Effects of inhibition of excessive insulin secretion on lipid metabolism and beta–cell functions in rats

Objective To investigate the effects of inhibition of excessive insulin secretion on lipid metabolism and beta–cell functions in high–fat feeding rats following diazoxide intervention. Methods During May 2007 and July 2008, 30 male SD rats (10–week old) were randomly divided into the normal control group (n=10; normal diet), high–fat diet group (n=10; high–fat diet), and diazoxide group (n=10; high–fat diet+ 30 mg·kg–1·d–1 diazoxide). At 8 weeks, intra–peritoneal glucose tolerance test was conducted, and serum levels of free fatty acid and triglyceride and triglyceride components in the liver or skeletal muscle were measured. Expression of ACC1 mRNA and L–CPT1 mRNA was investigated using real–time polymerase chain reaction. One–way analysis of variances and Student–Newman–Kewls test were used for data analysis. Results In intra–peritoneal glucose tolerance test, the insulin area under the curve was decreased in the high–fat diet group compared with the normal control group, while diazoxide intervention attenuated the decline (F=15.73, P<0.01). The plasma triglyceride and free fatty acid and triglyceride component in the muscles or liver were increased in the high–fat diet group, although diazoxide reversed these changes. High–fat diet alone increased the expression of ACC1 mRNA in the liver, which could be prevented by diazoxide (F=3.71, P<0.05). The expression of CPT1 mRNA in the liver or muscles was induced by high–fat diet, and diazoxide enhanced this effect (F=3.61, P<0.05; F=4.93, P<0.05). Conclusions Diazoxide may inhibit excessive insulin secretion and preserve pancreatic beta–cell function. Moreover, diazoxide could improve fatty acid metabolism and reduce fat accumulation in the liver and muscles, so as to decrease plasma levels of triglyceride and free fatty acid. Key words: Insulin; Metabolism; Beta cells; Diazoxide