoxide (O(2)(*-)) induced by the interaction of advanced glycation end products (AGE)/receptor for AGE (RAGE) and TNF-alpha signaling. We assessed the role of AGE/RAGE and TNF-alpha signaling in endothelial dysfunction in type 2 diabetic (Lepr(db)) mice by evaluation of endothelial function in isolated coronary resistance vessels of normal control (nondiabetic, m Lepr(db)) and diabetic mice. Although dilation of vessels to the endothelium-independent vasodilator sodium nitroprusside (SNP) was not different between diabetic and control mice, dilation to the endothelium-dependent agonist acetylcholine (ACh) was reduced in diabetic vs. control mice. The activation of RAGE with RAGE agonist S100b eliminated SNP-potentiated dilation to ACh in Lepr(db) mice. Administration of a soluble form of RAGE (sRAGE) partially restored dilation in diabetic mice but did not affect dilation in control mice. The expression of RAGE in coronary arterioles was markedly increased in diabetic vs. control mice. We also observed in diabetic mice that augmented RAGE signaling augmented expression of TNF-alpha, because this increase was attenuated by sRAGE or NF-kappaB inhibitor MG132. Protein and mRNA expression of NAD(P)H oxidase subunits including NOX-2, p22(phox), and p40(phox) increased in diabetic compared with control mice. sRAGE significantly inhibited the expression of NAD(P)H oxidase in diabetic mice. These results indicate that AGE/RAGE signaling plays a pivotal role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes. PMID:18539754

Gao, Xue; Zhang, Hanrui; Schmidt, Ann Marie; Zhang, Cuihua

2008-06-06

224

AGE/RAGE produces endothelial dysfunction in coronary arterioles in Type 2 diabetic mice  

PubMed Central

We hypothesized that impaired nitric oxide (NO)-dependent dilation (endothelial dysfunction) in Type 2 diabetes results, in part, from elevated production of superoxide (O2•?) induced by the interaction of advanced glycation end products (AGE)/receptor for AGE (RAGE) and TNF-? signaling. We assessed the role of AGE/RAGE and TNF-? signaling in endothelial dysfunction in Type 2 diabetic (Leprdb) mice by evaluation of endothelial function in isolated coronary resistance vessels of normal control (nondiabetic, m Leprdb) and diabetic mice. Although dilation of vessels to the endothelium-independent vasodilator sodium nitroprusside (SNP) was not different between diabetic and control mice, dilation to the endothelium-dependent agonist acetylcholine (ACh) was reduced in diabetic vs. control mice. The activation of RAGE with RAGE agonist S100b eliminated SNP-potentiated dilation to ACh in Leprdb mice. Administration of a soluble form of RAGE (sRAGE) partially restored dilation in diabetic mice but did not affect dilation in control mice. The expression of RAGE in coronary arterioles was markedly increased in diabetic vs. control mice. We also observed in diabetic mice that augmented RAGE signaling augmented expression of TNF-?, because this increase was attenuated by sRAGE or NF-?B inhibitor MG132. Protein and mRNA expression of NAD(P)H oxidase subunits including NOX-2, p22phox, and p40phox increased in diabetic compared with control mice. sRAGE significantly inhibited the expression of NAD(P)H oxidase in diabetic mice. These results indicate that AGE/RAGE signaling plays a pivotal role in regulating the production/expression of TNF-?, oxidative stress, and endothelial dysfunction in Type 2 diabetes.

Gao, Xue; Zhang, Hanrui; Schmidt, Ann Marie; Zhang, Cuihua

2008-01-01

225

Cardiovascular and autonomic phenotype of db/db diabetic mice  

PubMed Central

SUMMARY The db/db mice serve as a good model for type 2 diabetes, characterized by hyperinsulinemia and progressive hyperglycemia. There are limited and conflicting data on the cardiovascular changes in this model. The aim was to characterize the cardiovascular/autonomic phenotype of male db/db mice and evaluate the role of angiotensin (Ang) AT1 receptors. Radiotelemetry was used to monitor 24 hr blood pressure (BP) in mice for 8 weeks. Parameters measured were mean arterial pressure (MAP), heart rate (HR) and their variabilities. MAP and BP circadian rhythms were not altered in 8 wk db/db while HR and locomotor activity were decreased. With aging, MAP gradually increased in db/db mice and the 12-h light values did not dip significantly from the 12-h dark periods. In 14 wk mice, MAP was increased during light (101 ± 1 vs. 117 ± 2 mmHg, p < 0.01; Control vs. db/db) and dark phases (110 ± 1.7 vs. 121 ± 3.1 mmHg, p<0.01; Control vs. db/db). This increase in BP was associated with significant increase in plasma ACE activity and Ang II levels. Chronic treatment with losartan (10 mg/kg/day) blocked the increase in MAP in db/db with no effect in controls. Spectral analysis was used to monitor autonomic cardiovascular function. The circadian rhythm observed in SAP variance and its LF component in control mice was absent in db/db. There were no changes in HR variability and spontaneous baroreflex sensitivity between control and db/db mice. Results document an age related increase in MAP in db/db reduced by antagonism of Ang AT1 receptors and alterations in autonomic balance and components of the renin angiotensin system.

Senador, Danielle; Kanakamedala, Keerthy; Irigoyen, Maria Claudia; Morris, Mariana; Elased, Khalid. M.

2011-01-01

226

Co-Therapy Using Lytic Bacteriophage and Linezolid: Effective Treatment in Eliminating Methicillin Resistant Staphylococcus aureus (MRSA) from Diabetic Foot Infections  

PubMed Central

Background Staphylococcus aureus remains the predominant pathogen in diabetic foot infections and prevalence of methicillin resistant S.aureus (MRSA) strains further complicates the situation. The incidence of MRSA in infected foot ulcers is 15–30% and there is an alarming trend for its increase in many countries. Diabetes acts as an immunosuppressive state decreasing the overall immune functioning of body and to worsen the situation, wounds inflicted with drug resistant strains represent a morbid combination in diabetic patients. Foot infections caused by MRSA are associated with an increased risk of amputations, increased hospital stay, increased expenses and higher infection-related mortality. Hence, newer, safer and effective treatment strategies are required for treating MRSA mediated diabetic foot infections. The present study focuses on the use of lytic bacteriophage in combination with linezolid as an effective treatment strategy against foot infection in diabetic population. Methodology Acute hindpaw infection with S.aureus ATCC 43300 was established in alloxan induced diabetic BALB/c mice. Therapeutic efficacy of a well characterized broad host range lytic bacteriophage, MR-10 was evaluated alone as well as in combination with linezolid in resolving the course of hindpaw foot infection in diabetic mice. The process of wound healing was also investigated. Results and Conclusions A single administration of phage exhibited efficacy similar to linezolid in resolving the course of hindpaw infection in diabetic animals. However, combination therapy using both the agents was much more effective in arresting the entire infection process (bacterial load, lesion score, foot myeloperoxidase activity and histopathological analysis). The entire process of tissue healing was also hastened. Use of combined agents has been known to decrease the frequency of emergence of resistant mutants, hence this approach can serve as an effective strategy in treating MRSA mediated foot infections in diabetic individuals who do not respond to conventional antibiotic therapy.

Chhibber, Sanjay; Kaur, Tarsem; Sandeep Kaur

2013-01-01

227

Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice  

PubMed Central

The recent development of small-molecule tyrosine kinase (TK) inhibitors offers increasing opportunities for the treatment of autoimmune diseases. In this study, we investigated the potential of this new class of drugs to treat and cure type 1 diabetes (T1D) in the NOD mouse. Treatment of prediabetic and new onset diabetic mice with imatinib (Gleevec) prevented and reversed T1D. Similar results were observed with sunitinib (Sutent), an additional approved multikinase inhibitor, suggesting that the primary target of imatinib, c-Abl, was not essential in blocking disease in this model. Additional studies with another TK inhibitor, PLX647 (targeting c-Kit and c-Fms) or an anti-c-Kit mAb showed only marginal efficacy whereas a soluble form of platelet-derived growth factor receptor (PDGFR), PDGFR?Ig, rapidly reversed diabetes. These findings strongly suggest that inhibition of PDGFR is critical to reverse diabetes and highlight a crucial role of inflammation in the development of T1D. These conclusions were supported by the finding that the adaptive immune system was not significantly affected by imatinib treatment. Finally, and most significantly, imatinib treatment led to durable remission after discontinuation of therapy at 10 weeks in a majority of mice. Thus, long-term efficacy and tolerance is likely to depend on inhibiting a combination of tyrosine kinases supporting the use of selective kinase inhibitors as a new, potentially very attractive approach for the treatment of T1D.

Louvet, Cedric; Szot, Gregory L.; Lang, Jiena; Lee, Michael R.; Martinier, Nicolas; Bollag, Gideon; Zhu, Shirley; Weiss, Arthur; Bluestone, Jeffrey A.

2008-01-01

228

Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice.  

PubMed

Twelve plants used for the traditional treatment of diabetes mellitus in northern Europe were studied using normal and streptozotocin diabetic mice to evaluate effects on glucose homeostasis. The plants were administered in the diet (6.25% by weight) and/or as decoctions or infusions in place of drinking water, to coincide with the traditional method of preparation. Treatment for 28 days with preparations of burdock (Arctium lappa), cashew (Anacardium occidentale), dandelion (Taraxacum officinale), elder (Sambucus nigra), fenugreek (Trigonella foenum-graecum), guayusa (Ilex guayusa), hop (Humulus lupulus), nettle (Urtica dioica), cultivated mushroom (Agaricus bisporus), periwinkle (Catharanthus roseus), sage (Salvia officinale), and wild carrot (Daucus carrota) did not affect the parameters of glucose homeostasis examined in normal mice (basal plasma glucose and insulin, glucose tolerance, insulin-induced hypoglycaemia and glycated haemoglobin). After administration of streptozotocin (200 mg/kg) burdock and nettle aggravated the diabetic condition, while cashew, dandelion, elder, fenugreek, hop, periwinkle, sage and wild carrot did not significantly affect the parameters of glucose homeostasis studied (basal glucose and insulin, insulin-induced hypoglycaemia, glycated haemoglobin and pancreatic insulin concentration). Guayusa and mushroom retarded the development of hyperglycaemia in streptozotocin diabetes and reduced the hyperphagia, polydipsia, body weight loss, and glycated haemoglobin. Mushroom also countered the initial reduction in plasma insulin and the reduction in pancreatic insulin concentration, and improved the hypoglycaemic effect of exogenous insulin. These studies suggest the presence of potentially useful antidiabetic agents in guayusa and mushroom. PMID:2743711

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

1989-02-01

229

Renal protective effect of xiao-chai-hu-tang on diabetic nephropathy of type 1-diabetic mice.  

PubMed

Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese medicine formula consisting of seven medicinal plants, is used in the treatment of various diseases. We show here that XCHT could protect type-1 diabetic mice against diabetic nephropathy, using streptozotocin (STZ)-induced diabetic mice and high-glucose (HG)-exposed rat mesangial cell (RMC) as models. Following 4 weeks of oral administration with XCHT, renal functions and renal hypertrophy significantly improved in the STZ-diabetic mice, while serum glucose was only moderately reduced compared to vehicle treatment. Treatment with XCHT in the STZ-diabetic mice and HG-exposed RMC resulted in a decrease in expression levels of TGF-?1, fibronectin, and collagen IV, with concomitant increase in BMP-7 expression. Data from DPPH assay, DHE stain, and CM-H(2)DCFDA analysis indicated that XCHT could scavenge free radicals and inhibit high-glucose-induced ROS in RMCs. Taken together, these results suggest that treatment with XCHT can improve renal functions in STZ-diabetic mice, an effect that is potentially mediated through decreasing oxidative stress and production of TGF-?1, fibronectin, and collagen IV in the kidney during development of diabetic nephropathy. XCHT, therefore merits further investigation for application to improve renal functions in diabetic disorders. PMID:22474533

Lin, Chun-Ching; Lin, Liang-Tzung; Yen, Ming-Hong; Cheng, Juei-Tang; Hsing, Chung-Hsi; Yeh, Ching-Hua

2012-03-07

230

Increased inner ear susceptibility to noise injury in mice with streptozotocin-induced diabetes.  

PubMed

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

2012-07-30

231

Increased degradation of dermal collagen in diabetic rats.  

PubMed

The effect of alloxan induced diabetes on the dermal collagen content of albino rats was studied in relation to few lysosomal enzymes. Diabetes decreased the dermal collagen content. The specific activities of the lysosomal enzymes studied in the diabetic rat skin were elevated. It has been established that lysosomal enzymes degrade the connective tissue components. Thus, it may be suggested that the increase in the lysosomal enzymes studied should have facilitated the decrease in dermal collagen content of diabetic rats by increasing the degradation of dermal collagen. PMID:1816088

Rajkumar, L; Srinivasan, N; Balasubramanian, K; Govindarajulu, P

1991-11-01

232

Disturbance of methyl group metabolism in alloxan-diabetic sheep.  

PubMed

Alloxan-induced diabetes results in changes in the activities of a number of enzymes related to methyl group metabolism in sheep. Decreases in the activities of phospholipid methyltransferase and betaine-homocysteine methyltransferase in diabetic sheep liver indicate a reduced rate of choline synthesis and oxidation. A 65-fold increase in the activity of glycine methyltransferase and a 4-fold rise in the activity of gamma-cystathionase in diabetic sheep liver with elevated urinary excretion of cyst(e)ine suggest that catabolism of the methyl group of methionine and homocysteine was enhanced in the diabetic state. PMID:4038311

Xue, G P; Snoswell, A M

1985-06-01

233

Amelioration in wound healing in diabetic toll-like receptor-4 knockout mice.  

PubMed

Toll-like receptor-4 (TLR4) is a sentinel pathogen recognition receptor with a pivotal role in inflammation, tissue injury, diabetes and its complications. The aim of the study was to examine the contribution of TLR4 expression and activation to the prolonged inflammation observed in diabetic wounds. Diabetes was induced in male C57BL/6J and TLR4 knockout (KO) mice using streptozotocin (STZ) with matching non-diabetic mice as control. After 2weeks of persistent hyperglycemia in the mice, full-thickness excision wounds were made on the backs aseptically. Total RNA and protein were subjected to real-time PCR and western blot analyses. Wound sizes were measured using digital planimetry. TLR4 mRNA and protein expression increased significantly in wounds of diabetic mice compared with non-diabetic mice (P<0.05). IL-6, TNF-? concentration and nuclear factor-?B (NF-?B) activation were increased in diabetic wounds compared to non-diabetic wounds and knockout of TLR4 alleviates wound healing and decreases inflammation in diabetic TLR4 KO mice. Collectively, our findings show that increased TLR4 mRNA and protein expression and activation contribute to the prolonged inflammation in the diabetic wounds and that absence of TLR4 may result in decreased inflammation and improved wound healing. PMID:23773694

Dasu, Mohan R; Jialal, Ishwarlal

2013-06-15

234

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

235

Myocardial adipose triglyceride lipase overexpression protects diabetic mice from the development of lipotoxic cardiomyopathy.  

PubMed

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

2013-01-24

236

Anti-diabetic effects of lactic acid bacteria in normal and type 2 diabetic mice.  

PubMed

The antidiabetic effects of lactic acid bacteria were investigated using mice. In Experiment 1, normal ICR mice were loaded with sucrose or starch with or without viable Lactobacillus rhamnosus GG cells. GG significantly inhibited postprandial blood glucose levels when administered with sucrose or starch. In Experiment 2, KK-A(y) mice, a model of genetic type 2 diabetes, were given a basal diet containing viable GG cells or viable Lactobacillus delbrueckii subsp. bulgaricus cells for 6 weeks. Viable GG cells significantly inhibited fasting blood glucose, postprandial blood glucose in a glucose tolerance test and HbA1c. Such effects were not shown by viable L. bulgaricus cells. In Experiment 3, the KK-A(y) mice were given a basal diet containing viable GG cells or heat-treated GG cells for 3 weeks. The viable GG cells significantly suppressed fasting blood glucose and impaired glucose tolerance, but the heat-treated GG showed no effects. These results demonstrated that GG decreased the postprandial blood glucose in ICR mice, and that the antidiabetic activity of lactic acid bacteria on the KK-A(y) mice differed depending on the bacterial strain and whether the bacterium is viable when it arrives in the intestine. In the present study, we conclude that the antidiabetic activity may result from continuous inhibition of the postprandial blood glucose through suppression of glucose absorption from the intestine. These findings indicate that specific strains of lactic acid bacterium can be expected to be beneficial for the management of type 2 diabetes. PMID:22962525

Honda, Kayoko; Moto, Mihoko; Uchida, Naoko; He, Fang; Hashizume, Naotaka

2012-07-30

237

The association between spontaneous pyelonephritis and maturity-onset diabetes mellitus in male MM mice  

Microsoft Academic Search

Summary Blood glucose and glucose tolerance tests demonstrated that many male MM mice are diabetic. Serial urine sampling showed that the diabetes occurred only in mature MM males and consisted of a single self-limiting episode. Histological examination of the pancreas, together with measurements of body weight, glycosylated haemoglobin and plasma insulin, revealed that the diabetes was of the maturity- onset

D. M. Taylor; D. L. Neal; P. A. McBride

1987-01-01

238

Apelin modulates aortic vascular tone via endothelial nitric oxide synthase phosphorylation pathway in diabetic mice  

Microsoft Academic Search

Objective: The apelin receptor APJ is a putative receptor protein related to angiotensin (Ang) type 1 receptor. The apelin-APJ system has been implicated in diabetes, but its role in the diabetic vasculature and the mechanisms involved remain unclear. Our aim here was to explore the regulatory role of apelin in the aortic vascular tone in diabetic mice. Methods: A Multi

Jiu-Chang Zhong; Xi-Yong Yu; Yu Huang; Lai-Ming Yung; Chi-Wai Lau; Shu-Guang Lin

2007-01-01

239

Characteristics of the Epidermis and Stratum Corneum of Hairless Mice with Experimentally Induced Diabetes Mellitus  

Microsoft Academic Search

Diabetes mellitus induces many pathophysiologic changes in the skin. Even so, dermatologists still lack an animal model of diabetes that enables the direct evaluation of the various functional properties of the skin. Our group induced two types of an experimental type 1 diabetes model in hairless mice by administering either streptozotocin or alloxan, in order to examine the properties of

Shingo Sakai; Yoko Endo; Naoko Ozawa; Tomoko Sugawara; Ayumi Kusaka; Tetsuya Sayo; Hachiro Tagami; Shintaro Inoue

2003-01-01

240

Metabolic profile changes in the testes of mice with streptozotocin-induced type 1 diabetes mellitus  

Microsoft Academic Search

Summary Contrary to the traditional view, recent studies suggest that diabetes mellitus has an adverse influence on male reproductive function. Our aim was to deter- mine the effect of diabetes on the testicular environment by identifying and then assessing perturbations in small molecule metabolites. Testes were obtained from control and streptozotocin-induced diabetic C57BL ?6 mice, 2, 4 and 8 weeks

C. Mallidis; B. D. Green; D. Rogers; I. M. Agbaje; J. Hollis; M. Migaud; E. Amigues; N. McClure; R. A. Browne

2009-01-01

241

Antihyperlipidaemic effect of Gymnema montanum: a study on lipid profile and fatty acid composition in experimental diabetes.  

PubMed

In the present study, the antihyperlipidaemic efficacy of ethanol extract of Gymnema montanum leaves was investigated in alloxan-induced diabetic rats and the effect was compared to standard hypoglycaemic drug, glibenclamide. Male adult albino Wistar rats were injected with freshly prepared solution of alloxan monohydrate (150 mg/kg body weight) to induce diabetes. After 2 weeks, the rats with moderate diabetes were administered G. montanum leaves (200 mg/kg body weight) for 21 days by gastric lavage, after which serum, liver and kidney samples were analysed for lipid profile, lipoprotein changes and fatty acid composition. While the alloxan-induced diabetic rats showed a significant increase in the levels of cholesterol, triglycerides and free fatty acids, the levels in the animals treated with G. montanum leaves were considerably reduced and restored to near normal values. Antihyperlipidaemic effects of G. montanum leaves were found to be comparable with that of glibenclamide. Similarly, G. montanum leaves treatment resulted in reversal of alterations observed in the plasma lipoproteins (high-density lipoprotein, low-density lipoprotein and very high-density lipoprotein-cholesterol) and fatty acid composition in serum, liver and kidney of alloxan-induced rats. Our study suggests that phytochemicals present in G. montanum may play an important role in suppressing the elevated lipid profile in diabetes and may be useful for the prevention and/or early treatment of diabetes-associated hyperlipidaemia. PMID:19067681

Ramkumar, Kunga Mohan; Vijayakumar, Ramasamy Subramaniam; Ponmanickam, Ponnirul; Velayuthaprabhu, Shanmugan; Archunan, Govindaraju; Rajaguru, Palanisamy

2008-12-01

242

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

Microsoft Academic Search

Previously, we found that bis(allixinato)oxovanadium(IV) (VO(alx)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)2 was further tested in type 2 diabetes with low insulin sensitivity. The effect of oral administration of VO(alx)2 was examined in obesity-linked type

Yusuke Adachi; Yutaka Yoshikawa; Jiro Yoshida; Yukihiro. Kodera; Akira. Katoh; Jitsuya. Takada; Hiromu. Sakurai

2006-01-01

243

AT1-receptor-deficiency induced atheroprotection in diabetic mice is partially mediated via PPAR?  

PubMed Central

Objective Peroxisome-proliferator–activated-receptor-? (PPAR?) acts as a transcriptional regulator of multiple genes involved in glucose and lipid metabolism. In vitro studies showed that activated PPAR? suppresses AT1R-gene expression and vice versa. However, it has not yet been determined in vivo, whether AT1R-PPAR?-interactions play a relevant role in the pathogenesis of diabetic complications and specifically in accelerated atherosclerosis. Methods and results ApoE?/? and ApoE?/?/AT1R?/?-mice were rendered diabetic by intraperitoneal injections of streptozotocin. Diabetic and non-diabetic ApoE?/?-mice were further randomized to receive the AT1R antagonist telmisartan, the selective PPAR? antagonist GW9662, telmisartan and GW9662 or vehicle for 18 weeks. Diabetic and non-diabetic ApoE?/?/AT1R?/?-mice were randomized to receive either GW9662 or vehicle. GW9662 treatment in diabetic ApoE?/? and diabetic ApoE?/?/AT1?/?-mice resulted in the highest elevation of fasting blood glucose levels, whereas telmisartan treatment and AT1 deficiency in ApoE?/?-mice showed the lowest fasting blood glucose levels. Diabetic ApoE?/?-mice displayed severe impairment of endothelial function, enhanced oxidative stress and increased atherosclerotic lesion formation. ApoE?/?/AT1R?/? and telmisartan-treated ApoE?/?-mice showed a significantly better endothelial function, decreased oxidative stress and reduced atherosclerotic lesion formation. Treatment of diabetic ApoE?/? and ApoE?/?/AT1R?/?-mice with the selective PPAR? antagonist GW9662 omitted the atheroprotective effects of AT1R deficiency or AT1 antagonism. Conclusion Genetic disruption or pharmacological inhibition of the AT1R attenuates atherosclerosis and improves endothelial function in diabetic ApoE?/?-mice via the PPAR? pathway.

2013-01-01

244

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.

