Potentiation of GLP-1 insulinotropic action by a nonglucidic nutrient in the pancreas of diabetic GK rats.

Glucagon-like peptide 1 (GLP-1) is often referred to as a glucose-dependent insulinotropic agent and is currently under investigation as a tool in the treatment of noninsulin-dependent diabetes. This report shows that, in the absence of glucose, a nonglucidic nutrient, namely succinic acid dimethyl ester (SAD), allows full expression of the insulinotropic potential of GLP-1 in the perfused pancreas from diabetic GK rats. Thus, whereas the insulin and glucagon responses to GLP-1 in GK rats differ from those previously documented in nondiabetic animals when tested in the absence of exogenous nutrient, the secretory response of the endocrine pancreas to GLP-1 is virtually normalized in the GK rats when SAD is incorporated into the perfusate. It is proposed, therefore, that nonglucidic nutrients, such as SAD, may optimalize the B-cell secretory response to GLP-1 in noninsulin-dependent diabetes mellitus.