Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats

Pankaj K. Bagul, Harish Middela, Saidulu Matapally, Raju Padiya, Tanmay Bastia, K. Madhusudana, B. Raghunath Reddy, Sumana Chakravarty, Sanjay K. Banerjee

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130 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)260-268
Number of pages9
JournalPharmacological Research
Volume66
Issue number3
DOIs
StatePublished - Sep 2012

Bibliographical note

Funding Information:
Financial support was provided by Ramalingaswami fellowship funds to SKB and SC from Department of Biotechnology (DBT), Govt. of India and in part, IICT institute fund . SKB has grant support from DBT ( SR/SO/HS-110/2008 ). PKB is a Senior Research Fellow from Council of Scientific and Industrial Research (CSIR). We wish to thank Kumar organic products Ltd., Bangalore for providing gift sample of Resveratrol. We wish to thank Dr. K. Praveen Kumar for his excellent technical assistance and Dr. J. S. Yadav, Director, IICT, Hyderabad for providing all kind of support for this work. We would like to gratefully acknowledge Dr. Mohua Maulik for her suggestions and critical review of the manuscript.

Keywords

  • Metabolic syndrome
  • Metformin
  • NRF2
  • Oxidative stress
  • Resveratrol
  • Type-2 diabetes

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