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

2011-01-01

245

Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice  

PubMed Central

Amputation as a result of impaired wound healing is a serious complication of diabetes. Inadequate angiogenesis contributes to poor wound healing in diabetic patients. Endothelial progenitor cells (EPCs) normally augment angiogenesis and wound repair but are functionally impaired in diabetics. Here we report that decreased expression of manganese superoxide dismutase (MnSOD) in EPCs contributes to impaired would healing in a mouse model of type 2 diabetes. A decreased frequency of circulating EPCs was detected in type 2 diabetic (db/db) mice, and when isolated, these cells exhibited decreased expression and activity of MnSOD. Wound healing and angiogenesis were markedly delayed in diabetic mice compared with normal controls. For cell therapy, topical transplantation of EPCs onto excisional wounds in diabetic mice demonstrated that diabetic EPCs were less effective than normal EPCs at accelerating wound closure. Transplantation of diabetic EPCs after MnSOD gene therapy restored their ability to mediate angiogenesis and wound repair. Conversely, siRNA-mediated knockdown of MnSOD in normal EPCs reduced their activity in diabetic wound healing assays. Increasing the number of transplanted diabetic EPCs also improved the rate of wound closure. Our findings demonstrate that cell therapy using diabetic EPCs after ex vivo MnSOD gene transfer accelerates their ability to heal wounds in a mouse model of type 2 diabetes.

Marrotte, Eric J.; Chen, Dan-Dan; Hakim, Jeffrey S.; Chen, Alex F.

2010-01-01

246

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.

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

2010-01-01

247

Type 2 diabetes mellitus in mice aggravates the renal impact of hemorrhagic shock.  

PubMed

The objectives of this study were to determine whether type 2 diabetic mice would exhibit a more severe renal impact of hemorrhagic shock (HS) based on a recently described model of acute kidney injury and to determine the impact of HS on renal responses to hypoxia. We induced HS or sham procedure in type 2 diabetic and obese db/db mice. Creatininemia, glomerular filtration rate, urine output, histologic injury score, and kidney inductible molecule 1 mRNA were used to investigate the renal impact of HS. Tissular hypoxia and its impact were quantified using pimonidazole immunostaining and mRNA of hypoxic inducible factor, vascular endothelial growth factor receptors 1 and 2, Tie-2, endothelial nitric oxide synthase, and inducible nitric oxide synthase. Diabetic mice exhibiting mild diabetic nephropathy express hypoxic signals at baseline. The renal impact of HS was more severe in diabetic mice, with a worsening of tissular hypoxia and an altered response to hypoxia. Furthermore, endothelial nitric oxide synthase was highly overexpressed in diabetic shocked mice when compared with nondiabetic shocked mice. Renal impact of HS in type 2 diabetic mice is more intense than in nondiabetic ones. Preexisting hypoxia during diabetes could result in a renal preconditioning that modifies endothelial and tissular responses to acute kidney injury. PMID:22814286

Dupuy, Virginie; Mayeur, Nicolas; Buléon, Marie; Jaafar, Acil; Al Saati, Talal; Schaak, Stéphane; Praddaude, Françoise; Minville, Vincent; Tack, Ivan

2012-10-01

248

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

PubMed

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

2010-05-26

249

Alterations in the Secretory Response of Non-obese Diabetic (NOD) Mice to Muscarinic Receptor Stimulation  

Microsoft Academic Search

Salivary gland secretion in non-obese diabetic (NOD) and BALB\\/c mice was evaluated following stimulation with the muscarinic receptor agonist pilocarpine. Both saliva flow rates and total protein were similar in BALB\\/c and prediabetic NOD mice. With diabetes onset in NOD mice, the saliva flow rate and protein concentration were dramatically reduced. The level of cyclic AMP (cAMP) generated 10 min

Hideo Yamamoto; Nina E. Sims; Shawn P. Macauley; Kim-Hoa T. Nguyen; Yoichi Nakagawa; Michael G. Humphreys-Beher

1996-01-01

250

Monocyte chemoattractant protein-1 promotes the development of diabetic renal injury in streptozotocin-treated mice  

Microsoft Academic Search

Diabetic nephropathy involves a renal inflammatory response induced by the diabetic milieu. Macrophages accumulate in diabetic kidneys in association with the local upregulation of monocyte chemoattractant protein-1 (MCP-1); however, the contribution of macrophages to renal injury and the importance of MCP-1 to their accrual are unclear. Therefore, we examined the progression of streptozotocin (STZ)-induced diabetic nephropathy in mice deficient in

F Y Chow; D J Nikolic-Paterson; E Ozols; R C Atkins; B J Rollin; G H Tesch

2006-01-01

251

Defective STAT signaling by the leptin receptor in diabetic mice.  

PubMed Central

Leptin and its receptor, obese receptor (OB-R), comprise an important signaling system for the regulation of body weight. Splice variants of OB-R mRNA encode proteins that differ in the length of their cytoplasmic domains. We cloned a long isoform of the wild-type leptin receptor that is preferentially expressed in the hypothalamus and show that it can activate signal transducers and activators of transcription (STAT)-3, STAT-5, and STAT-6. A point mutation within the OB-R gene of diabetic (db) mice generates a new splice donor site that dramatically reduces expression of this long isoform in homozygous db/db mice. In contrast, an OB-R protein with a shorter cytoplasmic domain is present in both db/db and wild-type mice. We show that this short isoform is unable to activate the STAT pathway. These data provide further evidence that the mutation in OB-R causes the db/db phenotype and identify three STAT proteins as potential mediators of the anti-obesity effects of leptin. Images Fig. 2 Fig. 3

Ghilardi, N; Ziegler, S; Wiestner, A; Stoffel, R; Heim, M H; Skoda, R C

1996-01-01

252

Apolipoprotein E4 Exaggerates Diabetic Dyslipidemia and Atherosclerosis in Mice Lacking the LDL Receptor  

PubMed Central

OBJECTIVE We investigated the differential roles of apolipoprotein E (apoE) isoforms in modulating diabetic dyslipidemia—a potential cause of the increased cardiovascular disease risk of patients with diabetes. RESEARCH DESIGN AND METHODS Diabetes was induced using streptozotocin (STZ) in human apoE3 (E3) or human apoE4 (E4) mice deficient in the LDL receptor (LDLR?/?). RESULTS Diabetic E3LDLR?/? and E4LDLR?/? mice have indistinguishable levels of plasma glucose and insulin. Despite this, diabetes increased VLDL triglycerides and LDL cholesterol in E4LDLR?/? mice twice as much as in E3LDLR?/? mice. Diabetic E4LDLR?/? mice had similar lipoprotein fractional catabolic rates compared with diabetic E3LDLR?/? mice but had larger hepatic fat stores and increased VLDL secretion. Diabetic E4LDLR?/? mice demonstrated a decreased reliance on lipid as an energy source based on indirect calorimetry. Lower phosphorylated acetyl-CoA carboxylase content and higher gene expression of fatty acid synthase in the liver indicated reduced fatty acid oxidation and increased fatty acid synthesis. E4LDLR?/? primary hepatocytes cultured in high glucose accumulated more intracellular lipid than E3LDLR?/? hepatocytes concomitant with a 60% reduction in fatty acid oxidation. Finally, the exaggerated dyslipidemia in diabetic E4LDLR?/? mice was accompanied by a dramatic increase in atherosclerosis. CONCLUSIONS ApoE4 causes severe dyslipidemia and atherosclerosis independent of its interaction with LDLR in a model of STZ-induced diabetes. ApoE4-expressing livers have reduced fatty acid oxidation, which contributes to the accumulation of tissue and plasma lipids.

Johnson, Lance A.; Arbones-Mainar, Jose M.; Fox, Raymond G.; Pendse, Avani A.; Altenburg, Michael K.; Kim, Hyung-Suk; Maeda, Nobuyo

2011-01-01

253

Impact of experimental type 1 diabetes mellitus on systemic and coagulation vulnerability in mice acutely exposed to diesel exhaust particles.  

PubMed

BACKGROUND: Epidemiological evidence indicates that diabetic patients have increased susceptibility to adverse cardiovascular outcomes related to acute increases in exposures to particulate air pollution. However, mechanisms underlying these effects remain unclear. METHODS: To evaluate the possible mechanisms underlying these actions, we assessed the systemic effects of diesel exhaust particles (DEP) in control mice, and mice with streptozotocin--induced type 1 diabetes. Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4 mg/kg) or saline, and several cardiovascular endpoints were measured 24 h thereafter. RESULTS: DEP caused leucocytosis and a significant increase in plasma C-reactive protein and 8-isoprostane concentrations in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. The arterial PO2 as well as the number of platelets and the thrombotic occlusion time in pial arterioles assessed in vivo were significantly decreased following the i.t. instillation of DEP in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. Both alanine aminotransferase and aspartate transaminase activities, as well as the plasma concentrations of plasminogen activator inhibitor and von Willebrand factor were significantly increased in DEP-exposed diabetic mice compared to diabetic mice exposed to saline or DEP-exposed non-diabetic mice. The in vitro addition of DEP (0.25-1 mug/ml) to untreated mouse blood significantly and dose-dependently induced in vitro platelet aggregation, and these effects were exacerbated in blood of diabetic mice. CONCLUSION: This study has shown that systemic and coagulation events are aggravated by type 1 diabetes in mice, and described the possible mechanisms for these actions that may also be relevant to the exacerbation of cardiovascular morbidity accompanying particulate air pollution in diabetic patients. PMID:23587270

Nemmar, Abderrahim; Subramaniyan, Deepa; Yasin, Javed; Ali, Badreldin H

2013-04-15

254

Impact of experimental type 1 diabetes mellitus on systemic and coagulation vulnerability in mice acutely exposed to diesel exhaust particles  

PubMed Central

Background Epidemiological evidence indicates that diabetic patients have increased susceptibility to adverse cardiovascular outcomes related to acute increases in exposures to particulate air pollution. However, mechanisms underlying these effects remain unclear. Methods To evaluate the possible mechanisms underlying these actions, we assessed the systemic effects of diesel exhaust particles (DEP) in control mice, and mice with streptozotocin–induced type 1 diabetes. Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4 mg/kg) or saline, and several cardiovascular endpoints were measured 24 h thereafter. Results DEP caused leukocytosis and a significant increase in plasma C-reactive protein and 8-isoprostane concentrations in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. The arterial PO2 as well as the number of platelets and the thrombotic occlusion time in pial arterioles assessed in vivo were significantly decreased following the i.t. instillation of DEP in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. Both alanine aminotransferase and aspartate transaminase activities, as well as the plasma concentrations of plasminogen activator inhibitor and von Willebrand factor were significantly increased in DEP-exposed diabetic mice compared to diabetic mice exposed to saline or DEP-exposed non-diabetic mice. The in vitro addition of DEP (0.25-1 ?g/ml) to untreated mouse blood significantly and dose-dependently induced in vitro platelet aggregation, and these effects were exacerbated in blood of diabetic mice. Conclusion This study has shown that systemic and coagulation events are aggravated by type 1 diabetes in mice, acutely exposed to DEP and has described the possible mechanisms for these actions that may also be relevant to the exacerbation of cardiovascular morbidity accompanying particulate air pollution in diabetic patients.

2013-01-01

255

RAGE deficiency improves postinjury sciatic nerve regeneration in type 1 diabetic mice.  

PubMed

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

2012-11-19

256

Type-1 diabetes exaggerates features of Alzheimer's disease in APP transgenic mice  

PubMed Central

A number of studies suggest an association between Alzheimer's disease (AD) and diabetes: AD patients show impaired insulin function, whereas cognitive deficits and increased risk of developing AD occur in diabetic patients. The reasons for the increased risk are not known. Recent studies of disturbances in the insulin-signaling pathway have revealed new perspectives on the links between AD and Type 1 diabetes with a particular focus on glycogen synthase-kinase-3 (GSK3). We have therefore characterized a mouse model of combined insulin-deficient diabetes and AD and find that diabetes exaggerated defects in the brain of APP transgenic mice. Mice with combined APP overexpression and diabetes showed a decreased insulin receptor activity and an increased GSK3? activity. Concomitantly, tau phosphorylation and number of A? plaques, the two pathologic hallmarks of AD, were increased in the brain of diabetic-APP transgenic mice. Our results indicate that the pathologic features of AD are exaggerated in the brain of APP transgenic mice that have concurrent insulin-deficient diabetes, and underscore a possible mechanism of brain dysfunction common to AD and diabetes.

Jolivalt, Corinne G.; Hurford, Rosemarie; Lee, Corinne A.; Dumaop, Wilmar; Rockenstein, Edward; Masliah, Eliezer

2009-01-01

257

Deletion of Aldose Reductase from Mice Inhibits Diabetes-Induced Retinal Capillary Degeneration and Superoxide Generation  

PubMed Central

Purpose Pharmacologic inhibition of aldose reductase (AR) previously has been studied with respect to diabetic retinopathy with mixed results. Since drugs can have off-target effects, we studied the effects of AR deletion on the development and molecular abnormalities that contribute to diabetic retinopathy. Since recent data suggests an important role for leukocytes in the development of the retinopathy, we determined also if AR in leukocytes contributes to leukocyte-mediated death of retinal endothelial cells in diabetes. Methods Wild-type (WT; C57BL/6J) and AR deficient (AR?/?) mice were made diabetic with streptozotocin. Mice were sacrificed at 2 and 10 months of diabetes to evaluate retinal vascular histopathology, to quantify retinal superoxide production and biochemical and physiological abnormalities in the retina, and to assess the number of retinal endothelial cells killed by blood leukocytes in a co-culture system. Results Diabetes in WT mice developed the expected degeneration of retinal capillaries, and increased generation of superoxide by the retina. Leukocytes from diabetic WT mice also killed more retinal endothelial cells than did leukocytes from nondiabetic animals (p<0.0001). Deletion of AR largely (P<0.05) inhibited the diabetes-induced degeneration of retinal capillaries, as well as the increase in superoxide production by retina. AR-deficiency significantly inhibited the diabetes-induced increase in expression of inducible nitric oxide synthase (iNOS) in retina, but had no significant effect on expression of intercellular adhesion molecule-1 (ICAM-1), phosphorylated p38 MAPK, or killing of retinal endothelial cells by leukocytes. Conclusions AR contributes to the degeneration of retinal capillaries in diabetic mice. Deletion of the enzyme inhibits the diabetes-induced increase in expression of iNOS and of superoxide production, but does not correct a variety of other pro-inflammatory abnormalities associated with the development of diabetic retinopathy.

Tang, Jie; Du, Yunpeng; Petrash, J. Mark; Sheibani, Nader; Kern, Timothy S.

2013-01-01

258

Protective effect of brain-derived neurotrophic factor on pancreatic islets in obese diabetic mice  

Microsoft Academic Search

We have previously demonstrated that brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and energy expenditure in obese diabetic db\\/db mice. In the present study, the effect of BDNF treatment on pancreatic islets of db\\/db mice was examined, using vehicle-treated pair-fed db\\/db mice as controls. Brain-derived neurotrophic factor (10 mg\\/kg) or vehicle was subcutaneously administered to male db\\/db mice for 4

Mitsugu Yamanaka; Yasushi Itakura; Tadashi Inoue; Atsushi Tsuchida; Tsutomu Nakagawa; Hiroshi Noguchi; Mutsuo Taiji

2006-01-01

259

Optical cryo-imaging of kidney mitochondrial redox state in diabetic mice models  

NASA Astrophysics Data System (ADS)

Oxidative stress (OS), which increases during diabetes, exacerbates the development and progression of diabetes complications including renal vascular and proximal tubule cell dysfunction. The objective of this study was to investigate the changes in the metabolic state of the tissue in diabetic mice kidneys using fluorescence imaging. Mitochondrial metabolic coenzymes NADH (Nicotinamide Adenine Dinucleotide), and FADH-2 (Flavin Adenine Dinucleotide) are autofluorescent and can be monitored without exogenous labels by optical techniques. The ratio of the fluorescence intensity of these fluorophores, (NADH/FAD), called the NADH redox ratio (RR), is a marker of metabolic state of a tissue. We examined mitochondrial redox states of kidneys from diabetic mice, Akita/+ and its control wild type (WT) for a group of 8- and 12-week-old mice. Average intensity and histogram of maximum projected images of FAD, NADH, and NADH RR were calculated for each kidney. Our results indicated a 17% decrease in the mean NADH RR of the kidney from 8-week-old mice compared with WT mice and, a 30% decrease in the mean NADH RR of kidney from12-week-old mice compared with WT mice. These results indicated an increase in OS in diabetic animals and its progression over time. Thus, NADH RR can be used as a hallmark of OS in diabetic kidney allowing temporal identification of oxidative state.

Maleki, S.; Sepehr, R.; Staniszewski, K.; Sheibani, N.; Sorenson, C. M.; Ranji, M.

2012-02-01

260

Humanized mice for the study of type 1 diabetes and beta cell function.  

PubMed

Our understanding of the basic biology of diabetes has been guided by observations made using animal models, particularly rodents. However, humans are not mice, and outcomes predicted by murine studies are not always representative of actual outcomes in the clinic. In particular, investigators studying diabetes have relied heavily on mouse and rat models of autoimmune type 1-like diabetes, and experimental results using these models have not been representative of many of the clinical trials in type 1 diabetes. In this article, we describe the availability of new models of humanized mice for the study of three areas of diabetes. These include the use of humanized mice for the study of (1) human islet stem and progenitor cells, (2) human islet allograft rejection, and (3) human immunity and autoimmunity. These humanized mouse models provide an important preclinical bridge between in vitro studies and rodent models and the translation of discoveries in these model systems to the clinic. PMID:19120266

King, Marie; Pearson, Todd; Rossini, Aldo A; Shultz, Leonard D; Greiner, Dale L

2008-12-01

261

Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging  

Microsoft Academic Search

All juvenile mice of the nonobese diabetic (NOD) strain develop insulitis, but there is considerable variation in their progression to diabetes. Here we used a strategy based on magnetic resonance imaging (MRI) of magnetic nanoparticles to noninvasively visualize local effects of pancreatic-islet inflammation to predict the onset of diabetes in NOD mice. MRI signals acquired during a narrow early time

Wenxian Fu; Gregory Wojtkiewicz; Ralph Weissleder; Christophe Benoist; Diane Mathis

2012-01-01

262

Overexpression of thioredoxin1 in transgenic mice suppresses development of diabetic nephropathy  

Microsoft Academic Search

Background. Oxidative stress has been suggested to play an important role in the pathogenesis of diabetic nephropathy. In the present study, the effects of thioredoxin1 (TRX1) overexpression, a small protein with antioxidant property, on the development of diabetic nephropathy in streptozotocin-induced dia- betic animals were investigated using TRX1 transgenic mice (TRX1-Tg). Methods. Eight-week-old male TRX1-Tg and wild- type mice littermates

Yasuhiro Hamad; Satoshi Miyata; Tomoko Nii-Kono; Riko Kitazawa; Sohei Kitazawa; Satomi Higo; Michiru Fukunaga; Shigemitu Ueyama; Hajime Nakamura; Junji Yodoi; Masafumi Fukagawa; Masato Kasuga

2007-01-01

263

Antidiabetic effect of watermelon ( Citrullus vulgaris Schrad) on Streptozotocin-induced diabetic mice  

Microsoft Academic Search

The anti-diabetic potential of watermelon (Citrullus vulgaris Schrad) was evaluated in vivo. ICR mice were fed experimental diet containing none, 10% watermelon flesh powder (WM-P) or 1% watermelon rind ethanol extract\\u000a (WM-E). At the end of 4 weeks, mice were administrated with streptozotocin (40 mg\\/kg, i.p.) for 5 consecutive days to induce diabetes. Supplementation with WM-E significantly decreased blood glucose

Jiyun Ahn; Wonhee Choi; Suna Kim; Taeyoul Ha

2011-01-01

264

Initiation of autoimmune diabetes in NOD\\/Lt mice is MHC class I-dependent  

Microsoft Academic Search

MHC class II alleles clearly contribute a primary genetic component of susceptibility to autoimmune insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. However, IDDM does not occur in NOD mice made MHC class I-deficient by a functionally inactivated beta2-microglobulin allele (beta2m(null)). In the present study the beta2m(null) mutation was used to examine the relative contributions of MHC class I

D V Serreze; H D Chapman; D S Varnum; I Gerling; E H Leiter; L D Shultz

1997-01-01

265

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

266

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

Microsoft Academic Search

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

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

2011-01-01

267

Genetic Control of T and B Lymphocyte Activation in Nonobese Diabetic Mice1  

Microsoft Academic Search

Type 1 diabetes in nonobese diabetic (NOD) mice is characterized by the infiltration of T and B cells into pancreatic islets. T cells bearing the TCR V3 chain are disproportionately represented in the earliest stages of islet infiltration (insulitis) despite clonal deletion of most V3 immature thymocytes by the mammary tumor virus-3 (Mtv-3) superantigen (SAg). In this report we showed

Priscilla P. L. Chiu; Anthony M. Jevnikar; Jayne S. Danska

2001-01-01

268

Female exhibited severe cognitive impairment in type 2 diabetes mellitus mice  

Microsoft Academic Search

AimsSex-specific medicine has been highlighted as a different approach to the diagnosis and treatment of diseases between men and women. Type 2 diabetes has been reported to be a risk factor for cognitive impairment. Here, we investigated the sex difference in cognitive function associated with diabetes using KKAy mice.

Akiko Sakata; Masaki Mogi; Jun Iwanami; Kana Tsukuda; Li-Juan Min; Fei Jing; Masaru Iwai; Masaharu Ito; Masatsugu Horiuchi

2010-01-01

269

Enhanced susceptibility of mice with streptozotocin-induced diabetes to type II group B streptococcal infection.  

PubMed Central

Since diabetes mellitus predisposes adults to group B streptococcal (GBS) bacteremia, a murine model of streptozotocin-induced diabetes and type II GBS bacteremia was developed to assess certain immune factors which might influence susceptibility to infection. In diabetic mice, the 50% lethal dose for two strains of type II GBS was significantly lower (greater than 1 log10 decrease in CFU per milliliter) than in control animals. This enhanced virulence of GBS for diabetic animals was associated with prolonged bacteremia, persistent sequestration of organisms in the splanchnic reticuloendothelial system, and a shift from splenic to hepatic clearance. Although immunization of control and diabetic animals resulted in high concentrations of type-specific serum antibody, it had no effect on late reticuloendothelial system sequestration in diabetics. In contrast, depletion of complement by treatment of mice with cobra venom factor blocked reticuloendothelial system clearance and resulted in fatal infection in both diabetic and control mice. These results indicate that neither type-specific antibody nor an intact complement system is adequate for effective clearance of type II GBS bacteremia in mice with experimentally induced diabetes. This clearance deficit could be the result of a defect in hepatocyte membrane receptors necessary for removal of this encapsulated microorganism.

Edwards, M S; Fuselier, P A

1983-01-01

270

Enhanced susceptibility of mice with streptozotocin-induced diabetes to type II group B streptococcal infection.  

PubMed

Since diabetes mellitus predisposes adults to group B streptococcal (GBS) bacteremia, a murine model of streptozotocin-induced diabetes and type II GBS bacteremia was developed to assess certain immune factors which might influence susceptibility to infection. In diabetic mice, the 50% lethal dose for two strains of type II GBS was significantly lower (greater than 1 log10 decrease in CFU per milliliter) than in control animals. This enhanced virulence of GBS for diabetic animals was associated with prolonged bacteremia, persistent sequestration of organisms in the splanchnic reticuloendothelial system, and a shift from splenic to hepatic clearance. Although immunization of control and diabetic animals resulted in high concentrations of type-specific serum antibody, it had no effect on late reticuloendothelial system sequestration in diabetics. In contrast, depletion of complement by treatment of mice with cobra venom factor blocked reticuloendothelial system clearance and resulted in fatal infection in both diabetic and control mice. These results indicate that neither type-specific antibody nor an intact complement system is adequate for effective clearance of type II GBS bacteremia in mice with experimentally induced diabetes. This clearance deficit could be the result of a defect in hepatocyte membrane receptors necessary for removal of this encapsulated microorganism. PMID:6339383

Edwards, M S; Fuselier, P A

1983-02-01

271

Polyploidy and chromatin remodeling in hepatocytes from insulin-dependent diabetic and normoglycemic aged mice.  

