title: Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats.
abstract: Metabolic syndrome and oxidative stress are common complications of type 2 diabetes mellitus. The present study was designed to determine whether resveratrol, a widely used nutritional supplement, can improve insulin sensitivity, metabolic complication as well as hepatic oxidative stress in fructose-fed rats. Male Sprague Dawley rats (180-200 g) were divided into four groups with 8 animals each. Fructose-fed insulin resistant group (Dia) animals were fed 65% fructose (Research diet, USA) for a period of 8 weeks, whereas control group (Con) animals were fed 65% cornstarch (Research Diet, USA). Resveratrol, 10 mg/kg/day (Dia+Resv) or metformin 300 mg/kg/day (Dia+Met) were administered orally to the 65% fructose-fed rats for 8 weeks. At the end of the feeding schedule, Dia group had insulin resistance along with increased blood glucose, triglyceride, uric acid and nitric oxide (NO) levels. Significant (p<0.05) increase in hepatic TBARS and conjugated dienes, and significant (p<0.05) decrease in hepatic SOD and vitamin C was observed in Dia group compared to Con group. Administration of metformin or resveratrol significantly (p<0.05) normalized all the altered metabolic parameters. However, a marked insulin sensitizing action was only observed in the Dia+Resv group. Similarly, while metformin administration failed to normalize the increased TBARS levels and decreased SOD activity, resveratrol showed a more promising effect of all oxidative stress parameters measured in the present study. Attenuation of hepatic oxidative stress in fructose-fed rat liver after resveratrol administration was associated with significant (p<0.05) increase in nuclear level of NRF2 compared with other groups. The present study demonstrates that resveratrol is more effective than metformin in improving insulin sensitivity, and attenuating metabolic syndrome and hepatic oxidative stress in fructose-fed rats.
authors.affiliation: Division of Pharmacology and Chemical Biology, Indian Institute of Chemical Technology, Hyderabad 500607, India.
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Bagul
authors.forename: Harish
authors.initials: H
authors.lastname: Middela
authors.forename: Saidulu
authors.initials: S
authors.lastname: Matapally
authors.forename: Raju
authors.initials: R
authors.lastname: Padiya
authors.forename: Tanmay
authors.initials: T
authors.lastname: Bastia
authors.forename: K
authors.initials: K
authors.lastname: Madhusudana
authors.forename: B Raghunath
authors.initials: BR
authors.lastname: Reddy
authors.forename: Sumana
authors.initials: S
authors.lastname: Chakravarty
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005632:Fructose / Q000008:administration & dosage*; D005951:Glucose Tolerance Test / Q000379:methods; D005978:Glutathione / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D014527:Uric Acid / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D051267:NF-E2-Related Factor 2; D013267:Stilbenes; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D014527:Uric Acid; D005632:Fructose; D009569:Nitric Oxide; D008687:Metformin; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D001205:Ascorbic Acid; D000077185:Resveratrol