gw9662 and Pancreatitis--Chronic

This study aimed to investigate the influence of rosiglitazone on hepatic insulin resistance and the expressions of IκB kinase-β (IKK-β)/nuclear factor-κB (NF-κB) in chronic pancreatitis (CP).. 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.. 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-κB, 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.. Rosiglitazone attenuates hepatic insulin resistance induced by CP. The inhibition of hepatic IKK-β and NF-κB expressions via peroxisome proliferator-activated receptor-γ may be involved in the therapeutic effect of rosiglitazone.

Topics: Anilides; Animals; Drug Evaluation, Preclinical; Gene Expression Regulation; Glucose; Glucose Tolerance Test; Hepatocytes; I-kappa B Kinase; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Liver; Male; Pancreatitis, Chronic; PPAR gamma; Rats; Rats, Wistar; Rosiglitazone; Thiazolidinediones; Transcription Factor RelA