TY - JOUR
T1 - 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
AU - Sharma, Ashok Kumar
AU - Bharti, Saurabh
AU - Ojha, Shreesh
AU - Bhatia, Jagriti
AU - Kumar, Narender
AU - Ray, Ruma
AU - Kumari, Santosh
AU - Arya, Dharamvir Singh
PY - 2011/12/14
Y1 - 2011/12/14
N2 - 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.
AB - 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.
KW - Heat shock proteins
KW - Insulin resistance
KW - Naringin
KW - PPARγ
KW - Type 2 diabetes
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U2 - 10.1017/S000711451100225X
DO - 10.1017/S000711451100225X
M3 - Article
C2 - 21736771
AN - SCOPUS:82255195245
SN - 0007-1145
VL - 106
SP - 1713
EP - 1723
JO - British Journal of Nutrition
JF - British Journal of Nutrition
IS - 11
ER -