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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

Department of Pharmacology, Cardiovascular and Diabetes Research Laboratory, All India Institute of Medical Sciences, New Delhi, India.
The British journal of nutrition (Impact Factor: 3.34). 06/2011; 106(11):1713-23. DOI: 10.1017/S000711451100225X
Source: PubMed

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.

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    • "e of ethanol - related behaviors , lead to an important conclusion , namely , that the changes in the voluntary ethanol intake and CPP scores of mice induced by naringin were dependent on PPAR - g activation . This is consistent with previous reports which showed that GW9662 significantly reverse the activities of the PPAR - g agonist , naringin ( Sharma et al . , 2011 ) ."
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    • "and 81.51–98.1 mg/100 g fresh weight, respectively) (Yoo et al., 2004). Hesperidin and naringin attenuated hyperlipidaemia and hepatic steatosis, partly by regulating fatty acid and cholesterol metabolism through enhancing hepatic and adipocyte PPARγ expression in type-2 diabetic animals (Jung, Lee, Park, Kang, & Choi, 2006; Sharma et al., 2011). In this study, administration of yuzu peel increased the mRNA expression of markers of lipid oxidation (pparab and acadm in liver, pparg in adipose tissue, and acox1 in both) and mature adipocytes (adipoqb in adipose tissue) in DIO zebrafish without affecting markers of lipogenesis (fasn and acacb in adipose tissue and liver) (Figs 3 and 4). "
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