Insulin secretion defects in liver cirrhosis can be reversed by glucagon-like peptide-1

Liver cirrhosis is often accompanied by a disturbed carbohydrate metabolism similar to type 2 diabetes. To investigate: the severity of the defect in insulin secretion in this form of diabetes, we measured insulin release fro m isolated pancreatic islets of rats with CCl4-phenobarbital-induced liver cirrhosis. Cirrhosis was confirmed by clinical signs, elevated liver enzyme s and histology. Fasting venous plasma glucose concentrations were equal in rats with liver cirrhosis and in controls. Plasma insulin and glucagon con centrations were significantly greater (P<0.01) in cirrhotic rats than in c ontrol animals. Glucose (16.7 mM)-induced stimulation of insulin release fr om pancreatic islets revealed a twofold increase in control and cirrhotic r ats. Basal and stimulated insulin secretion, however, were significantly lo wer in cirrhotic animals. The incretin hormone, glucagon-like peptide-1 (GL P-1), has therapeutic potential for the treatment of type 2 diabetes. There fore, islets from control and cirrhotic animals were incubated with GLP-1 i n concentrations from 10(-11) to 10(-6) M. GLP-1 stimulated insulin release in a concentration-dependent manner. In islets from cirrhotic rats, basal and stimulated insulin secretion was blunted compared with controls. These data show that the hyperinsulinemia observed in liver cirrhosis is not due to an increase of insulin secretion from islets, but could be explained by decreased hepatic clearance of insulin. GLP-1 may ameliorate diabetes in pa tients with liver cirrhosis.