title: Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes.
abstract: Naringin, a bioflavonoid isolated from grapefruit, is well known to possess lipid-lowering and insulin-like properties. Therefore, we assessed whether naringin treatment ameliorates insulin resistance (IR), β-cell dysfunction, hepatic steatosis and kidney damage in high-fat diet (HFD)-streptozotocin (STZ)-induced type 2 diabetic rats. Wistar albino male rats were fed a HFD (55 % energy from fat and 2 % cholesterol) to develop IR and on the 10th day injected with a low dose of streptozotocin (40 mg/kg, intraperitoneal (ip)) to induce type 2 diabetes. After confirmation of hyperglycaemia (>13·89 mmol/l) on the 14th day, different doses of naringin (25, 50 and 100 mg/kg per d) and rosiglitazone (5 mg/kg per d) were administered orally for the next 28 d while being maintained on the HFD. Naringin significantly decreased IR, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, TNF-α, IL-6, C-reactive protein and concomitantly increased adiponectin and β-cell function in a dose-dependent manner. Increased thiobarbituric acid-reactive substances and decreased antioxidant enzyme activities in the serum and tissues of diabetic rats were also normalised. Moreover, naringin robustly increased PPARγ expression in liver and kidney; phosphorylated tyrosine insulin receptor substrate 1 in liver; and stress proteins heat shock protein (HSP)-27 and HSP-72 in pancreas, liver and kidney. In contrast, NF-κB expression in these tissues along with sterol regulatory element binding protein-1c and liver X receptor- expressions in liver were significantly diminished. In addition, microscopic observations validated that naringin effectively rescues β-cells, hepatocytes and kidney from HFD-STZ-mediated oxidative damage and pathological alterations. Thus, this seminal study provides cogent evidence that naringin ameliorates IR, dyslipidaemia, β-cell dysfunction, hepatic steatosis and kidney damage in type 2 diabetic rats by partly regulating oxidative stress, inflammation and dysregulated adipocytokines production through up-regulation of PPARγ, HSP-27 and HSP-72.
authors: Department of Pharmacology, Cardiovascular and Diabetes Research Laboratory, All India Institute of Medical Sciences, New Delhi, India.
authors: Ashok Kumar
authors: AK
authors: Sharma
authors: Saurabh
authors: S
authors: Bharti
authors: Shreesh
authors: S
authors: Ojha
authors: Jagriti
authors: J
authors: Bhatia
authors: Narender
authors: N
authors: Kumar
authors: Ruma
authors: R
authors: Ray
authors: Santosh
authors: S
authors: Kumari
authors: Dharamvir Singh
authors: DS
authors: Arya
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000503:physiopathology*; D044950:Flavanones / Q000494:pharmacology*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000503:physiopathology*; D008297:Male; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D044950:Flavanones; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D047495:PPAR gamma; C005274:naringin