PubMed

Changes in polyploidization, chromatin supraorganization, and chromatin accessibility were investigated in hepatocytes collected from adult, nonobese diabetic (NOD) mice with increasing hyperglycemia and compared with adult normoglycemic controls and 56-week-old normoglycemic BALB/c mice. Our goal was to determine the changes in ploidy degrees and chromatin characteristics in mouse hepatocytes that are associated with insulin-dependent diabetes and to detect similarities in these aspects with those verified with aging, with greater accuracy than previous studies. Image analysis of Feulgen-stained nuclei revealed changes in ploidy degrees and chromatin supraorganization. Chromatin accessibility was assessed with micrococcal nuclease (MNase) digestion. Increased polyploidy was associated with increasing levels of glycemia, and this trend toward polyploidy was found even under normoglycemic conditions in NOD mice. Although high degrees of ploidy were also detected in aged BALB/c mice, the magnitude of polyploidy was not the same magnitude as that in the diabetic mice. While there was increased homogeneity of chromatin packaging with increasing polyploidy under conditions of severe hyperglycemia (and even under conditions of normoglycemia) in NOD mice, an inverse relationship was observed in aged BALB/c mice. Chromatin accessibility to MNase increased under severe hyperglycemia and advanced age, but it was much higher in the diabetic mice. In conclusion, although similarities in polyploidy were observed between the hepatocytes from increasingly hyperglycemic adult mice and those from normoglycemic aged mice, the relationship between chromatin remodeling and increases in ploidy degrees was not the same between the hepatocytes of these two groups. These findings demonstrate that strict similarities between diabetes and aging are not always true at the cellular level. This discordance is likely due to differences in the metabolic state of mouse hepatocytes during aging and diabetic conditions consequent to specificities in their gene regulatory programs. PMID:22837107

Ghiraldini, Flávia G; Silva, Isabela S; Mello, Maria Luiza S

2012-07-26

272

Reversal of preexisting hyperglycemia in diabetic mice by acute deletion of the Men1 gene  

PubMed Central

A hallmark of diabetes is an absolute or relative reduction in the number of functional ? cells. Therapies that could increase the number of endogenous ? cells under diabetic conditions would be desirable. Prevalent gene targeting mouse models for assessing ?-cell proliferation and diabetes pathogenesis only address whether deletion of a gene prevents the development of diabetes. Models testing whether acute excision of a single gene can ameliorate or reverse preexisting hyperglycemia in established diabetes remain to be explored, which could directly validate the effect of gene excision on treating diabetes. Here, we report that acute and temporally controlled excision of the Men1 gene, which encodes menin, ameliorated preexisting hyperglycemia in streptozotocin-treated mice. Moreover, Men1 excision also improved the preexisting hyperglycemia and glucose intolerance in genetic db/db diabetic mice. Furthermore, acute Men1 excision reversed preexisting glucose intolerance in high-fat diet-fed mice. Men1 excision improved glucose metabolism at least partly through increasing proliferation of endogenous ? cells and islet size. Acute Men1 excision up-regulated a group of proproliferative genes in pancreatic islets. Together, these findings demonstrate that established hyperglycemia can be reversed through repression of a single gene, Men1, in diabetic conditions, and suggest that menin is a vital regulator in pathogenesis of diabetes.

Yang, Yuqing; Gurung, Buddha; Wu, Ting; Wang, Haoren; Stoffers, Doris A.; Hua, Xianxin

2010-01-01

273

Cilostazol improves the response to ischemia in diabetic mice by a mechanism dependent on PPAR?.  

PubMed

Cilostazol is effective for the treatment of peripheral ischemia. This compound has several beneficial effects on platelet aggregation, serum lipids and endothelial cells, and we recently found that it enhances collateral blood flow in the ischemic hind limbs of mice. Peroxisome proliferator-activated receptor (PPAR)?, a receptor for thiazolidinediones, plays a role in angiogenesis. The aim of this work was to investigate the underlying molecular mechanisms and effects of cilostazol in a model of peripheral ischemia in diabetic mice. We induced diabetes in mice by streptozotocin (STZ) administration and studied ischemia-induced angiogenesis in the ischemic hind limbs of cilostazol-treated and untreated control mice. We found that perfusion recovery was significantly improved in treated compared with control diabetic mice. Interestingly, we found that the expression of PPAR? is reduced in ischemic tissues of diabetic mice. Furthermore, we discovered that local inhibition of the activity of this nuclear receptor decreased the angiogenic response to cilostazol treatment. Finally, we noted that this phenomenon is dependent on VEGF and modulated by PPAR?. Cilostazol administration enhances collateral blood flow in the ischemic hind limbs of STZ-induced diabetic mice through a PPAR?-dependent mechanism. PMID:23891623

Biscetti, Federico; Pecorini, Giovanni; Arena, Vincenzo; Stigliano, Egidio; Angelini, Flavia; Ghirlanda, Giovanni; Ferraccioli, Gianfranco; Flex, Andrea

2013-07-23

274

Sex difference in cardiomyocyte function in normal and metallothionein transgenic mice: the effect of diabetes mellitus.  

PubMed

Evidence suggests a sex difference in intrinsic physiological and diabetic myocardial contractile function related to antioxidant properties of female ovarian hormones. This study was designed to examine the effect of cardiac overexpression of antioxidant metallothionein on intrinsic and diabetic cardiomyocyte function. Weight-matched wild-type (FVB) and metallothionein transgenic mice of both sexes were made diabetic with streptozotocin (220 mg/kg). Contractile and intracellular Ca2+ properties were evaluated including peak shortening (PS), time to PS, time to 90% relengthening (TR90), maximal velocity of shortening or relengthening (+/- dL/dt), fura-2 fluorescence intensity change, and Ca2+ decay rate. Akt and transcription factor c-Jun levels were evaluated by Western blot. Myocytes from female FVB mice exhibited lower PS, +/- dL/dt, and fura-2 fluorescence intensity change, prolonged time to PS, TR90, and Ca2+ decay compared with male FVB mice. Interestingly, this sex difference was not present in metallothionein mice. Diabetes depressed PS, +/-dL/dt and caffeine-induced Ca2+ release, as well as prolonged TR90 and Ca2+ decay in male FVB mice, whereas it only reduced PS in female FVB mice. These diabetic dysfunctions were nullified by metallothionein in both sexes. Females displayed elevated Akt phosphorylation and reduced c-Jun phosphorylation. Diabetes dampened Akt phosphorylation in male FVB mice and enhanced c-Jun in both sexes. Diabetes-induced alterations in Akt phosphorylation and c-Jun were abolished by metallothionein. The sex difference in Akt phosphorylation but not c-Jun levels was reversed by metallothionein. These data indicate that antioxidant capacity plays an important role in sex differences in both intrinsic and diabetic cardiomyocyte contractile properties possibly related to phosphorylation of Akt and c-Jun. PMID:16410376

Ceylan-Isik, Asli F; LaCour, Karissa H; Ren, Jun

2006-01-12

275

Protective effects of combined micronutrients on islet beta-cells of streptozotocin-induced diabetic mice.  

PubMed

There is a tendency for the incidence of diabetes in a population to increase with an improvement in living standards. This would imply the involvement of nutritional factors in the development of diabetes, and so nutritional considerations could be a key aspect in the research and development of an effective remedy for diabetes. In this study, combined micronutrients (selenium, vitamin E, vanadium, and chromium) were orally supplemented to streptozotocin-induced diabetic mice. Results showed that combined micronutrients could decrease the high blood glucose levels (p<0.05 or p<0.01) of diabetic mice. The protective effects of combined micronutrients on structures of beta-cells in pancreatic islets of diabetic mice were observed histopathologically and ultrastructurally. In addition, the supplementation of combined micronutrients increased insulin expression by beta-cells in pancreatic islets of diabetic mice at both translational and transcriptional levels. The immune molecular mechanisms involved were preliminarily regarded as downregulation of the expression of pathogenic T-helper 1 lymphocyte (Th1) cytokine tumor necrosis factor-alpha (TNF-alpha) (p<0.01) along with upregulation of the expression of protective T-helper 2 lymphocyte Th2 cytokine interleukin 10 (IL-10) (p<0.01) which ameliorates the Th1/Th2 imbalance in diabetes. In conclusion, supplementation of combined micronutrients to diabetic mice could effectively improve disordered glucose metabolism, protect islet structures, and improve the function of beta-cells in pancreatic islets, which are affected by differential regulation of the expression of Th1/Th2 cytokines involved in the pathogenesis of diabetes. PMID:20108212

Chang, Ying; Zhang, Gui-Zhen; Piao, Song-Lan; Gao, Shen; Zheng, De-Ming; Song, Yang; Tsicopoulos, Anne; Ying, Sun

2009-03-01

276

Systems genetics of susceptibility to obesity-induced diabetes in mice  

PubMed Central

Inbred strains of mice are strikingly different in susceptibility to obesity-driven diabetes. For instance, deficiency in leptin receptor (db/db) leads to hyperphagia and obesity in both C57BL/6 and DBA/2 mice, but only on the DBA/2 background do the mice develop beta-cell loss leading to severe diabetes, while C57BL/6 mice are relatively resistant. To further investigate the genetic factors predisposing to diabetes, we have studied leptin receptor-deficient offspring of an F2 cross between C57BL/6J (db/+) males and DBA/2J females. The results show that the genetics of diabetes susceptibility are enormously complex and a number of quantitative trait loci (QTL) contributing to diabetes-related traits were identified, notably on chromosomes 4, 6, 7, 9, 10, 11, 12, and 19. The Chr. 4 locus is likely due to a disruption of the Zfp69 gene in C57BL/6J mice. To identify candidate genes and to model coexpression networks, we performed global expression array analysis in livers of the F2 mice. Expression QTL (eQTL) were identified and used to prioritize candidate genes at clinical trait QTL. In several cases, clusters of eQTLs colocalized with clinical trait QTLs, suggesting a common genetic basis. We constructed coexpression networks for both 5 and 12 wk old mice and identified several modules significantly associated with clinical traits. One module in 12 wk old mice was associated with several measures of hepatic fat content as well as with other lipid- and diabetes-related traits. These results add to the understanding of the complex genetic interactions contributing to obesity-induced diabetes.

van Nas, Atila; Castellani, Lawrence W.; Zhao, Yi; Zhou, Zhiqiang; Wen, Pingzi; Yu, Suzanne; Qi, Hongxiu; Rosales, Melenie; Schadt, Eric E.; Broman, Karl W.; Peterfy, Miklos; Lusis, Aldons J.

2012-01-01

277

Anti-diabetic effect of trigonelline and nicotinic acid, on KK-A(y) mice.  

PubMed

Trigonelline (TRG) and nicotinic acid (NA), in which the former but not the latter improved the blood glucose level in the oral glucose tolerance test (OGTT) in Goto-Kakizaki (GK) rats were tested for anti-diabetic effects in mellitus models of KK-A(y) obese mice that had type 2 diabetes. Blood glucose level in OGTT carried out on day 22-23 was lowered after feeding in mice fed TRG and NA than that of the control mice not fed these compounds, indicating that both TRG and NA have sufficient activity to improve glucose tolerance in diabetes with obesity. The serum insulin levels at fasting showed significantly lower levels in mice fed TRG, and a lower tendency in mice fed NA, compared with the control mice. The triglyceride (TG) levels in the liver and adipose tissue in mice fed TRG and NA showed lower values or a lower tendency than those of the control mice, indicating that TRG and NA were also effective to improve the changes in lipid levels accompanied with diabetes. Higher values or a higher tendency of the glucokinase (GLK)/glucose-6-phosphatase (G6Pase) ratio in the liver and lower levels of the serum tumor necrosis factor (TNF)-alpha in the TRG- and NA-fed mice, compared to the control mice, suggested that the regulation of GLK and G6Pase, and TNF-alpha production by TRG and NA are closely related in suppressing the progression of diabetes in the KK-A(y) mice. PMID:20423301

Yoshinari, O; Igarashi, K

2010-01-01

278

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.

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

2013-01-01

279

Effects of monosodium glutamate administration in the neonatal period on the diabetic syndrome in KK mice  

Microsoft Academic Search

Summary  Administration of monosodium glutamate (MSG) to KK mice during the neonatal period resulted in a syndrome of obesity, stunting and hypogonadism. In some animals the genetic predisposition to diabetes was unmasked with the development of marked hyperglycaemia and or hyperinsulinaemia. Food intake was not increased compared to controls. The elevated plasma glucose and insulin in fed MSG treated mice fell

D. P. Cameron; T. K.-Y. Poon; G. C. Smith

1976-01-01

280

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.

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

2011-01-01

281

Diabetes-prone NOD mice are resistant to Mycobacterium avium and the infection prevents autoimmune disease.  

PubMed Central

It was recently proposed that the diabetes genes of non-obese diabetic (NOD) mice are linked to the Bcg gene that is associated with resistance to infection by mycobacteria; however, it has not been established whether NOD mice are resistant or susceptible to the infection, although there are previous investigations on response of NOD mice to other intracellular parasites (e.g. Kaye et al., Eur. J. Immunol. 22: 357-364). We have investigated here this question, as well as the consequences of mycobacterial infection on the natural history of murine diabetes. Female NOD mice were intraperitoneally infected with 10(8) viable bacilli of Mycobacterium avium at 2 months of age, i.e. before the mice show diabetes; they were studied up to the sixth month of age (when more than half of untreated female NOD mice show glycosuria). To determine whether NOD mice were susceptible or resistant to M. avium infection, we have compared the kinetics of bacterial growths in liver and spleen of the mice with those determined in M. avium-susceptible (BALB/c) and resistant (C3H) strains of mice. NOD mice were able to control the M. avium infection, following a pattern similar to that observed in infected C3H mice. The mycobacterial infection prevented the expression of diabetes in all of the infected NOD mice and it also decreased the incidence of proteinuria in the treated mice. The infected NOD mice showed a marked enhancement in antibodies against the 65,000 mycobacteria antigen (heat-shock protein (hsp) 65) up to the second month of infection and these elevated titres slowly decreased in the following months; anti-hsp 65 antibodies were not detected in age-matched controls. This is the first demonstration that NOD mice are naturally resistant to mycobacterial infection, and we reinforce evidence on the role of immune response triggered by mycobacteria and its hsp 65 antigen in prevention of diabetes in NOD mice. Images Figure 4 Figure 5

Bras, A; Aguas, A P

1996-01-01

282

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.

2011-08-01

283

Adeno-associated virus vector-mediated IL10 gene delivery prevents type 1 diabetes in NOD mice  

Microsoft Academic Search

The development of spontaneous autoimmune diabetes in nonobese diabetic (NOD) mice provides for their use as a model of human type 1 diabetes. To test the feasibility of muscle-directed gene therapy to prevent type 1 diabetes, we developed recombinant adeno-associated virus (rAAV) vectors containing murine cDNAs for immunomodulatory cytokines IL-4 or IL-10. Skeletal muscle transduction of female NOD mice with

Kevin Goudy; Sihong Song; Clive Wasserfall; Y. Clare Zhang; Matthias Kapturczak; Andrew Muir; Matthew Powers; Marda Scott-Jorgensen; Martha Campbell-Thompson; James M. Crawford; Tamir M. Ellis; Terence R. Flotte; Mark A. Atkinson

2001-01-01

284

Brief communication Dietary supplementation with cacao liquor proanthocyanidins prevents elevation of blood glucose levels in diabetic obese mice  

Microsoft Academic Search

Objective: Effective approaches should be established to prevent the onset of type 2 diabetes mellitus, which has been increasing in developed countries. The present study examined whether dietary supplementation with cacao liquor proanthocyanidins (CLPr) could prevent elevation of blood glucose levels in mice with diabetes mellitus and obesity. Methods: C57BL\\/KsJ-db\\/db (db\\/db) diabetic obese mice and C57BL\\/KsJ-db\\/m (db\\/m) control mice were

Makoto Tomaru; Hirohisa Takano; Naomi Osakabe; Akiko Yasuda; Ken-ichiro Inoue; Rie Yanagisawa; Tsuneto Ohwatari; Hiroshi Uematsu; Meiji Seika Kaisha

2007-01-01

285

Effect of combined hormonal and insulin therapy on the steroid hormone receptors and growth factors signalling in diabetic mice prostate  

PubMed Central

Diabetes causes harmful effects on prostatic morphology and function. However, there still are doubts about the occurrence of various diseases in the prostate, as well as abnormal angiogenesis in relation to diabetes. Thus, the aim of this study was to correlate and quantify the level of the steroid hormone receptors and the angiogenic and antiangiogenic factors in non-obese diabetic mice (Nod) after combined hormonal and insulin therapy. Sixty mice were divided into six groups after 20 days of diabetes: the control group received 0.9% NaCl, as did the diabetic group. The diabetic-insulin group received insulin, the diabetic-testosterone group received testosterone cypionate, the diabetic-oestrogen group received 17?-oestradiol, and the diabetic-insulin–testosterone–oestrogen group received insulin, testosterone and oestrogen simultaneously. After 20 days, the ventral lobe was processed for immunocytochemical and hormonal analyses. The results showed that the lowest serum testosterone and androgen receptor levels were found in the diabetic group and the highest testosterone and androgen receptor levels in the diabetic-insulin–testosterone–oestrogen group. The serum oestrogen level and its receptor showed changes opposite to those of testosterone and its receptor. The endostatin reactivity was mainly decreased in diabetic mice. The greatest IGFR-1 and VEGF reactivities occurred in diabetic mice. Thus, diabetes led to the prostatic hormonal imbalance, affecting molecular dynamics and angiogenesis in this organ. Combined insulin and steroid hormone therapy partially restored the hormonal and angiogenic imbalance caused by diabetes.

Favaro, Wagner J; Cagnon, Valeria H A

2010-01-01

286

Reversal of Type 2 Diabetes in Mice by Products of Malaria Parasites  

Microsoft Academic Search

We have previously shown that infection with Plasmodium yoelii malaria or injection of extracts from malaria-parasitized red cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in mice made moderately diabetic with streptozotocin. Inositol phosphoglycans (IPGs) are released outside cells by hydrolysis of membrane-bound glycosylphosphatidylinositols (GPIs), and act as second messengers mediating insulin action. The C57BL\\/Ks-db\\/db and C57BL\\/6J-ob\\/ob mice

K. M. Elased; K. A. Gumaa; J. B. de Souza; H. Rahmoune; J. H. L. Playfair; T. W. Rademacher

2001-01-01

287

Validated germline-competent embryonic stem cell lines from nonobese diabetic mice.  

PubMed

Nonobese diabetic (NOD) mice provide an excellent model of type 1 diabetes. The genetic contribution to this disease is complex, with more than 20 loci implicated in diabetes onset. One of the challenges for researchers using the NOD mouse model (and, indeed, other models of spontaneous autoimmune disease) has been the high density of sequence variation within candidate chromosomal segments. Furthermore, the scope for analyzing many putative disease loci via gene targeting has been hampered by the lack of NOD embryonic stem (ES) cells. We describe here the derivation of NOD ES cell lines capable of generating chimeric mice after stable genetic modification. These NOD ES cell lines also show efficient germline transmission, with offspring developing diabetes. The availability of these cells will not only enable the dissection of closely linked loci and the role they have in the onset of type 1 diabetes but also facilitate the generation of new transgenics. PMID:19491843

Nichols, Jennifer; Jones, Kenneth; Phillips, Jenny M; Newland, Stephen A; Roode, Mila; Mansfield, William; Smith, Austin; Cooke, Anne

2009-06-02

288

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...

289

Semicarbazide-sensitive amine oxidase in transgenic mice with diabetes  

Microsoft Academic Search

Semicarbazide-sensitive amine oxidase (SSAO) activity in plasma is increased in diabetes, and in particular, in diabetic patients with vascular complications. It has been speculated that SSAO is involved in the development of such complications due to the production of cytotoxic compounds. In this work, we have induced diabetes in a previously described mouse-model, overexpressing SSAO in smooth muscle cells. SSAO

C. Gokturk; J. Nordquist; H. Sugimoto; K. Forsberg-Nilsson; J. Nilsson; L. Oreland

2004-01-01

290

Suppression of streptozotocin-induced type-1 diabetes in mice by radon inhalation.  

PubMed

We examined the protective effect of radon inhalation on streptozotocin (STZ)-induced type-1 diabetes in mice. Mice inhaled radon at concentrations of 1000, 2500, and 5500 Bq/m3 for 24 hours before STZ administration. STZ administration induced characteristics of type-1 diabetes such as hyperglycemia and hypoinsulinemia; however, radon inhalation at doses of 1000 and 5500 Bq/m3 significantly suppressed the elevation of blood glucose in diabetic mice. Serum insulin was significantly higher in mice pre-treated with radon at a dose of 1000 Bq/m3 than in mice treated with a sham. In addition, superoxide dismutase activities and total glutathione contents were significantly higher and lipid peroxide was significantly lower in mice pre-treated with radon at doses of 1000 and 5500 Bq/m3 than in mice treated with a sham. These results were consistent with the result that radon inhalation at 1000 and 5500 Bq/m3 suppressed hyperglycemia. These findings suggested that radon inhalation suppressed STZ-induced type-1 diabetes through the enhancement of antioxidative functions in the pancreas. PMID:23173687

Nishiyama, Y; Kataoka, T; Teraoka, J; Sakoda, A; Tanaka, H; Ishimori, Y; Mitsunobu, F; Taguchi, T; Yamaoka, K

2012-11-22

291

Anti-CD3 treatment cures PDL1-/-.NOD mice of diabetes but precipitates fatal myocarditis  

PubMed Central

Anti-CD3 mAb is an effective therapy that can reverse diabetes in NOD mice and has therapeutic potential in patients with type 1 diabetes (T1D). We administered anti-CD3 to PDL1?/?.NOD mice in order to determine whether this treatment would reverse the development of diabetes in these mice. Mice injected with anti-CD3 neonatally were protected from T1D. However, all of these anti-CD3 treated PDL1?/?.NOD mice developed a wasting disease between 12–20 weeks of age with sudden deterioration and weight loss, leading to death within 3–5 days of development of illness. Histology revealed severe inflammation in the heart and skeletal muscles. These results suggest that deficiency of PDL1 in NOD background has the potential to lead to immune-mediated tissue damage in organs other than the pancreas, but this cannot be appreciated in PDL1?/?.NOD mice as the mice develop T1D at an early age and die from diabetes prior to manifesting other autoimmune diseases.

Mfarrej, Bechara; Keir, Mary; Dada, Shirine; Trikudanathan, Subbulaxmi; Sayegh, Mohamed; Sharpe, Arlene H.; Guleria, Indira

2013-01-01

292

Cardiac-specific overexpression of CYP2J2 attenuates diabetic cardiomyopathy in male streptozotocin-induced diabetic mice.  

PubMed

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; Wang, Dao Wen

2013-05-21

293

Dietary iron restriction inhibits progression of diabetic nephropathy in db/db mice.  

