title: Sirtuin 1 and 7 mediate resveratrol-induced recovery from hyper-anxiety in high-fructose-fed prediabetic rats.
abstract: Hyperglycaemia in diabetes is either caused by reduced availability of insulin (type 1 diabetes, T1D) or insulin resistance to the cells (type 2 diabetes, T2D). In recent years, the prevalence of T2D has increased to an alarming proportion, encompassing 95 percent of the total diabetic burden, probably due to economy-driven changes in lifestyle. Recent epidemiological studies show comorbid depression, anxiety and related mental illness. To explore the molecular mechanisms underlying this comorbid conditions, we used Sprague-Dawley rats on high-fructose diet for 8 weeks to induce prediabetic condition. Rats with this metabolic syndrome also showed hyper-anxiety when they were subjected to anxiety-related behavioural assays. Rats were administered with resveratrol, an activator of sirtuins, and metformin, a standard antidiabetic drug, simultaneously with fructose. We observed that resveratrol was more effective in protecting from both the metabolic (prediabetic) and affective (anxiety) disorders than metformin. Molecular studies showed that recovery was associated with the upregulation of few nuclear sirtuins that act epigenetically - Sirt 1 and 7, which were significantly attenuated in the striatum of prediabetic rats. In conclusion, our study showed that hyper-anxiety associated with prediabetic condition is ameliorated by resveratrol through modulation of sirtuins, which is more or less similar to metformin.
authors: Chemical Biology, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India.
authors: B Raghunath
authors: BR
authors: Reddy
authors: Swati
authors: S
authors: Maitra
authors: Priya
authors: P
authors: Jhelum
authors: K Praveen
authors: KP
authors: Kumar
authors: Pankaj K
authors: PK
authors: Bagul
authors: Gagandeep
authors: G
authors: Kaur
authors: Sanjay K
authors: SK
authors: Banerjee
authors: Arvind
authors: A
authors: Kumar
authors: Sumana
authors: S
authors: Chakravarty
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001008:Anxiety Disorders / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000473:pathology; D004032:Diet / Q000009:adverse effects; D044127:Epigenesis, Genetic / Q000235:genetics; D005632:Fructose / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D008687:Metformin / Q000008:administration & dosage; D011236:Prediabetic State / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D051381:Rats; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000096:biosynthesis / Q000235:genetics*; D037761:Sirtuins / Q000096:biosynthesis / Q000235:genetics*; D013267:Stilbenes / Q000008:administration & dosage
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; C510661:SIRT7 protein, human; D013267:Stilbenes; D005632:Fructose; D008687:Metformin; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D000077185:Resveratrol