POTENTIATION OF GLP-1 INSULINOTROPIC ACTION BY A NONGLUCIDIC NUTRIENTIN THE PANCREAS OF DIABETIC GK RATS

Glucagon-like peptide 1 (GLP-1) is often referred to as a glucose-depe ndent insulinotropic agent and is currently under investigation as a t ool in the treatment of noninsulin-dependent diabetes. This report sho ws that, in the absence of glucose, a nonglucidic nutrient, namely suc cinic acid dimethyl ester (SAD), allows full expression of the insulin otropic potential of GLP-1 in the perfused pancreas from diabetic GK r ats. Thus, whereas the insulin and glucagon responses to GLP-1 in GK r ats differ from those previously documented in nondiabetic animals whe n tested in the absence of exogenous nutrient, the secretory response of the endocrine pancreas to GLP-1 is virtually normalized in the GK r ats when SAD is incorporated into the perfusate. It is proposed, there fore, that nonglucidic nutrients, such as SAD, may optimalize the B-ce ll secretory response to GLP-1 in noninsulin-dependent diabetes mellit us. (C) 1996 Academic Press, Inc.