PubMed

Excess iron causes oxidative stress through hydroxyl-radical production via Fenton/Haber-Weiss reactions. Recently, body iron reduction has been found to ameliorate diabetes. In the present study, we examined the protective effect of dietary iron restriction against diabetic nephropathy in the db/db mouse model of diabetic nephropathy using db/m mice as controls. The db/db mice were divided into two groups and fed a normal diet (ND) or a low-iron diet (LID). Increasing urinary albumin excretion was observed in the ND db/db mice, but this was suppressed in db/db mice with LID. Histologically, the db/db mice in the ND group had increased glomerular volume and mesangial area compared with the LID group. Augmented deposition of extracellular matrixes was decreased in db/db mice with LID. In terms of oxidative stress, increased superoxide production observed in the kidneys of the ND db/db mice was diminished in the LID group. NADPH oxidase activity and renal expression of NADPH oxidase components p22(phox) and NADPH oxidase 4 (NOX4) were augmented in the ND group, and this was abolished by LID. There were no differences in expression of renal iron importers, transferrin receptor, or divalent metal transporter-1 between db/m mice and db/db mice. The level of ferroportin, an iron exporter, increased in the kidneys of the db/db mice. Urinary iron excretion was significantly higher in ND db/db mice and was reduced in the LID group. These findings suggest that dietary iron restriction exerts a preventive effect on the progression of diabetic nephropathy partly due to the reduction of oxidative stress. PMID:23389454

Ikeda, Yasumasa; Enomoto, Hideaki; Tajima, Soichiro; Izawa-Ishizawa, Yuki; Kihira, Yoshitaka; Ishizawa, Keisuke; Tomita, Shuhei; Tsuchiya, Koichiro; Tamaki, Toshiaki

2013-02-06

294

Nerve Growth Factor Gene Therapy Using Adeno-Associated Viral Vectors Prevents Cardiomyopathy in Type 1 Diabetic Mice  

PubMed Central

Diabetes is a cause of cardiac dysfunction, reduced myocardial perfusion, and ultimately heart failure. Nerve growth factor (NGF) exerts protective effects on the cardiovascular system. This study investigated whether NGF gene transfer can prevent diabetic cardiomyopathy in mice. We worked with mice with streptozotocin-induced type 1 diabetes and with nondiabetic control mice. After having established that diabetes reduces cardiac NGF mRNA expression, we tested NGF gene therapies with adeno-associated viral vectors (AAVs) for the capacity to protect the diabetic mouse heart. To this aim, after 2 weeks of diabetes, cardiac expression of human NGF or ?-Gal (control) genes was induced by either intramyocardial injection of AAV serotype 2 (AAV2) or systemic delivery of AAV serotype 9 (AAV9). Nondiabetic mice were given AAV2–?-Gal or AAV9–?-Gal. We found that the diabetic mice receiving NGF gene transfer via either AAV2 or AAV9 were spared the progressive deterioration of cardiac function and left ventricular chamber dilatation observed in ?-Gal–injected diabetic mice. Moreover, they were additionally protected from myocardial microvascular rarefaction, hypoperfusion, increased deposition of interstitial fibrosis, and increased apoptosis of endothelial cells and cardiomyocytes, which afflicted the ?-Gal–injected diabetic control mice. Our data suggest therapeutic potential of NGF for the prevention of cardiomyopathy in diabetic subjects.

Meloni, Marco; Descamps, Betty; Caporali, Andrea; Zentilin, Lorena; Floris, Ilaria; Giacca, Mauro; Emanueli, Costanza

2012-01-01

295

Nerve growth factor gene therapy using adeno-associated viral vectors prevents cardiomyopathy in type 1 diabetic mice.  

PubMed

Diabetes is a cause of cardiac dysfunction, reduced myocardial perfusion, and ultimately heart failure. Nerve growth factor (NGF) exerts protective effects on the cardiovascular system. This study investigated whether NGF gene transfer can prevent diabetic cardiomyopathy in mice. We worked with mice with streptozotocin-induced type 1 diabetes and with nondiabetic control mice. After having established that diabetes reduces cardiac NGF mRNA expression, we tested NGF gene therapies with adeno-associated viral vectors (AAVs) for the capacity to protect the diabetic mouse heart. To this aim, after 2 weeks of diabetes, cardiac expression of human NGF or ?-Gal (control) genes was induced by either intramyocardial injection of AAV serotype 2 (AAV2) or systemic delivery of AAV serotype 9 (AAV9). Nondiabetic mice were given AAV2-?-Gal or AAV9-?-Gal. We found that the diabetic mice receiving NGF gene transfer via either AAV2 or AAV9 were spared the progressive deterioration of cardiac function and left ventricular chamber dilatation observed in ?-Gal-injected diabetic mice. Moreover, they were additionally protected from myocardial microvascular rarefaction, hypoperfusion, increased deposition of interstitial fibrosis, and increased apoptosis of endothelial cells and cardiomyocytes, which afflicted the ?-Gal-injected diabetic control mice. Our data suggest therapeutic potential of NGF for the prevention of cardiomyopathy in diabetic subjects. PMID:22187379

Meloni, Marco; Descamps, Betty; Caporali, Andrea; Zentilin, Lorena; Floris, Ilaria; Giacca, Mauro; Emanueli, Costanza

2012-01-01

296

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

PubMed

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 plasma insulin levels were investigated. In four doses of extracts from the spikes of P. vulgaris, extract at dose of 100 mg/kg significantly suppressed the rise in blood glucose after 30 min in the acute glucose tolerance test. Furthermore, this dose was applied in the fellow experiments. A significant decrease in blood glucose levels was observed after treatment of PVE. A combination of PVE and glibenclamide produced a greater effect in blood glucose level than using glibenclamide or PVE alone. PVE enhanced and prolonged the antihyperglycemic effects of exogenous insulin on STZ diabetic mice. Plasma insulin levels were increased with glibenclamide treatment in STZ diabetic mice, whereas such effect was not observed with PVE. These results indicated that P. vulgaris enhances the antihyperglycemic effects of exogenous insulin without stimulating insulin secretion, indicating that insulin sensitivity is increased in STZ diabetic mice. PMID:17392144

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

2007-01-01

297

Exendin-4 improves resistance to Listeria monocytogenes infection in diabetic db/db mice  

PubMed Central

The incidence of diabetes mellitus is increasing among companion animals. This disease has similar characteristics in both humans and animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In the present study, homozygous diabetic (db/db) mice were infected with Listeria (L.) monocytogenes and then treated with the anti-diabetic drug exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b+ macrophage populations with higher lipid content and lower phagocytic activity were observed. Exendin-4 lowered high lipid levels and enhanced phagocytosis in macrophages from db/db mice infected with L. monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved ex vivo bacteria clearance by macrophages in the animals. Liver histology examined during L. monocytogenes infection indicated that abscess formation was much milder in exendin-4-treated db/db mice than in the control animals. Moreover, mechanistic studies demonstrated that expression of ATP binding cassette transporter 1, a sterol transporter, was higher in macrophages isolated from the exendin-4-treated db/db mice. Overall, our results suggest that exendin-4 decreases the risk of infection in diabetic animals by modifying the interaction between intracellular lipids and phagocytic macrophages.

Liu, Hsien Yueh; Chung, Chih-Yao; Yang, Wen-Chin; Liang, Chih-Lung; Wang, Chi-Young; Chang, Chih-Yu

2012-01-01

298

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.

Kim, Hye Kyung

2012-01-01

299

Saturated fatty acids activate ERK signaling to downregulate hepatic sortilin 1 in obese and diabetic mice.  

PubMed

Hepatic VLDL overproduction is a characteristic feature of diabetes and an important contributor to diabetic dyslipidemia. Hepatic sortilin 1 (Sort1), a cellular trafficking receptor, is a novel regulator of plasma lipid metabolism and reduces plasma cholesterol and triglycerides by inhibiting hepatic apolipoprotein B production. Elevated circulating free fatty acids play key roles in hepatic VLDL overproduction and the development of dyslipidemia. This study investigated the regulation of hepatic Sort1 in obesity and diabetes and the potential implications in diabetic dyslipidemia. Results showed that hepatic Sort1 protein was markedly decreased in mouse models of type I and type II diabetes and in human individuals with obesity and liver steatosis, whereas increasing hepatic Sort1 expression reduced plasma cholesterol and triglycerides in mice. Mechanistic studies showed that the saturated fatty acid palmitate activated extracellular signal-regulated kinase (ERK) and inhibited Sort1 protein by mechanisms involving Sort1 protein ubiquitination and degradation. Consistently, hepatic ERK signaling was activated in diabetic mice, whereas blocking ERK signaling by an ERK inhibitor increased hepatic Sort1 protein in mice. These results suggest that increased saturated fatty acids downregulate liver Sort1 protein, which may contribute to the development of dyslipidemia in obesity and diabetes. PMID:23904453

Bi, Lipeng; Chiang, John Y L; Ding, Wen-Xing; Dunn, Winston; Roberts, Benjamin; Li, Tiangang

2013-07-31

300

BTLA targeting modulates lymphocyte phenotype, function, and numbers and attenuates disease in nonobese diabetic mice.  

PubMed

The novel coinhibitory receptor BTLA may have a regulatory role in maintaining peripheral tolerance; however, its role in autoimmune diabetes is unknown. In this study, we show that anti-BTLA mAb 6F7 selectively depleted pathogenic B and CD4+ T(H) cells; enhanced the proportion of cells with the forkhead box p3+ PD-1+CD4+ regulatory T phenotype; and increased the production of potentially protective (IL-10) and detrimental (IL-2, IFN-gamma) cytokines in NOD mice. As interactions between BTLA and PD-1 coinhibitory pathways have been described in the cardiac allograft model, we also investigated if these pathways may have significant interaction in autoimmune diabetes. Anti-BTLA inhibited anti-PD-1-potentiated total IL-12 (p40+p70) production, suggesting the possibility that anti-BTLA may have a greater effect in the setting of anti-PD-1-triggered diabetes. To test this, NOD mice at 4 and 10 weeks of age were treated with anti-BTLA mAb, anti-PD-1 mAb, both mAb, or isotype control and were monitored for diabetes development. Although anti-BTLA mAb delayed diabetes onset significantly in 10- but not 4-week-old NOD mice, anti-BTLA mAb attenuated anti-PD-1-induced diabetes in both age groups. Hence, strategies targeting BTLA+ lymphocytes or therapies enhancing the BTLA-negative cosignal may prove valuable in treating autoimmune diabetes. PMID:19383625

Truong, Wayne; Hancock, Wayne W; Plester, Jennifer C; Merani, Shaheed; Rayner, David C; Thangavelu, Govindarajan; Murphy, Kenneth M; Anderson, Colin C; Shapiro, A M James

2009-04-21

301

Transgenic mice overexpressing insulin-like growth factor-II in ? cells develop type 2 diabetes  

PubMed Central

During embryonic development, insulin-like growth factor-II (IGF-II) participates in the regulation of islet growth and differentiation. We generated transgenic mice (C57BL6/SJL) expressing IGF-II in ? cells under control of the rat Insulin I promoter in order to study the role of islet hyperplasia and hyperinsulinemia in the development of type 2 diabetes. In contrast to islets from control mice, islets from transgenic mice displayed high levels of IGF-II mRNA and protein. Pancreases from transgenic mice showed an increase in ?-cell mass (about 3-fold) and in insulin mRNA levels. However, the organization of cells within transgenic islets was disrupted, with glucagon-producing cells randomly distributed throughout the core. We also observed enhanced glucose-stimulated insulin secretion and glucose utilization in islets from transgenic mice. These mice displayed hyperinsulinemia, mild hyperglycemia, and altered glucose and insulin tolerance tests, and about 30% of these animals developed overt diabetes when fed a high-fat diet. Furthermore, transgenic mice obtained from the N1 backcross to C57KsJ mice showed high islet hyperplasia and insulin resistance, but they also developed fatty liver and obesity. These results indicate that local overexpression of IGF-II in islets might lead to type 2 diabetes and that islet hyperplasia and hypersecretion of insulin might occur early in the pathogenesis of this disease.

Devedjian, Jean-Christophe; George, Monica; Casellas, Alba; Pujol, Anna; Visa, Joana; Pelegrin, Mireia; Gros, Laurent; Bosch, Fatima

2000-01-01

302

Maintenance of islet morphology is beneficial for transplantation outcome in diabetic mice.  

PubMed

We have previously shown that co-transplantation of islets and Mesenchymal Stem Cells (MSCs) improves islet graft function and revascularisation, which was associated with the maintenance of normal islet morphology. The aim of the current study was to determine whether maintaining islet morphology in the absence of additional islet-helper cells would improve transplantation outcome in diabetic mice. Islets were isolated from C57BL/6 mice. Recipient streptozotocin-diabetic C57BL/6 mice were transplanted with a minimal mass of 150 islets as a single pellet or islets that were either manually dispersed or dispersed within a matrigel plug beneath the kidney capsule. Blood glucose concentrations were monitored for one month. Islet graft morphology and vascularisation were analysed by histology. Islets dispersed either alone or within matrigel plugs maintained near normal morphology, in contrast to pelleted islets, where individual islets fused to form large endocrine aggregates. The vascularisation of manually dispersed islets and islets dispersed within matrigel plugs was increased relative to respective control pelleted islet grafts. After one month 1/6 mice transplanted with pelleted islets cured compared to 5/6 mice transplanted with manually dispersed islets. The curative capacity of islets dispersed in matrigel was also better than that of pelleted islets (5/8 islet-matrigel implanted mice vs. 1/7 mice transplanted with pelleted islets cured by one month). Therefore, this study demonstrates that the maintenance of islet morphology is associated with improved graft function and revascularisation in diabetic mice. PMID:23451276

Rackham, Chloe L; Jones, Peter M; King, Aileen J F

2013-02-25

303

Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice  

PubMed Central

Vertebrates typically harbor a rich gastrointestinal microbiota, which has coevolved with the host over millennia and is essential for several host physiological functions, in particular maturation of the immune system. Recent studies have highlighted the importance of a single bacterial species, segmented filamentous bacteria (SFB), in inducing a robust T-helper cell type 17 (Th17) population in the small-intestinal lamina propria (SI-LP) of the mouse gut. Consequently, SFB can promote IL-17–dependent immune and autoimmune responses, gut-associated as well as systemic, including inflammatory arthritis and experimental autoimmune encephalomyelitis. Here, we exploit the incomplete penetrance of SFB colonization of NOD mice in our animal facility to explore its impact on the incidence and course of type 1 diabetes in this prototypical, spontaneous model. There was a strong cosegregation of SFB positivity and diabetes protection in females, but not in males, which remained relatively disease-free regardless of the SFB status. In contrast, insulitis did not depend on SFB colonization. SFB-positive, but not SFB-negative, females had a substantial population of Th17 cells in the SI-LP, which was the only significant, repeatable difference in the examined T-cell compartments of the gut, pancreas, or systemic lymphoid tissues. Th17-signature transcripts dominated the very limited SFB-induced molecular changes detected in SI-LP CD4+ T cells. Thus, a single bacterium, and the gut immune system alterations associated with it, can either promote or protect from autoimmunity in predisposed mouse models, probably reflecting their variable dependence on different Th subsets.

Kriegel, Martin A.; Sefik, Esen; Hill, Jonathan A.; Wu, Hsin-Jung; Benoist, Christophe; Mathis, Diane

2011-01-01

304

The relationship between hyperglycaemia and renal immune complex deposition in mice with inherited diabetes.  

PubMed Central

Kidney lesions were studied by light microscopy and immunofluorescence in diabetic (db/db) and obese (ob/ob) mutant mice. The db/db mutation was studied both on the C57Bl/KsJ genetic background (where it produces severe hyperglycaemia) and on the C57Bl/6J background (where hyperglycaemia is only mild). In all cases, more IgG, IgM and C3 were deposited in the renal glomeruli of mutant mice than in the glomeruli of normal (+/?) mice of equivalent age. First signs of immunoglobulin deposition occurred at a slightly younger age than first signs of C3 deposition or histological change (mainly mesangial thickening). Insulin deposits were occasionally seen in the glomeruli of older mutant mice and immunoglobulin eluted from diabetic mouse kidneys had anti-insulin activity. Increased anti-DNA activity was present in the serum of older mutants. In those mutants with severe hyperglycaemia, the macula densa and distal convoluted tubules also contained immunoglobulin deposits, probably derived from the glomerular mesangium. Urine from diabetic mice contained high molecular weight material reacting with antisera to Fab or kappa but not the Fc portion of immunoglobulin. We conclude that diabetic mice have immune complexes in the kidney containing antibodies against insulin and possibly other antigens. We find no evidence that hyperglycaemia itself is the direct cause of glomerular immune complex deposition, although there may be a link between hyperglycaemia and tubular dysfunction. Images Fig. 3 Fig. 5 Fig. 6

Meade, C J; Brandon, D R; Smith, W; Simmonds, R G; Harris, S; Sowter, C

1981-01-01

305

Neurobehavioral deficits in db\\/db diabetic mice  

Microsoft Academic Search

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.

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

2010-01-01

306

Interaction of insulin with prokinetic drugs in STZ-induced diabetic mice  

PubMed Central

AIM: To study the possible interactions of metoclopramide, domperidone and erythromycin in streptozotocin-induced diabetic mice treated with insulin by various parameters. METHODS: Effects of the individual as well as combined drugs were studied in diabetic mice via estimation of the blood glucose and serum insulin levels, small intestinal transit (SIT), gastric emptying (GE), xylose absorption and glucose tolerance tests. Groups were given insulin 2 IU/kg s.c., metoclopramide 20 mg/kg p.o., domperidone 20 mg/kg p.o. and erythromycin 6 mg/kg p.o. individually and in combination. There were also normal and diabetic control groups. The first set of experiments was carried out to investigate the subchronic effect on blood glucose and serum insulin levels in diabetic mice of one week of daily dose administration of the tested drugs individually as well as the combination of insulin with each prokinetic drug. The other five sets of experiments were carried out to investigate the acute effect of a single dose of each drug individually and in combination on blood glucose and serum insulin levels, SIT, GE, oral xylose absorption and glucose tolerance tests. RESULTS: The study included the prokinetic drugs metoclopramide (20 mg/kg), domperidone (20 mg/kg) and erythromycin (6 mg/kg), as well as insulin (2 IU/kg), which was individually effective in decreasing SIT, enhancing GE and increasing xylose absorption significantly in diabetic mice. Erythromycin tended to decrease blood glucose level and increase serum insulin level after 1 wk of daily administration in diabetic mice. Erythromycin potentiated the effect of insulin on blood glucose level and serum insulin level whereas other prokinetic agents failed to do so after repeated dose administration in diabetic mice. Metoclopramide or erythromycin in combination with insulin significantly decreased SIT, in diabetic mice, to lower levels than with insulin alone. Administration of prokinetic drugs along with insulin antagonized the action of insulin on xylose absorption. These combinations also increased the rate of glucose absorption from the gut. CONCLUSION: The present study suggests that prokinetic drugs could potentially improve glycemic control in diabetic gastroparesis by allowing a more predictable absorption of nutrients, matched to the action of exogenous insulin. The use of prokinetics, such as erythromycin, may be interesting in the clinic in decreasing the need for insulin in diabetic patients. The dose of insulin may be safely decreased with erythromycin in chronic treatments.

Shalaby, Mohamed A Fouad; Latif, Hekma A Abd El; Sayed, Mostafa E El

2013-01-01

307

[Histochemical and ultrastructural observations of limb muscle in spontaneous diabetic mice].  

PubMed

Spontaneous non-obese diabetic (NOD) mice were used to study the morphological change of muscle fibers in diabetes mellitus. The gastrocnemius and soleus muscles were removed from the NOD mice suffering from diabetes mellitus for 1, 3, 6 or 9 weeks. Muscle fibers were observed electronmicroscopically and histochemically, by staining with Sudan black B. Single fiber atrophy was noted in white fibers at an early stage of the illness. At the age of 6 and 9 weeks, white fibers showed extensive damage, characterized by the atrophy and wide separation of myofibrils, irregularity and thinness of myofilaments and massive glycogen deposition. The damage in the myofibril itself, however, was less pronounced in red and intermediate fibers, and those fibers had more abnormal mitochondria and a decreased affinity for sudan pigment. Morphological changes were varied in the three types of fibers. It is concluded that diabetes mellitus had different effects on each three types of muscle fibers neurogenically and metabolically. PMID:1706403

Watanabe, K

1990-12-01

308

Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice.  

PubMed

Diabetes is associated with increased prevalence, severity, and progression of periodontal disease. To test the hypothesis that activation of RAGE (Receptor for Advanced Glycation End products) contributes to the pathogenesis of diabetes-associated periodontitis, we treated diabetic mice, infected with the human periodontal pathogen Porphyromonas gingivalis, with soluble RAGE (sRAGE). sRAGE is the extracellular domain of the receptor, which binds ligand and blocks interaction with, and activation of, cell-surface RAGE. Blockade of RAGE diminished alveolar bone loss in a dose-dependent manner. Moreover, we noted decreased generation of the proinflammatory cytokines TNF-alpha and IL-6 in gingival tissue, as well as decreased levels of matrix metalloproteinases. Gingival AGEs were also reduced in mice treated with sRAGE, paralleling the observed suppression in alveolar bone loss. These findings link RAGE and exaggerated inflammatory responses to the pathogenesis of destructive periodontal disease in diabetes. PMID:10772656

Lalla, E; Lamster, I B; Feit, M; Huang, L; Spessot, A; Qu, W; Kislinger, T; Lu, Y; Stern, D M; Schmidt, A M

2000-04-01

309

Daidzein inhibits carbohydrate digestive enzymes in vitro and alleviates postprandial hyperglycemia in diabetic mice.  

PubMed

This study was designed to investigate whether daidzein inhibits ?-glucosidase and ?-amylase activities and alleviates postprandial hyperglycemia in streptozotocin-induced diabetic mice. Daidzein showed prominent inhibitory effects against ?-glucosidase and ?-amylase. The IC50 values of daidzein against ?-glucosidase and ?-amylase were 0.048 and 0.301 mmol, respectively, which showed that daidzein was more effective than acarbose. The increase in postprandial blood glucose levels was more significantly suppressed in the daidzein-administered group than in the water group of both streptozotocin-induced diabetic and normal mice. Moreover, the area under the curve was significantly lowered following daidzein administration (2043 versus 2475 mmol min l) in the streptozotocin-induced diabetic mice. These results indicated that daidzein may be a potent ?-glucosidase inhibitor and suppress the postprandial hyperglycemia caused by starch. PMID:23669248

Park, Mi-Hwa; Ju, Jae-Won; Park, Min Jung; Han, Ji Sook

2013-05-10

310

Effects of angiotensin II type 1 receptor blocker on bones in mice with type 1 diabetes induced by streptozotocin.  

PubMed

INTRODUCTION: This study was performed to address the pathological roles of the skeletal renin-angiotensin system (RAS) in type 1 diabetes-induced osteoporosis and the effects of the angiotensin II type 1 receptor blocker losartan on bones in diabetic mice. MATERIALS AND METHODS: Bone histomorphology was detected by H&E staining, Safranin O staining and X-ray radiography. Micro-CT was performed for the analysis of bone parameters. Gene and protein expression were determined by RT-PCR and immunoblotting. RESULTS: Type 1 diabetic mice displayed osteopenia phenotype, and losartan treatment had no osteoprotective effects on diabetic mice as shown by the reduction of bone mineral density and microarchitectural parameters at the proximal metaphysis of the tibia. The mRNA expression of AGT, renin receptor and ACE, and protein expression of renin and AT1R were markedly up-regulated in the bones of vehicle-treated diabetic mice compared to those of non-diabetic mice. The treatment with losartan further significantly increased the expression of AGT, renin, angiotensin II and AT1R, and reduced the expression of AT2R receptor as compared to those of diabetic mice. CONCLUSION: Local bone RAS functionally played a role in the development of type 1 diabetic osteoporosis, and losartan had no bone-sparing function in diabetes mice because of enhance skeletal RAS activity. PMID:23283823

Zhang, Yan; Diao, Teng-Yue; Gu, Sa-Sa; Wu, Shu-Yan; Gebru, Yoseph A; Chen, Xi; Wang, Jing-Yu; Ran, Shu; Wong, Man-Sau

2013-01-01

311

Morphofunctional changes underlying intestinal dysmotility in diabetic RIP-I/hIFN? transgenic mice  

PubMed Central

The pathogenetic mechanisms underlying gastrointestinal dysmotility in diabetic patients remain poorly understood, although enteric neuropathy, damage to interstitial cells of Cajal (ICC) and smooth muscle cell injury are believed to play a role. The aim of this study was to investigate the morphological and functional changes underlying intestinal dysmotility in RIP-I/hIFN? transgenic mice treated with multiple very low doses of streptozotocin (20 mg/kg, i.p., 5 days). Compared with vehicle-treated mice, streptozotocin-treated animals developed type 1 diabetes mellitus, with sustained hyperglycaemia for 3.5 months, polyphagia, polydipsia and increased faecal output without changes in faecal water content (metabolic cages). Diabetic mice had a longer intestine, longer ileal villi and wider colonic crypts (conventional microscopy) and displayed faster gastric emptying and intestinal transit. Contractility studies showed selective impaired neurotransmission in the ileum and mid-colon of diabetic mice. Compared with controls, the ileal and colonic myenteric plexus of diabetic mice revealed ultrastructural features of neuronal degeneration and HuD immunohistochemistry on whole-mount preparations showed 15% reduction in neuronal numbers. However, no immunohistochemical changes in apoptosis-related markers were noted. Lower absolute numbers of neuronal nitric oxide synthase- and choline acetyltransferase-immunopositive neurons and enhanced vasoactive intestinal polypeptide and substance P immunopositivity were observed. Ultrastructural and immunohistochemical analyses did not reveal changes in the enteric glial or ICC networks. In conclusion, this model of diabetic enteropathy shows enhanced intestinal transit associated with intestinal remodelling, including neuroplastic changes, and overt myenteric neuropathy. Such abnormalities are likely to reflect neuroadaptive and neuropathological changes occurring in this diabetic model.

