Potentiation of glucagon-like peptide 1 insulinotropic action by succinic acid dimethyl ester

The glucagon-like peptide 1 (7-36) amide (GLP-1, 1.0 nM) was administered to isolated rat pancreases perfused either in the absence of exogenous nutrient or presence of 10 mM succinic acid dimethyl ester (SAD). In the absence of any exogenous nutrient, GLP-1 failed to affect either insulin or glucagon release. The administration of SAD caused a biphasic stimulation of insulin output and inhibited glucagon secretion. In the presence of SAD, GLP-1 still failed to affect glucagon release, but markedly enhanced insulin secretion. These findings indicate that GLP-1 is not truly a glucose-dependent, but rather nutrient-dependent insulin secretagogue. They also suggest that non-glucidic nutrients, such as SAD, could be used to optimalize the B-cell secretory response to GLP-1 in non-insulin-dependent diabetes mellitus.