| Objective: To investigate the expression of protein tyrosine phosphatase-1B in pancreas and hypothalamus of high-fat diet-induced obesity rats. Method: After high fat diet, weight,insulin sensitive index (ISI), Triglyceride(TG), total cholesterol (TC) and fasting serum leptin were measured; Fatty degeneration in the liver was observed; Glucose tolerance test and insulin releasing test were performed; the protein expression of PTP-1B in the pancreas and hypothalamus of rats was determined with western blotting or immunohistochemical. The tyrosine phosphorylation of IRS-1 and IRβin pancreas was detected by immuno-precipitation. Results: (1) In obesity rats induced by high fat diet, the ISI was significantly decreased, fatty degeneration and leptin resisitance were observed, and glucose tolerance and the acute first-phase insulin secretary response to glucose were impaired. (2)The expression and activation of PTP-1B in the pancreas and hypothalamus of obesity rats was significantly increased. Insulin-stimulated IRβand IRS-1 tyrosine phosphorylation were reduced in the pancreas of obesity rats. Conclusion: The increased the expression and activation of PTP-1B in pancreas and hypothalamus might be an important mechanism of insulin resistance in pancreatic and leptin and insulin resistance in hypothalamus induced by high fat diet. |