Domenech, Anna; Pasquinelli, Gianandrea; De Giorgio, Roberto; Gori, Alessandra; Bosch, Fatima; Pumarola, Marti; Jimenez, Marcel

2011-01-01

312

A Point Mutation in Sec61?1 Leads to Diabetes and Hepatosteatosis in Mice  

PubMed Central

OBJECTIVE Type 2 diabetes is caused by both environmental and genetic factors. To better understand the genetic factors we used forward genetics to discover genes that have not previously been implicated in the development of hyperglycemia or diabetes. RESEARCH DESIGN AND METHODS Offspring of ethylnitrosurea-mutagenized C57BL/6 mice were bred to homozygosity, maintained on high-fat diet, and screened for hyperglycemia. The phenotype in one diabetic family of mice was mapped among hybrid F2s with single nucleotide polymorphic markers, followed by candidate gene sequencing to identify the gene harboring the causative mutation. Subsequent analysis was done on wild-type, heterozygous, and homozygous mutant mice on a pure C57BL/6 background. RESULTS Diabetes mapped to a point mutation in the Sec61a1 gene that encodes a His to Tyr substitution at amino acid 344 (Y344H). Metabolic profiling, histological examination, and electron microscopy revealed that hyperglycemia was a result of insulin insufficiency due to ?-cell apoptosis brought on by endoplasmic reticulum (ER) stress. Transgenic ?-cell–specific expression of Sec61a1 in mutant mice rescued diabetes, ?-cell apoptosis, and ER stress. In vitro experiments showed that Sec61?1 plays a critical role in the ?-cell response to glucose. CONCLUSIONS Here we phenotypically characterize diabetes in mice with a novel point mutation in a basic component of the cell's ER protein translocation machinery, Sec61?1. Translocation by the mutant protein does not appear to be affected. Rather, ER homeostasis is perturbed leading to ?-cell death and diabetes.

Lloyd, David J.; Wheeler, Matthew C.; Gekakis, Nicholas

2010-01-01

313

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.

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

2013-01-01

314

Daily nasal inoculation with the insulin gene ameliorates diabetes in mice  

Microsoft Academic Search

The present study examined the feasibility of liposome-mediated gene transfer via nasal administration, for treating insulin-dependent diabetes mellitus. The rat insulin gene was packed under control of the CMV promoter, complexed with DC-chol\\/DOPE-based liposomes and administered daily via the nasal route in mice made severely diabetic by streptozocin. Sustained expression of the insulin gene was achieved and insulinopenia, ketonuria and

S.-i. Tanaka; T. Yamakawa; M. Kimura; I. Aoki; J. Kamei; K. Okuda; C. Mobbs

2004-01-01

315

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

316

Blockade of Vascular Endothelial Growth Factor Signaling Ameliorates Diabetic Albuminuria in Mice  

Microsoft Academic Search

For investigation of how the vascular endothelial growth factor (VEGF) system participates in the pathogenesis of diabetic kidney disease, type 2 diabetic db\\/db and control db\\/m mice were treated intraperitoneally with vehicle or 2 mg\\/kg of a pan-VEGF receptor tyrosine kinase inhibitor, SU5416, twice a week for 8 wk. Efficacy of SU5416 treatment in the kidney was verified by the

Sun Hee Sung; Fuad N. Ziyadeh; Amy Wang; Petr E. Pyagay; Yashpal S. Kanwar; Sheldon Chen

2006-01-01

317

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

PubMed Central

Type 2 diabetes results from severe insulin resistance coupled with a failure of ?-cells to compensate by secreting sufficient insulin. Multiple genetic loci are involved in the development of diabetes, although the effect of each gene on diabetes susceptibility is thought to be small. MicroRNAs (miRNA) are non-coding 19–22 nucleotide RNA molecules that potentially regulate the expression of thousands of genes. To understand the relationship between miRNA regulation and obesity-induced diabetes, we quantitatively profiled ~220 miRNAs in pancreatic islets, adipose tissue, and liver from diabetes-resistant (B6) and diabetes-susceptible (BTBR) mice. More than half of the miRNAs profiled were expressed in all 3 tissues, with many miRNAs in each tissue showing significant changes in response to genetic obesity. Further, several miRNAs in each tissue were differentially responsive to obesity in B6 versus BTBR mice, suggesting that they may be involved in the pathogenesis of diabetes. In liver, there were ~40 miRNAs that were down-regulated in response to obesity in B6, but not BTBR mice, indicating that genetic differences between the mouse strains play a critical role in miRNA regulation. In order to elucidate the genetic architecture of hepatic miRNA expression, we measured the expression of miRNAs in genetically obese F2 mice. Approximately 10% of the miRNAs measured showed significant linkage (miR-eQTLs), identifying loci that control miRNA abundance. Understanding the influence that obesity and genetics exert on the regulation of miRNA expression will reveal the role miRNAs play in the context of obesity-induced type 2 diabetes.

Zhao, Enpeng; Keller, Mark P.; Rabaglia, Mary E.; Oler, Angie T.; Stapleton, Donnie S.; Schueler, Kathryn L.; Neto, Elias Chaibub; Moon, Jee Young; Wang, Ping; Wang, I-Ming; Lum, Pek; Ivanovska, Irena; Greenawalt, Danielle; Tsang, John; Choi, YounJeong; Kleinhanz, Robert; Shang, Jin; Zhou, Yun-Ping; Howard, Andrew D.; Zhang, Bei B.; Kendziorski, Christina; Thornberry, Nancy A.; Yandell, Brian S.; Schadt, Eric E.; Attie, Alan D.

2010-01-01

318

Monosodium glutamate-induced diabetic mice are susceptible to azoxymethane-induced colon tumorigenesis.  

PubMed

Obese people and diabetic patients are known to be high risk of colorectal cancer (CRC), suggesting need of a new preclinical animal model, by which to extensively study the diverse mechanisms, therapy and prevention. The present study aimed to determine whether experimental obese and diabetic mice produced by monosodium glutamate (MSG) treatment are susceptible to azoxymethane (AOM)-induced colon tumorigenesis using early biomarkers, aberrant crypts foci (ACF) and ?-catenin-accumulated crypts (BCACs), of colorectal carcinogenesis. Male Crj:CD-1 (ICR) newborns were daily given four subcutaneous injections of MSG (2 mg/g body wt) to induce diabetes and obesity. They were then given four intraperitoneal injections of AOM (15 mg/kg body wt) or saline (0.1 ml saline/10 g body wt). Ten weeks after the last injection of AOM, the MSG-AOM mice had a significant increase in the multiplicity of BCAC (13.83 ± 7.44, P < 0.002), but not ACF (78.00 ± 11.20), when compare to the Saline-AOM mice (5.45 ± 1.86 of BCAC and 69.27 ± 8.06 of ACF). Serum biochemical profile of the MSG-treated mice with or without AOM showed hyperinsulinemia, hypercholesteremia and hyperglycemia. The mRNA expression of insulin-like growth factor-1 receptor (IGF-1R, P<0.01) was increased in the MSG-AOM mice, when compared with the mice given AOM alone. IGF-1R was immunohistochemically expressed in the BCAC, but not ACF, in the AOM-treated mice. Our findings suggest that the MSG mice are highly susceptible to AOM-induced colorectal carcinogenesis, suggesting potential utility of our MSG-AOM mice for further investigation of the possible underlying events that affect the positive association between obese/diabetes and CRC. PMID:22223845

Hata, Kazuya; Kubota, Masaya; Shimizu, Masahito; Moriwaki, Hisataka; Kuno, Toshiya; Tanaka, Takuji; Hara, Akira; Hirose, Yoshinobu

2012-01-04

319

Treatment of obesity and diabetes in mice by transplant of gut cells engineered to produce leptin.  

PubMed

Leptin injections evoke weight loss by causing a reduction in food consumption and an increase in energy expenditure. Also, the administration of leptin lowers blood glucose levels in some rodent models of diabetes and in humans with lipodystrophy. We explored the therapeutic potential of delivering leptin to obese, diabetic ob/ob mice and to mice fed on a high-fat diet (HFD), by transplanting gut-derived cells engineered to produce leptin, under the regulation of an inducing agent, mifepristone. These cells expressed and released leptin in a mifepristone dose-dependent and time-dependent manner. The engineered cells were either transplanted into the mice under the kidney capsule or were encapsulated in alginate and injected into the intraperitoneal cavity, while mifepristone was delivered by implanting 14-day release pellets. In ob/ob mice, leptin delivery by this method caused a significant reduction in food intake and profound weight loss, which was controllable by adjusting the dose of mifepristone. These transplants also achieved rapid and persistent amelioration of diabetes. However, mice fed on a HFD were resistant to the leptin therapy. These results indicate that gut cells can be modified to express leptin in an inducible manner and that the transplantation of these cells has a therapeutic effect in leptin-deficient mice, but not in mice fed on a HFD. PMID:18414479

Oosman, Sarah N; Lam, Ada W; Harb, George; Unniappan, Suraj; Lam, Ni T; Webber, Travis; Bruch, Daniel; Zhang, Qiu-Xia; Korbutt, Gregory S; Kieffer, Timothy J

2008-04-15

320

Orally and topically administered Sparassis crispa (Hanabiratake) improved healing of skin wounds in mice with streptozotocin-induced diabetes.  

PubMed

Sparassis crispa (SC) contains significant concentrations of ?-glucan, which can accelerate wound healing, but the dose dependence for oral administration and the effects of topical administration are unknown. In streptozotocin-induced diabetic mice, dietary SC promoted dose-dependent effective wound healing. Similar wound healing activity was observed when purified SC ?-glucan was topically applied to wounds of diabetic mice. PMID:23748764

Yamamoto, Kyosuke; Kimura, Takashi

2013-06-07

321

CTLA-4Ig activates forkhead transcription factors and protects dendritic cells from oxidative stress in nonobese diabetic mice  

Microsoft Academic Search

Prediabetes and diabetes in nonobese diabetic (NOD) mice have been targeted by a variety of immunotherapies, including the use of a soluble form of cytotoxic T lymphocyte antigen 4 (CTLA-4) and interferon (IFN)-gamma. The cytokine, however, fails to activate tolerogenic properties in dendritic cells (DCs) from highly susceptible female mice early in prediabetes. The defect is characterized by impaired induction

Francesca Fallarino; Roberta Bianchi; Ciriana Orabona; Carmine Vacca; Maria L. Belladonna; Maria C. Fioretti; David V. Serreze; Ursula Grohmann; Paolo Puccetti

2004-01-01

322

Thermogenesis in diabetes-obesity syndromes in mutant mice  

Microsoft Academic Search

Summary  The two mouse mutants, obese (ob) and diabetes (db), cause similar diabetes-obesity syndromes that are characterized by a marked increase in apparent metabolic efficiency with regard to utilization of energy. A failure to thermoregulate in a normal fashion would save energy which could then be diverted to other functions and be reflected as increased metabolic efficiency. This study assesses the

D. L. Coleman

1982-01-01

323

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

324

Mechanisms of Mycobacterium avium-induced resistance against insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice: role of Fas and Th1 cells  

PubMed Central

NOD mice spontaneously develop autoimmune diabetes. One of the manipulations that prevent diabetes in NOD mice is infection with mycobacteria or immunization of mice with mycobacteria-containing adjuvant. Infection of NOD mice with Mycobacterium avium, done before the mice show overt diabetes, results in permanent protection of the animals from diabetes and this protective effect is associated with increased numbers of CD4+ T cells and B220+ B cells. Here, we investigate whether the M. avium-induced protection of NOD mice from diabetes was associated with changes in the expression of Fas (CD95) and FasL by immune cells, as well as alterations in cytotoxic activity, interferon-gamma (IFN-?) and IL-4 production and activation of T cells of infected animals. Our data indicate that protection of NOD mice from diabetes is a Th1-type response that is mediated by up-regulation of the Fas–FasL pathway and involves an increase in the cytotoxicity of T cells. These changes are consistent with induction by the infection of regulatory T cells with the ability of triggering deletion or anergy of peripheral self-reactive lymphocytes that cause the autoimmune disease of NOD mice.

Martins, T C; Aguas, A P

1999-01-01

325

The Role of Interstitial Macrophages in Nephropathy of Type 2 Diabetic db/db Mice  

PubMed Central

Diabetic nephropathy is associated with interstitial macrophage infiltrates, but their contribution to disease progression is unclear. We addressed this question by blockade of chemokine receptor (CCR)1 because CCR1 mediates the macrophage recruitment to the renal interstitium. In fact, when CCR1 was blocked with BL5923, a novel orally available CCR1 antagonist, the interstitial recruitment of ex vivo labeled macrophages was markedly decreased in uninephrectomized male db/db mice with advanced diabetic nephropathy. Likewise, BL5923 (60 mg/kg, twice a day) orally administered from months 5 to 6 of life reduced the numbers of interstitial macrophages in uninephrectomized db/db mice. This was associated with reduced numbers of Ki-67 proliferating tubular epithelial and interstitial cells, tubular atrophy, and interstitial fibrosis in uninephrectomized db/db mice. Glomerular pathology and proteinuria were not affected by the CCR1 antagonist. BL5923 reduced renal mRNA expression of Ccl2, Ccr1, Ccr2, Ccr5, transforming growth factor-?1, and collagen I-?1 when compared with untreated uninephrectomized male db/db mice of the same age. Thus, we identified a previously unrecognized role for interstitial macrophages for tubulointerstitial injury, loss of peritubular microvasculature, interstitial inflammation, and fibrosis in type 2 diabetic db/db mice. These data identify oral treatment with the CCR1 antagonist BL5923 as a potential therapy for late-stage diabetic nephropathy.

Ninichuk, Volha; Khandoga, Alexander G.; Segerer, Stephan; Loetscher, Pius; Schlapbach, Achim; Revesz, Laszlo; Feifel, Roland; Khandoga, Andrej; Krombach, Fritz; Nelson, Peter J.; Schlondorff, Detlef; Anders, Hans-Joachim

2007-01-01

326

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

PubMed Central

Impaired oocyte quality has been demonstrated in diabetic mice; however, the potential pathways by which maternal diabetes exerts its effects on the oocyte are poorly understood. Cumulus cells are in direct contact with the oocyte via gap junctions and provide essential nutrients to support oocyte development. In this study, we investigated the effects of maternal diabetes on the mitochondrial status in cumulus cells. We found an increased frequency of fragmented mitochondria, a decreased transmembrane potential and an aggregated distribution of mitochondria in cumulus cells from diabetic mice. Furthermore, while mitochondrial biogenesis in cumulus cells was induced by maternal diabetes, their metabolic function was disrupted as evidenced by lower ATP and citrate levels. Moreover, we present evidence suggesting that the mitochondrial impairments induced by maternal diabetes, at least in part, lead to cumulus cell apoptosis through the release of cytochrome c. Together the deleterious effects on cumulus cells may disrupt trophic and signaling interactions with the oocyte, contributing to oocyte incompetence and thus poor pregnancy outcomes in diabetic females.

Wang, Qiang; Frolova, Antonina I.; Purcell, Scott; Adastra, Katie; Schoeller, Erica; Chi, Maggie M.; Schedl, Tim; Moley, Kelle H.

2010-01-01

327

Alagebrium Reduces Glomerular Fibrogenesis and Inflammation Beyond Preventing RAGE Activation in Diabetic Apolipoprotein E Knockout Mice  

PubMed Central

Advanced glycation end products (AGEs) are important mediators of diabetic nephropathy that act through the receptor for AGEs (RAGE), as well as other mechanisms, to promote renal inflammation and glomerulosclerosis. The relative contribution of RAGE-dependent and RAGE-independent signaling pathways has not been previously studied in vivo. In this study, diabetic RAGE apoE double-knockout (KO) mice with streptozotocin-induced diabetes were treated with the AGE inhibitor, alagebrium (1 mg/kg/day), or the ACE inhibitor, quinapril (30 mg/kg/day), for 20 weeks, and renal parameters were assessed. RAGE deletion attenuated mesangial expansion, glomerular matrix accumulation, and renal oxidative stress associated with 20 weeks of diabetes. By contrast, inflammation and AGE accumulation associated with diabetes was not prevented. However, treatment with alagebrium in diabetic RAGE apoE KO mice reduced renal AGE levels and further reduced glomerular matrix accumulation. In addition, even in the absence of RAGE expression, alagebrium attenuated cortical inflammation, as denoted by the reduced expression of monocyte chemoattractant protein-1, intracellular adhesion molecule-1, and the macrophage marker cluster of differentiation molecule 11b. These novel findings confirm the presence of important RAGE-independent as well as RAGE-dependent signaling pathways that may be activated in the kidney by AGEs. This has important implications for the design of optimal therapeutic strategies for the prevention of diabetic nephropathy.

Watson, Anna M.D.; Gray, Stephen P.; Jiaze, Li; Soro-Paavonen, Aino; Wong, Benedict; Cooper, Mark E.; Bierhaus, Angelika; Pickering, Raelene; Tikellis, Christos; Tsorotes, Despina; Thomas, Merlin C.; Jandeleit-Dahm, Karin A.M.

2012-01-01

328

Acute effects of brain-derived neurotrophic factor on energy expenditure in obese diabetic mice  

Microsoft Academic Search

OBJECTIVE: We recently demonstrated that chronic treatment with brain-derived neurotrophic factor (BDNF) regulates energy expenditure in obese diabetic C57BL\\/KsJ-db\\/db mice. In this study, we investigated the acute effects of BDNF on energy expenditure.DESIGN: After BDNF was singly administered to male db\\/db mice (aged 10–12 weeks), their body temperature and whole body glucose oxidation were measured. Their norepinephrine (NE) turnover and

A Tsuchida; T Nonomura; M Ono-Kishino; T Nakagawa; M Taiji; H Noguchi

2001-01-01

329

Partial inactivation of Ankrd26 causes diabetes with enhanced insulin responsiveness of adipose tissue in mice  

Microsoft Academic Search

Aims\\/hypothesis  \\u000a ANKRD26 is a newly described gene located at 10p12 in humans, a locus that has been identified with some forms of hereditary obesity.\\u000a Previous studies have shown that partial inactivation of Ankrd26 in mice causes hyperphagia, obesity and gigantism. Hypothesising that Ankrd26 mutant (MT) mice could develop diabetes, we sought to establish whether the observed phenotype could be (1)

G. A. Raciti; T. K. Bera; O. Gavrilova; I. Pastan

330

Improvement of glucose homeostasis in obese diabetic db\\/db mice given Plasmodium yoelii glycosylphosphatidylinositols  

Microsoft Academic Search

We have previously reported that infection with Plasmodium yoelii, Plasmodium chabaudi, or injection of extracts from malaria-parasitized red blood cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in streptozotocin (STZ)-diabetic mice. P yoelii glycosylphosphatidylinositols (GPIs) were extracted in chloroform:methanol:water (CMW) (10:10:3), purified by high-performance thin layer chromatography (HPTLC) and tested for their insulin-mimetic activities. The effects of P

K. M Elased; K. A Gumaa; J. B de Souza; J. H. L Playfair; T. W Rademacher

2004-01-01

331

Diabetic neuropathy in db\\/db mice develops independently of changes in ATPase and aldose reductase  

Microsoft Academic Search

Summary  ATPase activity was investigated in sciatic and optic nerves of female mutant diabetic C57Bl\\/Ks (db\\/db) mice and age-matched control mice (db\\/m and m\\/m). Nerves from animals aged 50, 70, 125, 180 and 280 days were assayed in vitro for ATPase activity in the presence or absence of ouabain: the ouabain-sensitive fraction contained Na+,K+-ATPase. Enzymatic activity was compared within and between

R. Bianchi; C. Marelli; P. Marini; M. Fabris; C. Triban; M. G. Fiori

1990-01-01

332

Diabetes accelerates retinal ganglion cell dysfunction in mice lacking sigma receptor 1  

PubMed Central

Purpose Sigma receptor 1 (?R1) is a non-opioid transmembrane protein that may act as a molecular chaperone at the endoplasmic reticulum–mitochondrial membrane. Ligands for ?R1, such as (+)-pentazocine [(+)-PTZ], confer marked retinal neuroprotection in vivo and in vitro. Recently we analyzed the retinal phenotype of mice lacking ?R1 (?R1 KO) and observed normal retinal morphology and function in young mice (5–30 weeks) but diminished negative scotopic threshold responses (nSTRs), retinal ganglion cell (RGC) loss, and disruption of optic nerve axons consistent with inner retinal dysfunction by 1 year. These data led us to test the hypothesis that ?R1 may be critical in forestalling chronic retinal stress; diabetes was used as the model of chronic stress. Methods To determine whether ?R1 is required for (+)-PTZ neuroprotective effects, primary RGCs isolated from wild-type (WT) and ?R1 KO mice were exposed to xanthine–xanthine oxidase (10 µM:2 mU/ml) to induce oxidative stress in the presence or absence of (+)-PTZ. Cell death was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. To assess effects of chronic stress on RGC function, diabetes was induced in 3-week C57BL/6 (WT) and ?R1 KO mice, using streptozotocin to yield four groups: WT nondiabetic (WT non-DB), WT diabetic (WT-DB), ?R1 KO non-DB, and ?R1 KO-DB. After 12 weeks of diabetes, when mice were 15-weeks old, intraocular pressure (IOP) was recorded, electrophysiologic testing was performed (including detection of nSTRs), and the number of RGCs was counted in retinal histological sections. Results In vitro studies showed that (+)-PTZ could not prevent oxidative stress-induced death of RGCs harvested from ?R1 KO mice but afforded robust protection against death of RGCs harvested from WT mice. In the studies of chronic stress induced by diabetes, the IOP measured in the four mouse groups was within the normal range; however, there was a significant increase in the IOP of ?R1 KO-DB mice (16±0.5 mmHg) compared to the other groups tested (?R1 KO non-DB, WT non-DB, WT-DB: ~12±0.6 mmHg). Regarding electrophysiologic testing, the nSTRs of ?R1 KO non-DB mice were similar to WT non-DB mice at 15 weeks; however, they were significantly lower in ?R1 KO-DB mice (5±1 µV) compared to the other groups, including, notably, ?R1 KO-nonDB (12±2 µV). As expected, the number of RGCs in ?R1 KO non-DB mice was similar to WT non-DB mice at 15 weeks, but under chronic stress of diabetes there were fewer RGCs in retinas of ?R1 KO-DB mice. Conclusions This is the first report showing unequivocally that the neuroprotective effects of (+)-PTZ require ?R1. ?R1 KO mice show normal retinal structure and function at young ages; however, when subjected to the chronic stress of diabetes, there is an acceleration of retinal functional deficits in ?R1 KO mice such that ganglion cell dysfunction is observed at a much earlier age than nondiabetic ?R1 KO mice. The data support the hypothesis that ?R1 plays a key role in modulating retinal stress and may be an important target for retinal disease.

