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

Ashok Kumar Sharma, Saurabh Bharti, Shreesh Ojha, Jagriti Bhatia, Narender Kumar, Ruma Ray, Santosh Kumari, Dharamvir Singh Arya

Research output: Contribution to journalArticlepeer-review

132 Citations (Scopus)

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 (40mg/kg, intraperitoneal (ip)) to induce type 2 diabetes. After confirmation of hyperglycaemia (>13•89mmol/l) on the 14th day, different doses of naringin (25, 50 and 100mg/kg per d) and rosiglitazone (5mg/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-ÎB 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.

Original languageEnglish
Pages (from-to)1713-1723
Number of pages11
JournalBritish Journal of Nutrition
Volume106
Issue number11
DOIs
Publication statusPublished - Dec 14 2011
Externally publishedYes

Keywords

  • Heat shock proteins
  • Insulin resistance
  • Naringin
  • PPARγ
  • Type 2 diabetes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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