Rosiglitazone inhibits hepatic insulin resistance induced by chronic pancreatitis and IKK-β/NF-κB expression in liver

摘要

Objectives: This study aimed to investigate the influence of rosiglitazone on hepatic insulin resistance and the expressions of IκB kinase-β (IKK-β)uclear factor-κB (NF-κB) in chronic pancreatitis (CP).Methods: After CP was induced in rats, rosiglitazone and GW9662 were administered at the doses of 4 and 2 mg/kg per day for 4 weeks, respectively. Then, glucose and insulin tolerance tests were performed Hepatocytes were isolated for the glucose release experiments. Determination of the IKK-β, NF-κB, and Ser307p-insulin receptor substrates-1 (Ser307p-IRS-1) expression in the liver was performed.Results: The increased plasma glucose, reduced insulin sensitivity, and the capacity of insulin to suppress glucose release in hepatocytes were observed in CP rats. The IKK-β, NF-Kβ, and Ser307p-IRS-1 expressions were significantly higher in the liver of CP rats than in sham-operated rats (P < 0.05). Rosiglitazone treatment significantly improved hepatic insulin sensitivity and inhibited the IKK-β, NF-κB, and Ser307p-IRS-1 expressions in the liver (P < 0.05). Counteraction with peroxisome proliferator-activated receptor-γ by GW9662 attenuated the aforementioned effects of rosiglitazone.Conclusions: Rosiglitazone attenuates hepatic insulin resistance induced by CP. The inhibition of hepatic IKK-β and NF-κβ expressions via peroxisome proliferator-activated receptor-γ may be involved in the therapeutic effect of rosiglitazone.