Ha, Yonju; Saul, Alan; Tawfik, Amany; Zorrilla, Eric P.; Ganapathy, Vadivel

2012-01-01

333

Vasopeptidase inhibitor ilepatril (AVE7688) prevents obesity- and diabetes-induced neuropathy in C57Bl/6J mice.  

PubMed

Previously we demonstrated that inhibition of neutral endopeptidase (NEP), a protease that degrades vaso- and neuro-active peptides, and angiotensin converting enzyme (ACE) with a vasopeptidase inhibitor improves vascular and neural function in diabetic rat models. The purpose of this study was to determine whether inhibition of NEP and ACE or deletion of NEP provides protection from nerve impairment caused by diabetes or diet induced obesity (DIO). To determine the role of NEP and ACE inhibition in neuropathy related to insulin-deficient diabetes or DIO we used C57Bl/6J mice treated with AVE7688, a vasopeptidase inhibitor, or NEP deficient (-/-) mice. Mice at 12 weeks of age were fed a high fat diet for 12 weeks or were diabetic for duration of 12 weeks following a single injection of high dose streptozotocin. Both a prevention and intervention protocol was used for AVE7688 treatment. Glucose utilization was impaired in DIO C57Bl/6J and NEP -/- mice. However, treating DIO C57Bl/6J or NEP -/- mice with AVE7688 improved glucose tolerance. Thermal hypoalgesia and nerve conduction slowing were present in both streptozotocin-diabetic and DIO C57Bl/6J mice but not in AVE7688 treated C57Bl/6J mice or NEP -/- mice exposed to either streptozotocin-induced diabetes or a high fat diet. Intraepidermal nerve fiber (IENF) profiles were decreased in the hindpaw of C57Bl/6J diabetic or DIO mice and this improved when the mice were treated with AVE7688. IENF profiles were not decreased in diabetic or DIO NEP (-/-) mice. These studies suggest that NEP plays a role in regulating nerve function in insulin-deficient diabetes and DIO. PMID:20849865

Coppey, Lawrence; Davidson, Eric; Lu, Bao; Gerard, Craig; Yorek, Mark

2010-09-16

334

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.

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

2011-01-01

335

Impaired response of experimental diabetic mice to tricyclics: a possible beta-adrenergic mechanism.  

PubMed

Diabetes is reportedly associated with alterations in peripheral and central noradrenergic systems. The latter might be involved in the antidepressant effects of imipramine-like drugs in both humans and animals. Therefore, it is possible that diabetics show an impaired responsiveness to tricyclics. To test this possibility the effects of streptozotocin (STZ)-induced experimental diabetes in mice were assessed in two psychopharmacological tests: 1) the reversal of apomorphine- (16 mg/kg) induced hypothermia and 2) the hypoactivity induced by a direct beta-agonist (clenbuterol 0.06 mg/kg). At day 15 after STZ or vehicle treatment, imipramine (4 mg/kg) antagonized the apomorphine-induced hypothermia in diabetic (D) and nondiabetic (ND) mice and clenbuterol produced hypoactivity in both groups. At day 30 and 45, the ability of imipramine (1, 2, 4, 8, 16 mg/kg), clomipramine (8 mg/kg) and desipramine (2 mg/kg) to reverse apomorphine-induced hypothermia disappeared at the same time that clenbuterol lost its ability to induce hypomotility in D mice. These impaired responses on both tests were corrected by a short period of insulin therapy. These two tests may reflect central beta-adrenergic functions. Therefore, these data suggest that the impaired responsiveness of diabetic mice might be due at least in part to a noradrenergic dysfunction. Possibly, in diabetes, a beta-adrenoceptor desensitization identical to that observed at the peripheral level occurs in the central nervous system. The possibility that a thyroid hormone deficiency may be involved was also tested. Decreased T3 plasma levels were found in D mice concomitant with the impaired pharmacological responses and T3 supplementation turned these responses to normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2855269

Massol, J; Martin, P; Chatelain, F; Soubrié, P; Puech, A J

1988-12-01

336

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.

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

2011-01-01

337

Exacerbated Brain Damage, Edema and Inflammation in Type-2 Diabetic Mice Subjected to Focal Ischemia  

PubMed Central

One of the limiting factors in stroke therapeutic development is the use of animal models that do not well represent the underlying medical conditions of patients. In humans, diabetes increases the risk of stroke incidence as well as post-stroke mortality. To understand the mechanisms that render diabetics to increased brain damage, we evaluated the effect of transient middle cerebral artery occlusion (MCAO) in adult db/db mice. The db/db mouse is a model of type-2 diabetes with 4 times higher blood sugar than its normoglycemic genetic control (db/+ mouse). Following transient MCAO, the db/db mice showed significantly higher mortality, bigger infarcts, increased cerebral edema, worsened neurological status compared to db/+ mice. The db/db mice also showed significantly higher post-ischemic inflammatory markers (ICAM1+ capillaries, extravasated macrophages/neutrophils and exacerbated proinflammatory gene expression) compared to db/+ mice. In addition, the post-ischemic neuroprotective heat-shock chaperone gene expression was curtailed in the db/db compared to db/+ mice.

Tureyen, Kudret; Bowen, Kellie; Liang, Jin; Dempsey, Robert J; Vemuganti, Raghu

2010-01-01

338

Mesenchymal stem cells facilitate mixed hematopoietic chimerism induction and prevent onset of diabetes in NOD mice  

PubMed Central

Objectives Allogeneic mesenchymal stem cells (MSCs) and bone marrow cells (BMCs) were co-transplanted in NOD mice following none myeloablative preconditioning and the development of chimerism, insulitis, diabetes, and graft versus host disease (GVHD) were monitored. Methods Eight-weeks-old female NOD mice were injected intravenously with 2×107 BMCs and 5×105 MSCs from C57BL/6 mice following treatment with 2 intraperitoneal injections of anti-CD3 antibody (days ?7 and ?4), and 3Gy total body irradiation (day ?1). Thereafter, blood glucose and chimerism were monitored on peripheral blood samples. Results Stable mixed chimerism (3->90% of donor phenotype) was induced in 63.2% of BMCs-MSCs-(n=19) and 45.0% of BMCs alone recipients (n=20, p=0.256). Insulitis was prevented and euglycemia persisted for >18 weeks in 89.5% of BMCs-MSCs recipients including those with <3% chimerism and 55% of BM alone recipients (p<0.05). In controls, 9.1% of mice receiving preconditioning treatment alone (n=11) and 16.7% of preconditioned mice receiving only MSCs (n=12) were non-diabetic. GVHD was not detected in all mice. Conclusion Co-injection of MSCs and BMCs increased the success rate in inducing chimerism and preventing insulitis and overt diabetes with no incidence of GVHD. Results also indicated that even micro-chimerism with <3% donor cells is sufficient for blocking autoimmunity.

Asari, Sadaki; Itakura, Shin; Rawson, Jeffrey; Ito, Taihei; Todorov, Ivan; Nair, Indu; Shintaku, Jonathan; Liu, Chih-Pin; Kandeel, Fouad; Mullen, Yoko

2011-01-01

339

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

340

Sulfaphenazole treatment restores endothelium-dependent vasodilation in diabetic mice  

Microsoft Academic Search

Vascular dysfunction is linked with increased free radical generation and is a major contributor to the high mortality rates observed in diabetes. Several probable sources of free radical generation have been suggested in diabetes, including cytochrome P450 (CYP) monooxygenase-dependent pathways. CYP-mediated superoxide production reduces nitric oxide (NO) bioavailability. In this study, we focus on the contribution of monooxygenase enzyme-generated reactive

Shahrzad Elmi; Nada A. Sallam; Mohammad M. Rahman; Xiaowei Teng; Arwen L. Hunter; Farzad Moien-Afshari; Majid Khazaei; David J. Granville; Ismail Laher

2008-01-01

341

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

PubMed

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

2013-08-18

342

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.

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

2013-01-01

343

Reversal of type 2 diabetes in mice by products of malaria parasites: I. Effect of inactivated parasites  

Microsoft Academic Search

C57BL\\/KsJ-db\\/db and C57BL\\/KsJ-ob\\/ob mice are good models for studies on human obesity and type 2 diabetes. We have previously shown that infection with blood-stage malaria or injection of extracts from malaria-parasitized red blood cells induces hypoglycemia in normal mice and normalizes hyperglycemia in mice made moderately diabetic by streptozotocin. In the present study, we show that a single intravenous (IV)

K. M. Elased; J. B. de Souza; J. H. L. Playfair

2000-01-01

344

Antidiabetic and antioxidant effects of Picrorhiza kurrooa rhizome extracts in diabetic rats.  

PubMed

Picrorhiza kurrooa is mentioned in Ayurveda for the treatment of many disorders, but it has not been subjected to systematic scientific investigations to assess its antidiabetic effect. The oral administration of aqueous and methanol extracts of P. kurrooa rhizomes (250 and 500 mg / kg body weight / day) for 15 days significantly reduced blood glucose, glycosylated haemoglobin and increased total hemoglobin, plasma insulin in alloxan-induced diabetes in albino rats. The treatment also showed significant correction in the level of nitric oxide radicals, superoxide radicals, peroxynitrite radical, lipid peroxidation, glutathione, glutathione reductase, glutathione-S-transferase, glutathione peroxidase, superoxide dismutase and catalase in the pancreas of alloxan diabetic rats. PMID:23105761

Chauhan, Shivkumar; Nath, Nirmalendu; Tule, Vinay

2008-10-01

345

DNA oxidation and superoxide dismutase in the kidney of diabetic animals: effects of pioglitazone and repaglinide  

Microsoft Academic Search

In the present study, DNA oxidative damage was elevated and superoxide dismutase (Cu,Zn-SOD) metabolism was disturbed in the\\u000a kidney of alloxan-induced diabetic animals. The effects of pioglitazone and repaglinide, new oral antidiabetics, on 8-hydroxy-2?-deoxyguanosine\\u000a (8-OHdG) and Cu,Zn-SOD were studied. Diabetic versus control levels (mean ± SE) of 8-OHdG were 24.9 ± 0.2 vs. 21.8 ± 0.1 and\\u000a 21.5 ± 0.2

Anna Gumieniczek; Hanna Hopka?a; Jolanta Rzymowska; Maciej Niemczyk

2006-01-01

346

Hyperactivity of ON-Type Retinal Ganglion Cells in Streptozotocin-Induced Diabetic Mice  

PubMed Central

Impairment of visual function has been detected in the early stage of diabetes but the underlying neural mechanisms involved are largely unknown. Morphological and functional alterations of retinal ganglion cells, the final output neurons of the vertebrate retina, are thought to be the major cause of visual defects in diabetes but direct evidence to support this notion is limited. In this study we investigated functional changes of retinal ganglion cells in a type 1-like diabetic mouse model. Our results demonstrated that the spontaneous spiking activity of ON-type retinal ganglion cells was increased in streptozotocin-diabetic mice after 3 to 4 months of diabetes. At this stage of diabetes, no apoptotic signals or cell loss were detected in the ganglion cell layer of the retina, suggesting that the functional alterations in ganglion cells occur prior to massive ganglion cell apoptosis. Furthermore, we found that the increased activity of ON-type ganglion cells was mainly a result of reduced inhibitory signaling to the cells in diabetes. This novel mechanism provides insight into how visual function is impaired in diabetic retinopathy.

Yu, Jun; Wang, Lu; Weng, Shi-Jun; Yang, Xiong-Li; Zhang, Dao-Qi; Zhong, Yong-Mei

2013-01-01

347

Hypertension and disrupted blood pressure circadian rhythm in type 2 diabetic db/db mice.  

PubMed

Human Type 2 diabetes is associated with increased incidence of hypertension and disrupted blood pressure (BP) circadian rhythm. Db/db mice have been used extensively as a model of Type 2 diabetes, but their BP is not well characterized. In this study, we used radiotelemetry to define BP and the circadian rhythm in db/db mice. We found that the systolic, diastolic, and mean arterial pressures were each significantly increased by 11, 8, and 9 mmHg in db/db mice compared with controls. In contrast, no difference was observed in pulse pressure or heart rate. Interestingly, both the length of time db/db mice were active (locomotor) and the intensity of locomotor activity were significantly decreased in db/db mice. In contrast to controls, the 12-h light period average BP in db/db mice did not dip significantly from the 12-h dark period. A partial Fourier analysis of the continuous 72-h BP data revealed that the power and the amplitude of the 24-h period length rhythm were significantly decreased in db/db mice compared with the controls. The acrophase was centered at 0141 in control mice, but became scattered from 1805 to 0236 in db/db mice. In addition to BP, the circadian rhythms of heart rate and locomotor activity were also disrupted in db/db mice. The mean arterial pressure during the light period correlates with plasma glucose, insulin, and body weight. Moreover, the oscillations of the clock genes DBP and Bmal1 but not Per1 were significantly dampened in db/db mouse aorta compared with controls. In summary, our data show that db/db mice are hypertensive with a disrupted BP, heart rate, and locomotor circadian rhythm. Such changes are associated with dampened oscillations of clock genes DBP and Bmal1 in vasculature. PMID:18708447

Su, Wen; Guo, Zhenheng; Randall, David C; Cassis, Lisa; Brown, David R; Gong, Ming C

2008-08-15

348

Proteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation.  

PubMed

The non-enzymatic reaction between glucose and protein can be chemically reversed by transglycation. Here we report the transglycation activity of hydralazine using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in streptozotocin (STZ) induced diabetic mice, as evidenced by decrease in protein glycation, as well as presence of hydralazine-glucose conjugate in urine of diabetic mice treated with hydralazine. Hydralazine down regulated the expression of Receptor for Advanced Glycation End products (RAGE), NADPH oxidase (NOX), and super oxide dismutase (SOD). These findings will provide a new dimension for developing intervention strategies for the treatment of glycation associated diseases such as diabetes complications, atherosclerosis, and aging. PMID:24126953

Kesavan, Suresh K; Bhat, Shweta; Golegaonkar, Sandeep B; Jagadeeshaprasad, Mashanipalya G; Deshmukh, Arati B; Patil, Harshal S; Bhosale, Santosh D; Shaikh, Mahemud L; Thulasiram, Hirekodathakallu V; Boppana, Ramanamurthy; Kulkarni, Mahesh J

2013-10-15

349

Proteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation  

PubMed Central

The non-enzymatic reaction between glucose and protein can be chemically reversed by transglycation. Here we report the transglycation activity of hydralazine using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in streptozotocin (STZ) induced diabetic mice, as evidenced by decrease in protein glycation, as well as presence of hydralazine-glucose conjugate in urine of diabetic mice treated with hydralazine. Hydralazine down regulated the expression of Receptor for Advanced Glycation End products (RAGE), NADPH oxidase (NOX), and super oxide dismutase (SOD). These findings will provide a new dimension for developing intervention strategies for the treatment of glycation associated diseases such as diabetes complications, atherosclerosis, and aging.

Kesavan, Suresh K.; Bhat, Shweta; Golegaonkar, Sandeep B.; Jagadeeshaprasad, Mashanipalya G.; Deshmukh, Arati B.; Patil, Harshal S.; Bhosale, Santosh D.; Shaikh, Mahemud L.; Thulasiram, Hirekodathakallu V.; Boppana, Ramanamurthy; Kulkarni, Mahesh J.

2013-01-01

350

The Programmed Death1 (PD1) Pathway Regulates Autoimmune Diabetes in Nonobese Diabetic (NOD) Mice  

Microsoft Academic Search

Programmed death-1 (PD-1) receptor, an inhibitory costimulatory molecule found on acti- vated T cells, has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated the role of this pathway in the development of autoim- mune diabetes. PD-1 or PD-L1 but not PD-L2 blockade rapidly precipitated diabetes in predi- abetic female nonobese diabetic

Mohammed Javeed; I. Ansari; Alan D. Salama; Tanuja Chitnis; R. Neal Smith; Hideo Yagita; Hisaya Akiba; Tomohide Yamazaki; Miyuki Azuma; Hideyuki Iwai; Samia J. Khoury; Hugh Auchincloss; Mohamed H. Sayegh

2003-01-01

351

Macrophage Dysfunction Impairs Resolution of Inflammation in the Wounds of Diabetic Mice  

PubMed Central

Background Chronic inflammation is a characteristic feature of diabetic cutaneous wounds. We sought to delineate novel mechanisms involved in the impairment of resolution of inflammation in diabetic cutaneous wounds. At the wound-site, efficient dead cell clearance (efferocytosis) is a pre-requisite for the timely resolution of inflammation and successful healing. Methodology/Principal Findings Macrophages isolated from wounds of diabetic mice showed significant impairment in efferocytosis. Impaired efferocytosis was associated with significantly higher burden of apoptotic cells in wound tissue as well as higher expression of pro-inflammatory and lower expression of anti-inflammatory cytokines. Observations related to apoptotic cell load at the wound site in mice were validated in the wound tissue of diabetic and non-diabetic patients. Forced Fas ligand driven elevation of apoptotic cell burden at the wound site augmented pro-inflammatory and attenuated anti-inflammatory cytokine response. Furthermore, successful efferocytosis switched wound macrophages from pro-inflammatory to an anti-inflammatory mode. Conclusions/Significance Taken together, this study presents first evidence demonstrating that diabetic wounds suffer from dysfunctional macrophage efferocytosis resulting in increased apoptotic cell burden at the wound site. This burden, in turn, prolongs the inflammatory phase and complicates wound healing.

Khanna, Savita; Biswas, Sabyasachi; Shang, Yingli; Collard, Eric; Azad, Ali; Kauh, Courtney; Bhasker, Vineet; Gordillo, Gayle M.; Sen, Chandan K.; Roy, Sashwati

2010-01-01

352

Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging  

PubMed Central

All juvenile NOD mice exhibit insulitis, but there is substantial variation in their progression to diabetes. We demonstrate that a patient-validated magnetic-resonance-imaging (MRI) strategy to non-invasively visualize local effects of pancreatic-islet inflammation can predict diabetes onset in NOD mice. MRI signals acquired during a narrow early time-window allowed pre-sorting into disease-progressors and -nonprogressors and an estimate of time-to-diabetes. We exploited this capability to identify novel elements correlated with disease protection, including CRIg (complement receptor of the immunoglobulin superfamily), which marked a subset of macrophages associated with diabetes resistance. Administration of CRIg-Fc depressed MRI signals and diabetes incidence. In addition to identifying regulators of disease progression, this study shows that diabetes is set at an early age in NOD mice.

Fu, Wenxian; Wojtkiewicz, Gregory; Weissleder, Ralph; Benoist, Christophe; Mathis, Diane

2012-01-01

353

CXC Chemokine Ligand 10 DNA Vaccination Plus Complete Freund's Adjuvant Reverses Hyperglycemia in Non-Obese Diabetic Mice  

PubMed Central

OBJECTIVE: Complete Freund's Adjuvant (CFA) is known to arrest autoimmune diabetes development in non-obese diabetic (NOD) mice. However, CFA alone cannot induce effective remission in diabetic NOD mice. Previously, we reported that anti-CXC chemokine ligand 10 (CXCL10) antibody can promote beta-cell proliferation in NOD mice. In the present study, we aimed to examine whether anti-CXCL10 plus CFA treatment can effectively reverse autoimmune diabetes development. METHODS: Systemic supply of anti-CXCL10 antibody by CXCL10 DNA vaccination in combination with CFA injection was performed in new-onset diabetic NOD mice. Remission rate of diabetes, histological characteristics of residual insulitis lesions, residual beta-cell mass, and regulatory T cell population in local pancreas were examined. RESULTS: A high frequency of diabetes reversal was observed after combination treatment with anti-CXCL10 plus CFA. In mice showing diabetes reversal, residual beta-cell mass was significantly increased, and some beta-cells were in a proliferative state. Although systemic cytokine profiles were unaffected, the frequency of "hybrid regulatory T cells", i.e. regulatory T cells expressing CXCR3, was significantly increased in local pancreatic lesions. This was possibly associated with the regulation of anti-islet autoimmunity. CONCLUSIONS: Anti-CXCL10 plus appropriate immune adjuvant therapy arrested, and reversed, type 1 diabetes development.

Oikawa, Yoichi; Shimada, Akira; Yamada, Yoshifumi; Okubo, Yoshiaki; Katsuki, Takeshi; Shigihara, Toshikatsu; Miyazaki, Jun-ichi; Narumi, Shosaku; Itoh, Hiroshi

2010-01-01

354

Integrin ?1/Akita double knockout mice on a Balb/c background develop advanced features of human diabetic nephropathy  

PubMed Central

Animal models that mimic human diabetic nephropathy are useful to identify key factors in pathogenesis of this disease as well as the development of new therapies. Several mouse models of diabetes have features of human diabetic nephropathy, yet none of these completely fulfill the Animal Models of Diabetes Complications Consortium criteria and completely reproduce pathological and functional features of the human disease. The Akita mouse carries a mutation in the insulin 2 gene and, to date, only survive as heterozygotes that develop spontaneous type 1 diabetes. Here we show that Akita mice with mutation of both insulin 2 alleles (Akita knockout (KO)) survive if crossed onto the Balb/c background. These mice develop hyperglycemia, more severe albuminuria and mesangial sclerosis compared to heterozygous mice on the same genetic background. Interestingly, crossing these AkitaKO mice with integrin ?1KO mice, a model of exacerbated glomerulosclerosis after injury and also on the Balb/c background, resulted in a 16-fold increase in albuminuria, significant mesangial matrix expansion, nodular and diffuse glomerulosclerosis, and a 2-fold increase in glomerular basement membrane thickening when compared to non-diabetic mice. Moreover a significant decline in glomerular filtration was evident in the ?1KOAkitaKO mice at 6 months of age. Thus, the integrin ?1KOAkitaKO Balb/c mouse represents a promising model presenting with most features of human diabetic nephropathy.

Yu, Ling; Su, Yan; Paueksakon, Paisit; Cheng, Huifang; Chen, Xiwu; Wang, Hongtao; Harris, Raymond C.; Zent, Roy; Pozzi, Ambra

2012-01-01

355

Losartan and Ozagrel reverse retinal arteriolar constriction in non-obese diabetic mice  

PubMed Central

Objective Reductions in retinal blood flow are observed early in diabetes. Venules may influence arteriolar constriction and flow; therefore, we hypothesized that diabetes would induce the constriction of arterioles that are in close proximity to venules, with the constriction mediated by thromboxane and angiotensin II. Methods Using non-obese diabetic (NOD) mice, retinal measurements were performed 3 weeks following the age at which glucose levels exceeded 200 mg/dl, with accompanying experiments on age-matched normoglycemic NOD mice. The measurements included retinal arteriolar diameters and red blood cell velocities, and were repeated following an injection of the thromboxane synthase inhibitor Ozagrel. Mice were subdivided into equal groups given drinking water with or without the angiotensin II receptor antagonist Losartan. Results Retinal arterioles were constricted in hyperglycemic mice, with a significant reduction in flow. However, not all arterioles were equally affected; the vasoconstriction was limited to arterioles that were in closer proximity to venules. The arteriolar vasoconstriction (mean arteriolar diameters = 51 ± 1 ?m vs 61 ± 1 ?m in controls; p<0.01) was eliminated by both Ozagrel (61 ± 2 ?m) and Losartan (63 ± 2 ?m). Conclusion Venule-dependent arteriolar vasoconstriction in NOD mice is mediated by thromboxane and/or angiotensin II.

