title: Resveratrol improves hepatic insulin signaling and reduces the inflammatory response in streptozotocin-induced diabetes.
abstract: Diabetes mellitus is a heterogeneous metabolic disorder essentially characterized by deficiency of insulin secretion, insulin receptor or post-receptor events. This study aims to investigate the effects of resveratrol administration on the metabolic characteristics, hepatic functions, histopathological features and insulin signaling pathway components in streptozotocin induced diabetes. Male Wistar rats were randomly divided into four groups: (1) control/vehicle; (2) control/20mg/kg resveratrol; (3) diabetic/vehicle; and (4) diabetic/20mg/kg resveratrol. Histopathological examinations were carried out to reveal hepatic tissue damage and inflammation. In addition to hepatic glucose, lipid, insulin, ALT, AST, resistin and XOD contents, gene and protein expressions of insulin signaling pathway components such as insulin Rβ, IRS-1, IRS-2, eNOS, PI3K, Akt, and FOXO3a were analyzed by qRT-PCR and Western blot. The rats in the diabetes group had significantly lower terminal body weight and hepatic insulin level, but significantly higher hepatic glucose, total cholesterol, triglyceride and resistin concentrations. Diabetes triggered the inflammatory process in the liver tissues that was evidenced by histopathological deformations and increase in the hepatic ALT and AST levels. Hepatic inflammation was considerably associated with insulin signaling pathway ever since a significant down-regulation of insulin signaling components; IRS-1, IRS-2, PI3K, Akt and mTOR have been identified in the diabetic group. To some extent, resveratrol treatment reversed the diabetes-induced changes in the liver tissues. Taken together, resveratrol partly improved hepatic dysfunction induced by diabetes. This may be due to the healing activity of resveratrol on insulin signaling pathway, resistin levels and hepatic glucose-lipid contents.
authors.affiliation: Department of Biology, K.Ö.Science Faculty, Karamanoglu Mehmetbey University, Karaman, Turkey. Electronic address: sadi@kmu.edu.tr.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Sadi
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey. Electronic address: mbpektas@hotmail.com.
authors.forename: Mehmet Bilgehan
authors.initials: MB
authors.lastname: Pektaş
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey. Electronic address: bugrakoca@yahoo.com.
authors.forename: Halit Bugra
authors.initials: HB
authors.lastname: Koca
authors.affiliation: Department of Histology Embryology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey. Electronic address: drmtosun@yahoo.com.
authors.forename: Murat
authors.initials: M
authors.lastname: Tosun
authors.affiliation: Department of Medical Laboratory, Ataturk Vocational School of Health Services, Afyon Kocatepe University, Afyonkarahisar, Turkey. Electronic address: tulay_akan@yahoo.com.
authors.forename: Tulay
authors.initials: T
authors.lastname: Koca
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007249:Inflammation / Q000517:prevention & control*; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D013311:Streptozocin
chemical_list: D007328:Insulin; D013267:Stilbenes; D013311:Streptozocin; D000077185:Resveratrol
keywords: Diabetes; Insulin signaling; Liver; PI3K/Akt; Resistin; Resveratrol