The Related Study On Leptin, Fatty Acids And Pancreatic Islets' Function

In order to reveal the effect of fatty acids which cause pancreatic islets' lipid-apoptosis and the effect of leptin which antagonizes apoptosis and regulates thermogenesis, we investigated the effects of leptin and free fatty acids on NO, intracellular triglyceride content, the expression of UCP-2mRNA and iNOSmRNA of rat pancreatic islets. The results will provide an objective evidence for obesity's pathogeny research and treatment, diabetic complication's prevention.Methods:1.After rat pancreatic islets were extracted , they were cultured by leptin and fatty acids . Then they were randomly divided to four groups: group leptin, group FA, group leptin+FA and controls.2. To value the effect of leptin and fatty acids on pancreatic islets' lipid-apoptosis, we measured intracellular triglyceride content, NO and the expression of iNOSmRNA.3. To evaluate the effect of leptin and fatty acids on pancreatic islets' function and to try to explain the internal relationship between UCP-2 gene and insulin sec 'etion, we measured the expression of UCP-2mRNA and the level of insulin secretion.Results:1. Compared with controls, TG content increased in group FA. It reduced in groupleptin+FA but couldn't attain the level in controls.2. Compared with controls, NO and the expression of iNOSmRNA increased in group FA. They reduced in group leptin+FA but couldn't attain the level in controls.3.Compared with controls, the expression of UCP-2mRNA was upregulated in group FA and group leptin+FA.4.Compared with controls, both basal insulin secretion and GSIS reduced in group FA. Basal insulin secretion increased in group leptin and GSIS level was higher than basal insulin secretion but lower than controls. Conclusions:1. 20ng/ml leptin and ImM FA can simulate the level of leptin and plasma fatty acid in obesity individual.2. FA can increase intracellular TG content of pancreatic islets and cause FA overload. Leptin reduces its content, so leptin regulates fatty acids homeostasis.3. FA can increase NO and the expression of iNOSmRNA of pancreatic islets. It is possible that FA is a factor which causes lipid-apoptosis of pancreatic islets. Leptin can reduce NO and the expression of UCP-2mRNA. It is possible that leptin may counteract lipid-apoptosis.4. FA and leptin can up regulate the expression of UCP-2mRNA. It explains leptin can regulate thermogenesis by extraneural path and FA impairs islets' function by changing the expression of this gene.5. FA can reduce insulin secretion and impair islets' function. Leptin acts directly on pancreatic islets and stimulates basal insulin secretion and it may be one of the reason of hyperinsulinemia. The mechanism of effect of leptin on GSIS can't be clearly explained .