Lee, Seungjun; Harris, Norman R.

2008-01-01

356

Dietary Epicatechin Promotes Survival of Obese Diabetic Mice and Drosophila melanogaster123  

PubMed Central

The lifespan of diabetic patients is 7–8 y shorter than that of the general population because of hyperglycemia-induced vascular complications and damage to other organs such as the liver and skeletal muscle. Here, we investigated the effects of epicatechin, one of the major flavonoids in cocoa, on health-promoting effects in obese diabetic (db/db) mice (0.25% in drinking water for 15 wk) and Drosophila melanogaster (0.01–8 mmol/L in diet). Dietary intake of epicatechin promoted survival in the diabetic mice (50% mortality in diabetic control group vs. 8.4% in epicatechin group after 15 wk of treatment), whereas blood pressure, blood glucose, food intake, and body weight gain were not significantly altered. Pathological analysis showed that epicatechin administration reduced the degeneration of aortic vessels and blunted fat deposition and hydropic degeneration in the liver caused by diabetes. Epicatechin treatment caused changes in diabetic mice that are associated with a healthier and longer lifespan, including improved skeletal muscle stress output, reduced systematic inflammation markers and serum LDL cholesterol, increased hepatic antioxidant glutathione concentration and total superoxide dismutase activity, decreased circulating insulin-like growth factor-1 (from 303 ± 21 mg/L in the diabetic control group to 189 ± 21 mg/L in the epicatechin-treated group), and improved AMP-activated protein kinase-? activity in the liver and skeletal muscle. Consistently, epicatechin (0.1–8 mmol/L) also promoted survival and increased mean lifespan of Drosophila. Therefore, epicatechin may be a novel food-derived, antiaging compound.

Si, Hongwei; Fu, Zhuo; Babu, Pon Velayutham Anandh; Zhen, Wei; LeRoith, Tanya; Meaney, Mary Pat; Voelker, Kevin A.; Jia, Zhenquan; Grange, Robert W.; Liu, Dongmin

2011-01-01

357

Prevention of Autoimmune Diabetes and Induction of ?-Cell Proliferation in NOD Mice by Hyperbaric Oxygen Therapy  

PubMed Central

We evaluated the effects of hyperbaric oxygen therapy (HOT) on autoimmune diabetes development in nonobese diabetic (NOD) mice. Animals received no treatment or daily 60-min HOT 100% oxygen (HOT-100%) at 2.0 atmospheres absolute and were monitored for diabetes onset, insulitis, infiltrating cells, immune cell function, and ?-cell apoptosis and proliferation. Cyclophosphamide-induced diabetes onset was reduced from 85.3% in controls to 48% after HOT-100% (P < 0.005) and paralleled by lower insulitis. Spontaneous diabetes incidence reduced from 85% in controls to 65% in HOT-100% (P = 0.01). Prediabetic mice receiving HOT-100% showed lower insulitis scores, reduced T-cell proliferation upon stimulation in vitro (P < 0.03), increased CD62L expression in T cells (P < 0.04), reduced costimulation markers (CD40, DC80, and CD86), and reduced major histocompatibility complex class II expression in dendritic cells (DCs) (P < 0.025), compared with controls. After autoimmunity was established, HOT was less effective. HOT-100% yielded reduced apoptosis (transferase-mediated dUTP nick-end labeling-positive insulin-positive cells; P < 0.01) and increased proliferation (bromodeoxyuridine incorporation; P < 0.001) of insulin-positive cells compared with controls. HOT reduces autoimmune diabetes incidence in NOD mice via increased resting T cells and reduced activation of DCs with preservation of ?-cell mass resulting from decreased apoptosis and increased proliferation. The safety profile and noninvasiveness makes HOT an appealing adjuvant therapy for diabetes prevention and intervention trials.

Faleo, Gaetano; Fotino, Carmen; Bocca, Nicola; Molano, R. Damaris; Zahr-Akrawi, Elsie; Molina, Judith; Villate, Susana; Umland, Oliver; Skyler, Jay S.; Bayer, Allison L.; Ricordi, Camillo; Pileggi, Antonello

2012-01-01

358

Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice  

NASA Astrophysics Data System (ADS)

Farnesoid X receptor (FXR) plays an important role in maintaining bile acid and cholesterol homeostasis. Here we demonstrate that FXR also regulates glucose metabolism. Activation of FXR by the synthetic agonist GW4064 or hepatic overexpression of constitutively active FXR by adenovirus-mediated gene transfer significantly lowered blood glucose levels in both diabetic db/db and wild-type mice. Consistent with these data, FXR null mice exhibited glucose intolerance and insulin insensitivity. We further demonstrate that activation of FXR in db/db mice repressed hepatic gluconeogenic genes and increased hepatic glycogen synthesis and glycogen content by a mechanism that involves enhanced insulin sensitivity. In view of its central roles in coordinating regulation of both glucose and lipid metabolism, we propose that FXR agonists are promising therapeutic agents for treatment of diabetes mellitus. glucose | GW4064 | farnesoid X receptor-VP16 | triglyceride | cholesterol

Zhang, Yanqiao; Lee, Florence Ying; Barrera, Gabriel; Lee, Hans; Vales, Charisse; Gonzalez, Frank J.; Willson, Timothy M.; Edwards, Peter A.

2006-01-01

359

Radioiodinated Naphthylalanine Derivatives Targeting Pancreatic Beta Cells in Normal and Nonobese Diabetic Mice  

PubMed Central

An imaging method capable of using a signal from pancreatic beta cells to determine their mass would be of immense value in monitoring the progression of diabetes as well as response to treatment. Somatostatin receptors (SSTRs) are expressed on beta cells and are a potential target for imaging. The main objective of this study was to investigate whether pancreatic beta cells are a target for radiolabeled naphthylalanine derivatives. The molecules were subjected to in vitro and ex vivo evaluations. Pancreatic uptake of radioactivity was lower in nonobese diabetic (NOD) mice than normal mice at all time points investigated (P < .05) and correlated with the number of islets in tissue sections of both control and NOD mice. Immunohistochemical and confocal fluorescent microscopic studies showed colocalization of insulin and the conjugate radioligand in the pancreas. The results demonstrated that pancreatic uptake is receptor-mediated, and that beta cells are the primary target.

Amartey, John K.; Shi, Yufei; Al-Jammaz, Ibrahim; Esguerra, Celestina; Al-Otaibi, Basem; Al-Mohanna, Futwan

2008-01-01

360

Loss of ACE2 accelerates time-dependent glomerular and tubulointerstitial damage in streptozotocin-induced diabetic mice.  

PubMed

As angiotensin-converting enzyme-2 (ACE2) was identified as a negative regulator of the renin-angiotensin system, there have been many reports concerning its role in several tissues, including the kidney. However, the role of ACE2 during the development of diabetic nephropathy remains undetermined, as previous reports did not necessarily support a protective role against renal injury. Thus, we performed detailed observations of kidneys in ACE2-knockout (ACE2-KO) mice at early (4 weeks) and advanced (18 weeks) stages of diabetes. ACE2-KO and wild-type C57BL/6 mice were rendered diabetic by intraperitoneal injection of streptozotocin. Diabetic ACE2-KO mice showed earlier onset and more severe progression of albuminuria than those did wild-type mice. The elevation of serum creatinine and urea nitrogen levels at 18 weeks of diabetes was more prominent in ACE2-KO mice. Periodic acid-Schiff-stained cross-section of diabetic ACE2-KO mice showed a more severe time-dependent increase in glomerular/tubulointerstitial damage than did that of wild-type mice, confirmed by the immunostaining of alpha-smooth muscle actin, collagen IV and F4-80 antigen. Glomeruli of diabetic ACE2-KO mice showed earlier and more severe decrease in the expression of nephrin, whose degradation is involved in the onset of albuminuria, and more potent increase of vascular endothelial growth factor expression. In addition, treatment with AT1 receptor blocker olmesartan significantly, but not totally, ameliorated the functional and morphological deterioration of diabetic nephropathy in ACE2-KO mice. These results suggest that ACE2 might continuously protect from both glomerular and tubulointerstitial injury during the development of diabetic nephropathy. The renal-protective effect of ACE2 might involve more than just suppressing angiotensin II-mediated AT1 receptor signaling. PMID:20186149

Shiota, Atsushi; Yamamoto, Koichi; Ohishi, Mitsuru; Tatara, Yuji; Ohnishi, Miyuki; Maekawa, Yoshihiro; Iwamoto, Yoshihiro; Takeda, Masao; Rakugi, Hiromi

2010-02-26

361

Downregulation of adipose triglyceride lipase in the heart aggravates diabetic cardiomyopathy in db/db mice.  

PubMed

Adipose triglyceride lipase (ATGL) was recently identified as a rate-limiting triglyceride (TG) lipase and its activity is stimulated by comparative gene identification-58 (CGI-58). Mutations in the ATGL or CGI-58 genes are associated with neutral lipid storage diseases characterized by the accumulation of TG in multiple tissues. The cardiac phenotype, known as triglyceride deposit cardiomyovasculopathy, is characterized by TG accumulation in coronary atherosclerotic lesions and in the myocardium. Recent reports showed that myocardial TG accumulation is significantly higher in patients with diabetes and is associated with impaired left ventricular diastolic function. Therefore, we investigated the roles of ATGL and CGI-58 in the development of myocardial steatosis in the diabetic state. Histological examination with oil red O staining showed marked lipid deposition in the hearts of diabetic fatty db/db mice. Cardiac triglyceride and diglyceride contents were greater in db/db mice than in db/+ control mice. Next, we determined the expression of genes and proteins that affect lipid metabolism, and found that ATGL and CGI-58 expression levels were decreased in the hearts of db/db mice. We also found increased expression of genes regulating triglyceride synthesis (sterol regulatory element-binding protein 1c, monoacylglycerol acyltransferases, and diacylglycerol acyltransferases) in db/db mice. Regarding key modulators of apoptosis, PKC activity, and oxidative stress, we found that Bcl-2 levels were lower and that phosphorylated PKC and 8-hydroxy-2'-deoxyguanosine levels were higher in db/db hearts. These results suggest that reduced ATGL and CGI-58 expression and increased TG synthesis may exacerbate myocardial steatosis and oxidative stress, thereby promoting cardiac apoptosis in diabetic mice. PMID:23886955

Inoue, Tomoaki; Kobayashi, Kunihisa; Inoguchi, Toyoshi; Sonoda, Noriyuki; Maeda, Yasutaka; Hirata, Eiichi; Fujimura, Yoshinori; Miura, Daisuke; Hirano, Ken-ichi; Takayanagi, Ryoichi

2013-07-22

362

Akita Spontaneously Type 1 Diabetic Mice Exhibit Elevated Vascular Arginase and Impaired Vascular Endothelial and Nitrergic Function  

PubMed Central

Background Elevated arginase (Arg) activity is reported to be involved in diabetes-induced vascular endothelial dysfunction. It can reduce L-arginine availability to nitric oxide (NO) synthase (NOS) and NO production. Akita mice, a genetic non-obese type 1 diabetes model, recapitulate human diabetes. We determined the role of Arg in a time-course of diabetes-associated endothelial dysfunction in aorta and corpora cavernosa (CC) from Akita mice. Methods and Results Endothelium-dependent relaxation, Arg and NOS activity, and protein expression levels of Arg and constitutive NOS were assessed in aortas and CC from Akita and non-diabetic wild type (WT) mice at 4, 12 and 24 wks of age. Systolic blood pressure (SBP) was assessed by tail cuff. In aorta and CC, Akita mice exhibited a progressive impairment of vascular endothelial and nitrergic function increased Arg activity and expression (Arg1 in aorta and both Arg1 and Arg2 in CC) compared with that of age-matched WT mice. Treatment of aorta and CC from Akita mice with an Arg inhibitor (BEC or ABH) reduced diabetes-induced elevation of Arg activity and restored endothelial and nitrergic function. Reduced levels of phospho-eNOS at Ser1177 (in aorta and CC) and nNOS expression (in CC) were observed in Akita mice at 12 and 24 wks. Akita mice also had decreased NOS activity in aorta and CC at 12 and 24 wks that was restored by BEC treatment. Further, Akita mice exhibited moderately increased SBP at 24 wks and increased sensitivity to PE-induced contractions in aorta and sympathetic nerve stimulation in CC at 12 and 24 wks. Conclusions Over 24 wks of diabetes in Akita mice, both aortic and cavernosal tissues exhibited increased Arg activity/expression, contributing to impaired endothelial and nitrergic function and reduced NO production. Our findings demonstrate involvement of Arg activity in diabetes-induced impairment of vascular function in Akita mouse.

Toque, Haroldo A.; Nunes, Kenia P.; Yao, Lin; Xu, Zhimin; Kondrikov, Dmitry; Su, Yunchao; Webb, R. Clinton; Caldwell, Ruth B.; Caldwell, R. William

2013-01-01

363

Hypoglycaemic effects of alcoholic root extract of Borassus flabellifer (Linn.) in normal and diabetic rats.  

PubMed

The objective of the study was to investigate the alcoholic (ALEBF) extract of B. flabellifer for their hypoglycaemic effects in normal and diabetic rats. Diabetes was induced in rats by single dose administration of alloxan (120 mg/kg, i.p.) or by injecting dexamethasone (10 mg/kg, i.p.) for 10 days. In normal rats, ALEBF (100, 200 and 400 mg/kg) had significantly decreased the blood glucose level in a dose dependent manner after repeated administration for 7 days. In alloxan induced diabetic rats, extract (ALEBF) had decreased blood sugar level and improved glucose tolerance in alloxan induced diabetic rats at the end of 1st, 2nd , 3rd and 4th week after test extract treatment. However, the insulin levels of extract treated group did not significantly change after 28 days treatment with the extract. It did not alter the insulin levels. In alloxan model, repeated dose administration of ALEBF had showed significant increase in body weight, prevention of elimination of sugar in urine and reduced the mortality rate induced by alloxan. In dexamethasone induced insulin resistance diabetic rats, repeated administration of ALEBF inhibited the increase in blood glucose level, improved glucose tolerance and reduced the insulin levels as compared dexamethasone induced diabetic rats. PMID:23811441

Debnath, Titas; Radhakrishnan, Rajesh; Murugananthan, Gopal; Talwar, Sahil; K, Nandakumar

2013-07-01

364

Two diallyl sulphides derived from garlic inhibit meticillin-resistant Staphylococcus aureus infection in diabetic mice.  

PubMed

The inhibitory effect of diallyl sulphide (DAS) and diallyl disulphide (DADS) against meticillin-resistant Staphylococcus aureus (MRSA) infection in diabetic mice was studied. The influence of these agents on the plasma levels of fibronectin, C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-alpha), and on the activity of plasminogen activator inhibitor-1 (PAI-1), antithrombin III (AT-III) and protein C, in MRSA-infected diabetic mice was examined. To induce diabetes, mice were treated intraperitoneally with streptozotocin for 5 consecutive days. Ten clinical MRSA isolates obtained from infected patients were used in this study. Diabetic mice were infected by injecting 200 microl MRSA/PBS suspension containing 10(7) c.f.u. via the tail vein. At day 4 post-infection, 200 microl DAS or DADS was administrated twice orally with an interval of 12 h. Eight hours after each administration, the blood and organs of mice were collected. Results showed that DAS and DADS significantly decreased MRSA viability in the kidney (P<0.05), with administration of each agent twice showing a greater inhibitory effect than when given once (P<0.05). MRSA infection in diabetic mice significantly elevated the plasma levels of IL-6 and TNF-alpha (P<0.05). DAS or DADS given once did not affect the plasma levels of IL-6 and TNF-alpha (P>0.05); however, DAS or DADS given twice significantly decreased the plasma levels of both IL-6 and TNF-alpha (P<0.05). DAS and DADS treatments also significantly reduced the plasma levels of CRP, fibronectin and fibrinogen (P<0.05). DAS or DADS treatment did not affect PAI-1 activity (P>0.05), but DAS or DADS given twice significantly increased AT-III activity (P<0.05). DADS given twice elevated protein C activity (P<0.05). MRSA infection significantly increased malondialdehyde levels in the kidney and spleen (P<0.05), and these levels were significantly decreased by treatment with DAS or DADS (P<0.05). These data suggest that DAS and DADS could provide multiple protective functions against MRSA infection in diabetic mice. PMID:17510266

Tsao, Shih-Ming; Liu, Wen-Hu; Yin, Mei-Chin

2007-06-01

365

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.

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

2013-01-01

366

Metabolic stress-induced activation of FoxO1 triggers diabetic cardiomyopathy in mice  

PubMed Central

The leading cause of death in diabetic patients is cardiovascular disease; diabetic cardiomyopathy is typified by alterations in cardiac morphology and function, independent of hypertension or coronary disease. However, the molecular mechanism that links diabetes to cardiomyopathy is incompletely understood. Insulin resistance is a hallmark feature of diabetes, and the FoxO family of transcription factors, which regulate cell size, viability, and metabolism, are established targets of insulin and growth factor signaling. Here, we set out to evaluate a possible role of FoxO proteins in diabetic cardiomyopathy. We found that FoxO proteins were persistently activated in cardiac tissue in mice with diabetes induced either genetically or by high-fat diet (HFD). FoxO activity was critically linked with development of cardiomyopathy: cardiomyocyte-specific deletion of FoxO1 rescued HFD-induced declines in cardiac function and preserved cardiomyocyte insulin responsiveness. FoxO1-depleted cells displayed a shift in their metabolic substrate usage, from free fatty acids to glucose, associated with decreased accumulation of lipids in the heart. Furthermore, we found that FoxO1-dependent downregulation of IRS1 resulted in blunted Akt signaling and insulin resistance. Together, these data suggest that activation of FoxO1 is an important mediator of diabetic cardiomyopathy and is a promising therapeutic target for the disease.

Battiprolu, Pavan K.; Hojayev, Berdymammet; Jiang, Nan; Wang, Zhao V.; Luo, Xiang; Iglewski, Myriam; Shelton, John M.; Gerard, Robert D.; Rothermel, Beverly A.; Gillette, Thomas G.; Lavandero, Sergio; Hill, Joseph A.

2012-01-01

367

INTERMITTENT INJECTIONS OF OSTEOCALCIN IMPROVE GLUCOSE METABOLISM AND PREVENT TYPE 2 DIABETES IN MICE  

PubMed Central

The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a result, the absence of osteocalcin leads to glucose intolerance in mice, while genetically modified mice with an increase in uncarboxylated osteocalcin are protected from type 2 diabetes and obesity. Here, we tested in the mouse the therapeutic potential of intermittent administration of osteocalcin. We found that daily injections of osteocalcin at either 3 or 30 ng/g/day significantly improved glucose tolerance and insulin sensitivity in mice fed a normal diet. This was attributable, in part, to an increase in both ?-cell mass and insulin secretion. When mice were fed a high-fat diet (HFD), daily injections of osteocalcin partially restored insulin sensitivity and glucose tolerance. Moreover, mice treated with intermittent osteocalcin injections displayed additional mitochondria in their skeletal muscle, had increased energy expenditure and were protected from diet-induced obesity. Finally, the hepatic steatosis induced by the HFD was completely rescued in mice receiving osteocalcin daily. Overall, these results provide evidence that daily injections of osteocalcin can improve glucose handling and prevent the development of type 2 diabetes.

Ferron, Mathieu; McKee, Marc D.; Levine, Robert L.; Ducy, Patricia; Karsenty, Gerard

2011-01-01

368

Effect of some hypoglycemic herbs on the activity of phase I and II drug-metabolizing enzymes in alloxan-induced diabetic rats  

Microsoft Academic Search

Polycyclic aromatic hydrocarbons (PAHs) and N-nitrosamines (NNA) are mainly activated by cytochrome P450s, and their associated enzyme activities such as aryl hydrocarbon (benzo(a)pyrene) hydroxylase (AHH), N-nitrosdimethylamine N-demethylase I (NDMA-dI), NADPH-cytochrome C reductase, and detoxified by glutathione S-transferase (GST) and glutathione (GSH). The present study shows the influence of Cymbopogonproximus (Halfa barr), Zygophyllumcoccineum L. (Kammun quaramany), Lupinusalbus (Termis) as herbs capable

S. A. Sheweita; A. A. Newairy; H. A. Mansour; M. I. Yousef

2002-01-01

369

Gene expression profiles define a key checkpoint for type 1 diabetes in NOD mice.  

PubMed

cDNA microarrays with >11,000 cDNA clones from an NOD spleen cDNA library were used to identify temporal gene expression changes in NOD mice (1-10 weeks), which spontaneously develop type 1 diabetes, and changes between NOD and NOD congenic mice (NOD.Idd3/Idd10 and NOD.B10Sn-H2(b)), which have near zero incidence of insulitis and diabetes. The expression profiles identified two distinct groups of mice corresponding to an immature (1-4 weeks) and mature (6-10 weeks) state. The rapid switch of gene expression occurring around 5 weeks of age defines a key immunological checkpoint. Sixty-two known genes are upregulated, and 18 are downregulated at this checkpoint in the NOD. The expression profiles are consistent with increased antibody production, antigen presentation, and cell proliferation associated with an active autoimmune response. Seven of these genes map to confirmed diabetes susceptibility regions. Of these seven, three are excellent candidate genes not previously implicated in type 1 diabetes. Ten genes are differentially expressed between the NOD and congenic NOD at the immature stage (Hspa8, Hif1a, and several involved in cellular functions), while the other 70 genes exhibit expression differences during the mature (6-10 week) stage, suggesting that the expression differences of a small number of genes before onset of insulitis determine the disease progression. PMID:14747287

Eckenrode, Sarah E; Ruan, Qingguo; Yang, Ping; Zheng, Weipeng; McIndoe, Richard A; She, Jin-Xiong

2004-02-01

370

Age-Dependent Loss of Tolerance to an Immunodominant Epitope of Glutamic Acid Decarboxylase in Diabetic prone RIP-B7/DR4 Mice  

PubMed Central

We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice, and is accompanied by histological evidence of insulitis in the absence of overt diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4+/FoxP3+ cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice is 23% with a mean onset age of 40 weeks and is similar to that reported for RIP-B7/DR0401 mice. A gender preference is observed in that 38% of female mice become diabetic compared to 8% of male mice.

Gebe, John A.; Unrath, Kellee A; Falk, Ben A.; Ito, Kouichi; Wen, Li; Daniels, Terri L.; Lernmark, Ake; Nepom, Gerald T.

2007-01-01

371

Abnormal essential fatty acid composition of tissue lipids in genetically diabetic mice is partially corrected by dietary linoleic and gamma-linolenic acids.  

PubMed

Genetically diabetic mice (db/db) and their non-diabetic litter-mates were maintained for 15 weeks on diets supplemented with safflower oil or evening primrose (Oenothera bienis) oil, both essential fatty acid (EFA)-rich sources, or hydrogenated coconut oil (devoid of EFA). Plasma glucose was higher in the diabetic mice supplemented with the oils than in the unsupplemented diabetic mice. In the oil-supplemented non-diabetic mice, plasma glucose did not differ compared with the unsupplemented non-diabetic mice. The proportional content of arachidonic acid in the phospholipids of the pancreas was significantly decreased in diabetic mice, an effect which was completely prevented by supplementation with safflower or evening primrose oil but not hydrogenated coconut oil. In the liver phospholipids of the diabetic mice, dihomo-gamma-linolenic acid was proportionally increased, an effect reduced by supplementation with safflower oil but not evening primrose or hydrogenated coconut oils. In the liver triglycerides of the diabetic mice, gamma-linolenic acid, dihomo-gamma-linolenic acid and arachidonic acid were all proportionally decreased, effects which were also prevented by safflower or evening primrose oil but not hydrogenated coconut oil. Alopecia and dry scaly skin were prominent in the diabetic mice but less extensive in the diabetic mice supplemented with EFA. PMID:2998444

Cunnane, S C; Manku, M S; Horrobin, D F

1985-05-01

372

Reduced Alpha-Lipoic Acid Synthase Gene Expression Exacerbates Atherosclerosis in Diabetic Apolipoprotein E-Deficient Mice  

PubMed Central

Objectives To study the effects of reduced lipoic acid gene expression on diabetic atherosclerosis in apolipoprotein E null mice (Apoe?/?). Methods and Results Heterozygous lipoic acid synthase gene knockout mice (Lias+/?) crossed with Apoe?/? mice were used to evaluate the diabetic effect induced by streptozotocin on atherosclerosis in the aortic sinus of the heart. While diabetes markedly increased atherosclerotic plaque size in Apoe?/? mice, a small but significant effect of reduced expression of lipoic acid gene was observed in diabetic Lias+/?Apoe?/? mice. In the aortic lesion area, the Lias+/?Apoe?/? mice exhibited significantly increased macrophage accumulation and cellular apoptosis than diabetic Lias+/+Apoe?/? littermates. Plasma glucose, cholesterol, and interleukin-6 were also higher. These abnormalities were accompanied with increased oxidative stress including a decreased ratio of reduced glutathione/oxidized glutathione in erythrocytes, increased systemic lipid peroxidation, and increased Gpx1 and MCP1 gene expression in the aorta. Conclusions Decreased endogenous lipoic acid gene expression plays a role in development of diabetic atherosclerosis. These findings extend our understanding of the role of antioxidant in diabetic atherosclerosis.

Yi, Xianwen; Xu, Longquan; Hiller, Sylvia; Kim, Hyung-Suk; Maeda, Nobuyo

2012-01-01

373

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

374

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

PubMed

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) (40 mg/kg intraperitoneally for 5 consecutive days) to mice resulted in autoimmune diabetes. Mice were treated with methadone (10 mg/kg/day subcutaneously) for 24 days. 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)-1beta, 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. PMID:18671992

Amirshahrokhi, K; Dehpour, A R; Hadjati, J; Sotoudeh, M; Ghazi-Khansari, M

2008-07-11

375

Beneficial effects of Brazilian propolis on type 2 diabetes in ob/ob mice  

PubMed Central

The anti-diabetic effects of Brazilian propolis were examined using ob/ob mice. Although repeated injection of an ethanol extract of Brazilian propolis (100 mg/kg, ip, twice a week for 12 weeks) did not affect body weight gain and food intake of ob/ob mice, blood glucose and plasma cholesterol levels were significantly attenuated. Moreover, the propolis extract partially restored glucose tolerance and insulin resistance, indicating anti-diabetic properties of the extract. The propolis-treated mice exhibited lower weight gain in mesenteric adipose tissue, while weight gains in inguinal and epididymal adipose tissues were not modulated. Flow cytometric and microscopic analyses suggested that the extract promoted accumulation of eosinophils into mesenteric and epididymal adipose tissues. Alternatively, the ratio of M1-like macrophages to M2-like macrophages in mesenteric adipose tissue was reduced by the propolis injection, coincident with the decrement of the number of interleukin-12A+ cells. Levels of M1 macrophage markers, such as Itgax and Il12b transcripts, were decreased in the vascular stromal fraction of mesenteric adipose tissue, whereas those of pan-macrophage markers Emr1 and Cd68 were not influenced. Microarray and subsequent gene ontology term analyses suggested that propolis attenuated immune activation in mesenteric adipose tissues. Taken together, this indicates that Brazilian propolis improves diabetes in ob/ob mice, presumably through modification of immune cells in mesenteric adipose tissues.

Kitamura, Hiroshi; Naoe, Yoshinori; Kimura, Shunsuke; Miyamoto, Tomomi; Okamoto, Shiki; Toda, Chitoku; Shimamoto, Yoshinori; Iwanaga, Toshihiko; Miyoshi, Ichiro

2013-01-01

376

Weak Proinsulin Peptide-Major Histocompatibility Complexes Are Targeted in Autoimmune Diabetes in Mice  

PubMed Central

OBJECTIVE—Weak major histocompatibility complex (MHC) binding of self-peptides has been proposed as a mechanism that may contribute to autoimmunity by allowing for escape of autoreactive T-cells from the thymus. We examined the relationship between the MHC-binding characteristics of a ?-cell antigen epitope and T-cell autoreactivity in a model of autoimmune diabetes. RESEARCH DESIGN AND METHODS—The binding of a proinsulin epitope, proinsulin-1(47–64) (PI-1[47–64]), to the MHC class II molecules I-Ag7 and I-Ak was measured using purified class II molecules. T-cell reactivity to the proinsulin epitope was examined in I-Ag7+ and I-Ak+ mice. RESULTS—C-peptide epitopes bound very weakly to I-Ag7 molecules. However, C-peptide–reactive T-cells were induced after immunization in I-Ag7–bearing mice (NOD and B6.g7) but not in I-Ak–bearing mice (B10.BR and NOD.h4). T-cells reactive with the PI-1(47–64) peptide were found spontaneously in the peripancreatic lymph nodes of pre-diabetic NOD mice. These T-cells were activated by freshly isolated ?-cells in the presence of antigen-presenting cells and caused diabetes when transferred into NOD.scid mice. CONCLUSIONS—These data demonstrate an inverse relationship between self-peptide–MHC binding and T-cell autoreactivity for the PI-1(47–64) epitope in autoimmune diabetes.

Levisetti, Matteo G.; Lewis, Danna M.; Suri, Anish; Unanue, Emil R.

2008-01-01

377

? Cells cannot directly prime diabetogenic CD8 T cells in nonobese diabetic mice  

PubMed Central

Type 1 diabetes (T1D) is caused by the destruction of insulin-producing islet ? cells. CD8 T cells are prevalent in the islets of T1D patients and are the major effectors of ? cell destruction in nonobese diabetic (NOD) mice. In addition to their critical involvement in the late stages of diabetes, CD8 T cells are implicated in the initiation of disease. NOD mice, in which the ?2-microglobulin gene has been inactivated by gene targeting (NOD.?2M?/?), have a deficiency in CD8 T cells and do not develop insulitis, which suggests that CD8 T cells are required for the initiation of T1D. However, neither in humans nor in NOD mice have the immunological requirements for diabetogenic CD8 T cells been precisely defined. In particular, it is not known in which cell type MHC class I expression is required for recruitment and activation of CD8 T cells. Here we have generated transgenic NOD mice, which lack MHC class I on mature professional antigen-presenting cells (pAPCs). These “class I APC-bald” mice developed periislet insulitis but not invasive intraislet insulitis, and they never became diabetic. Recruitment to the islet milieu does not therefore require cognate interaction between CD8 T cells and MHC class I on mature pAPCs. Conversely, such an interaction is critically essential to allow the crucial shift from periislet insulitis to invasive insulitis. Importantly, our findings demonstrate unequivocally that CD8 T cells cannot be primed to become diabetogenic by islet ? cells alone.

de Jersey, James; Snelgrove, Sarah L.; Palmer, Stephanie E.; Teteris, Simon A.; Mullbacher, Arno; Miller, Jacques F. A. P.; Slattery, Robyn M.

2007-01-01

378

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

379

Cellular Action of Vasopressin in Medullary Tubules of Mice with Hereditary Nephrogenic Diabetes Insipidus  

PubMed Central

Our previous studies (1974. J. Clin. Invest.54: 753-762.) suggested that impaired metabolism of cyclic AMP (cAMP) may be involved in the renal unresponsiveness to vasopressin (VP) in mice with hereditary nephrogenic diabetes insipidus (NDI). To localize such a defect to specific segments of the nephron, we studied the activities of VP-sensitive adenylate cyclase, cAMP phosphodiesterase (cAMP-PDIE), as well as accumulation of cAMP in medullary collecting tubules (MCT) and in medullary thick ascending limbs of Henle's loop (MAL) microdissected from control mice with normal concentrating ability and from mice with hereditary NDI. Adenylate cyclase activity stimulated by VP or by NaF was only slightly lower (?24%) in MCT from NDI mice, compared with controls. In MAL of NDI mice, basal, VP-sensitive, and NaF-sensitive adenylate cyclase was markedly (> ?60%) lower compared with MAL of controls. The specific activity of cAMP-PDIE was markedly higher in MCT of NDI mice compared with controls, but was not different between MAL of control and NDI mice. Under present in vitro conditions, incubation of intact MCT from control mice with VP caused a striking increase in cAMP levels (>10), but VP failed to elicit a change in cAMP levels in MCT from NDI mice. When the cAMP-PDIE inhibitor 1-methyl-3-isobutyl xanthine (MIX) was added to the above incubation, VP caused a significant increase in cAMP levels in MCT from both NDI mice and control mice. Under all tested conditions, cAMP levels in MCT of NDI mice were lower than corresponding values in control MCT. Under the present experimental setting, VP and other stimulating factors (MIX, cholera toxin) did not change cAMP levels in MAL from either control mice or from NDI mice. The results of the present in vitro experiments suggest that the functional unresponsiveness of NDI mice to VP is perhaps mainly the result of the inability of collecting tubules to increase intracellular cAMP levels in response to VP. In turn, this inability to increase cAMP in response to VP is at least partly the result of abnormally high activity of cAMP-PDIE, a somewhat lower activity of VP-sensitive adenylate cyclase in MCT of NDI mice, and perhaps to a deficiency of some other as yet unidentified factors. The possible contribution of low VP-sensitive adenylate cyclase activity in MAL of NDI mice to the renal resistance to VP remains to be defined.

Jackson, Brian A.; Edwards, Richard M.; Valtin, Heinz; Dousa, Thomas P.

1980-01-01

380

Effect of single dose administration of diuretics on the blood sugar of alloxan-diabetic mice or mice made hyperglycaemic by the acute administration of diazoxide  

PubMed Central

1. Frusemide produced hyperglycaemia in mice when administered together with diazoxide. The interaction between the drugs in elevating the blood sugar was shown to be additive. 2. The diuretic, natriuretic and kaliuretic effects of frusemide were very markedly attenuated by diazoxide. 3. Neither ethacrynic acid nor hydrochlorothiazide exerted any effect upon blood sugar when administered together with diazoxide. 4. Bilateral nephrectomy completely prevented the hyperglycaemic effect of frusemide in normal mice and in mice treated with diazoxide. Diazoxide itself still produced hyperglycaemia in nephrectomized mice. 5. Frusemide, ethacrynic acid and diazoxide, but not hydrochlorothiazide, each produced hyperglycaemia in alloxan-diabetic mice, this being prevented by bilateral nephrectomy.

Foy, J. M.; Furman, B. L.

1973-01-01

381

Leptin transgene expression in the hypothalamus enforces euglycemia in diabetic, insulin-deficient nonobese Akita mice and leptin-deficient obese ob\\/ ob mice  

Microsoft Academic Search

We have tested the hypothesis that sustained leptin action in the hypothalamus alone can engender and maintain euglycemia in wild type mice and in two monogenic diabetic models, the insulin-deficient nonobese Akita mice and the hyperinsulinemic leptin-deficient obese, ob\\/ob mice. A single intracerebroventricular injection of recombinant adeno-associated virus vector encoding leptin (rAAV-lep) enhanced leptin transgene expression in the hypothalamus without

Naohiko Ueno; Akio Inui; Pushpa S. Kalra; Satya P. Kalra

2006-01-01

382

Altered pathogenesis in encephalomyocarditis virus (D variant)-infected diabetes-susceptible and resistant strains of mice  

Microsoft Academic Search

Summary  The D variant of encephalomyocarditis virus (EMCV-D) induces a diabetes mellitus-like disease in male SJL\\/J mice. Other inbred strains, while resistant to the diabetogenic effect, exhibit strikingly different responses to this virus. In these studies, infection of diabetes resistant C3H mice with the D variant produces massive acute pancreatitis with little apparent direct islet cell involvement. This exocrine tropism is

K. L. Gaines; S. G. Kayes; G. L. Wilson

1986-01-01

383

Antihyperglycemic, antihyperlipidemic and antioxidant activities of polysaccharides from Catathelasma ventricosum in streptozotocin-induced diabetic mice.  

PubMed

It is the first time to extract polysaccharides (CVPs) from Catathelasma ventricosum. The antihyperglycemic and antioxidant activity of CVPs in streptozotocin-induced diabetic mice were examined. Compared with untreated diabetic mice, the administration of CVPs for 30 days caused a significant decrease in the concentrations of blood glucose, total cholesterol (TC), triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C) and maleic dialdehyde (MDA), and a significant increase in the concentrations of high density lipoprotein-cholesterol (HDL-C) and the activities of antioxidant enzymes. Specially, when normal mice were treated with CVPs, all detection indexes and pathologic morphologies of liver, kidney and pancreas are similar to untreated normal mice, which indicated CVPs are safe for normal mice. In addition, the average molecular weight of CVPs was estimated to be from 3.7 × 10(3) to 1.7 × 10(7)Da and they were mainly composed of glucose (93.5%) with the conformation of ?-d-Glucopyranose. PMID:23500773

Liu, Yuntao; Sun, Jun; Rao, Shengqi; Su, Yujie; Yang, Yanjun

2013-03-14

384

Glycemic control with insulin prevents progression of dental caries and caries-related periodontitis in diabetic WBN/KobSlc rats.  

PubMed

We have previously reported that dental caries progress in spontaneously and chemically induced diabetic rodent models. The aim of this study was to clarify the relationship between hyperglycemia and dental caries by evaluating the preventive effect of glycemic control with insulin on the progression of the lesions in diabetic rats. Male WBN/KobSlc rats aged 15 weeks were divided into groups of spontaneously diabetic rats (intact group), spontaneously diabetic rats with insulin treatment (INS group), alloxan-induced prolonged diabetic rats (AL group), and alloxan-induced prolonged diabetic rats with insulin treatment (AL + INS group). The animals were killed at 90 weeks of age, and their oral tissue was examined. Dental caries and periodontitis were frequently detected in the intact group, and the lesions were enhanced in the AL group (in which there was an increased duration of diabetes). Meanwhile, glycemic control with insulin reduced the incidence and severity of dental caries and periodontitis in the INS group, and the effects became more pronounced in the AL + INS group. In conclusion, glycemic control by insulin prevented the progression of dental caries and caries-related periodontitis in the diabetic rats. PMID:23076036

Nakahara, Yutaka; Sano, Tomoya; Kodama, Yasushi; Ozaki, Kiyokazu; Matsuura, Tetsuro

2012-10-17

385

BCG Vaccination Prevents Insulin-Dependent Diabetes Mellitus (IDDM) in NOD Mice after Disease Acceleration with Cyclophosphamide  

Microsoft Academic Search

We have previously shown that immunotherapy with complete Freund's adjuvant (CFA) or BCG is highly effective in the prevention of spontaneous insulin-dependent diabetes mellitus (IDDM) and in circumventing the rejection of syngeneic islet grafts in diabetic NOD mice. This protection is reversed by treatment with cyclophosphamide (Cy). The present study was undertaken to determine the effect of BCG vaccination on

Hui-Yu Qin; Bhagirath Singh

1997-01-01

386

Cytokine Responses of Splenocytes of Female and Male Non-Obese Diabetic Mice Induced by Lactic Acid Bacteria  

Microsoft Academic Search

\\u000a It has been well recognized that the incidences of autoimmune diseases such as insulin-dependent diabetes mellitus (IDDM)\\u000a and rheumatoid arthritis (RA) are largely influenced by genetic factors [1, 2]. For example, non-obese diabetic (NOD) mice,\\u000a an animal model for spontaneous IDDM, show a clear female predilection [3].

Atsushi Enomoto; Mohd Azraai Bin Jamal; Hiromi Mitsui; Hiromi Kimoto-Nira; Chise Suzuki; Koko Mizumachi

387

Dose dependent development of diabetes mellitus and non-alcoholic steatohepatitis in monosodium glutamate-induced obese mice  

Microsoft Academic Search

AimsWe have recently reported that monosodium glutamate (MSG) induces severe obesity with diabetes mellitus and\\/or non-alcoholic fatty liver disease (NAFLD)\\/non-alcoholic steatohepatitis (NASH) in Crj:CD-1(ICR) neonatal mice. In this study, we investigated the effects of varying the dose of MSG on the resulting obesity and diabetes mellitus.

Yoshiyuki Sasaki; Wataru Suzuki; Tsutomu Shimada; Seiichi Iizuka; Satoko Nakamura; Mitsunobu Nagata; Makoto Fujimoto; Koichi Tsuneyama; Ryoji Hokao; Ken-ichi Miyamoto; Masaki Aburada

2009-01-01

388

Elimination of insulitis and augmentation of islet ? cell regeneration via induction of chimerism in overtly diabetic NOD mice  

PubMed Central

Type 1 diabetes in both humans and nonobese diabetic (NOD) mice results from autoreactive T cell destruction of insulin-producing ? cells. Cure of type 1 diabetes may require both reversal of autoimmunity and regeneration of ? cells. Induction of chimerism via allogeneic hematopoietic cell transplantation has been shown to reestablish tolerance in both prediabetic and diabetic NOD mice. However, it is unclear whether this therapy augments ? cell regeneration. Furthermore, this procedure usually requires total body irradiation conditioning of recipients. The toxicity of total body irradiation conditioning and potential for graft-versus-host disease (GVHD) limit the application of allogeneic hematopoietic cell transplantation for treating type 1 diabetes. Here we report that injection of donor bone marrow and CD4+ T cell-depleted spleen cells induced chimerism without causing GVHD in overtly diabetic NOD mice conditioned with anti-CD3/CD8 and that induction of chimerism in new-onset diabetic NOD mice led to elimination of insulitis, regeneration of host ? cells, and reversal of hyperglycemia. Therefore, this radiation-free GVHD preventive approach for induction of chimerism may represent a viable means for reversing type 1 diabetes.

Zhang, Chunyan; Todorov, Ivan; Lin, Chia-Lei; Atkinson, Mark; Kandeel, Fouad; Forman, Stephen; Zeng, Defu

2007-01-01

389

Tissue-targeted therapy of autoimmune diabetes using dendritic cells transduced to express IL-4 in NOD mice  

PubMed Central

A deficit in IL-4 production has been previously reported in both diabetic human patients and non-obese diabetic (NOD) mice. In addition, re-introducing IL-4 into NOD mice systemically, or as a transgene, led to a beneficial outcome in most studies. Here, we show that prediabetic, 12-wk old female NOD mice have a deficit in IL-4 expression in the pancreatic lymph nodes (PLN) compared to age-matched diabetes-resistant NOD.B10 mice. By bioluminescence imaging, we demonstrated that the PLN was preferentially targeted by bone marrow-derived dendritic cells (DCs) following intravenous (IV) administration. Following IV injection of DCs transduced to express IL-4 (DC/IL-4) into 12-wk old NOD mice, it was possible to significantly delay or prevent the onset of hyperglycemia. We then focused on the PLN to monitor, by microarray analysis, changes in gene expression induced by DC/IL-4 and observed a rapid normalization of the expression of many genes, that were otherwise under-expressed compared to NOD.B10 PLN. The protective effect of DC/IL-4 required both MHC and IL-4 expression by the DCs. Thus, adoptive cellular therapy, using DCs modified to express IL-4, offers an effective, tissue-targeted cellular therapy to prevent diabetes in NOD mice at an advanced stage of pre-diabetes, and may offer a safe approach to consider for treatment of high risk human pre-diabetic patients.

Creusot, Remi J; Yaghoubi, Shahriar S; Kodama, Keiichi; Dang, Demi N; Dang, Vu H; Breckpot, Karine; Thielemans, Kris; Gambhir, Sam S; Fathman., C Garrison

2008-01-01

390

Bis(quercetinato)oxovanadium IV Reverses Metabolic Changes in Streptozotocin-Induced Diabetic Mice  

PubMed Central

Organic vanadium compounds offer several advantages in the treatment of diabetes, yet they are impractical to use because of known side effects. In order to ameliorate the side effects of vanadium, we conjugated it with quercetin to form bis(quercetinato)oxovanadium IV (BQOV). This study evaluates the effect of BQOV treatment on carbohydrate metabolism and overall oxidative stress in streptozotocin-induced (STZ) diabetic mice. Administration of BQOV orally to diabetic mice for 3 weeks led to a reduction of blood glucose levels and the animals exhibited normal glucose tolerance at the end of the study period. The increase in glucose uptake by skeletal muscle and liver as well as the normalization of mRNA levels of G-6-Pase and glucokinase in the liver after BQOV treatment pointed to improvements in carbohydrate metabolism. The analysis of the antioxidant status of serum, liver and pancreas revealed reduced oxidative stress in BQOV-treated animals compared to untreated diabetic controls. Serum analyses for kidney and liver function showed that BQOV treatment provoked total protection of the kidney and partial protection of the liver from diabetogenic insults. The number of insulin-positive cells and the amount of pancreatic insulin in treated mice (1.2038 ± 0.34 ng/mg tissue) did not account for pancreatic regeneration but suggested an insulin-mimetic action on the part of BQOV. Moreover, administration of BQOV for 3 weeks did not show any visible side-effects. This data indicate that BQOV is a safe and potent agent for diabetes treatment, because it is able to improve carbohydrate metabolism and to reduce overall oxidative stress.

Shukla, Ruchi; Padhye, Subhash; Modak, Manisha; Ghaskadbi, Saroj S.; Bhonde, Ramesh R.

2007-01-01

391

Angiopoietin-1 gene transfer improves impaired wound healing in genetically diabetic mice without increasing VEGF expression.  

PubMed

Ang-1 (angiopoietin-1) improves the ineffective angiogenesis and impaired wound healing in diabetes; however, the mechanism underlying this positive effect is still far from being completely understood. In the present study, we investigated whether rAAV (recombinant adeno-associated virus)-Ang-1 gene transfer could improve wound repair in genetically diabetic mice (db+/db+) and the mechanism(s) by which it causes new vessel formation. An incisional skin-wound model in diabetic and normoglycaemic mice was used. After the incision, animals received rAAV-LacZ or rAAV-Ang-1 in the wound edge. After 7 and 14 days, wounds were used to (i) confirm Ang-1 gene transfer, (ii) assess histologically the healing process, (iii) evaluate wound-breaking strength, and (iv) study new vessel formation by PECAM-1 (platelet/endothelial cell adhesion molecule-1) immunostaining. Finally, we investigated VEGF (vascular endothelial growth factor) mRNA and protein levels, eNOS (endothelial NO synthase) expression and VEGFR-1 and VEGFR-2 (VEGF receptor-1 and -2 respectively) immunostaining. The efficiency of Ang-1 gene transfer was confirmed by increased mRNA and protein expression of the protein. rAAV-Ang-1 significantly improved the healing process, stimulating re-epithelization and collagen maturation, increasing breaking strength and significantly augmenting the number of new vessels, as indicated by PECAM-1 immunostaining. However, Ang-1 gene transfer did not modify the decrease in VEGF mRNA and protein expression in diabetic mice; in contrast, Ang-1 increased eNOS expression and augmented nitrate wound content and VEGFR-2 immunostaining and protein expression. Ang-1 gene transfer did not change vascular permeability. Similar results were obtained in normoglycaemic animals. In conclusion, our results provide strong evidence that Ang-1 gene transfer improves the delayed wound repair in diabetes by inducing angiogenesis in a VEGF-independent manner. PMID:18078386

Bitto, Alessandra; Minutoli, Letteria; Galeano, Maria Rosaria; Altavilla, Domenica; Polito, Francesca; Fiumara, Tiziana; Calò, Margherita; Lo Cascio, Patrizia; Zentilin, Lorena; Giacca, Mauro; Squadrito, Francesco

2008-06-01

392

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, Di