Synergistic insulinotropic effects of succinic acid dimethyl ester and exendin-4 in anaesthetized rats

It was recently proposed that suitable succinic acid esters could be used t o potentiate the insulinotropic action of glucagon-like peptide I (GLP-1) i n the treatment of type-2 diabetes mellitus. In such a perspective, the pre sent study aimed mainly at investigating whether exendin-4 (Ex-4), a peptid e structurally related to GLP-1(7-36)amide, and succinic acid dimethyl este r (SAD) also act synergistically upon insulin secretion in anaesthetized ra ts. Despite a higher plasma insulin concentration in SAD-infused rats (5.5 +/-1.1 ng/ml) than in saline-infused animals (1.9 +/-0.7 ng/ml), the intrav enous injection of Ex-4 augmented to a greater extent the plasma concentrat ion of insulin in the former rats (+7.4 +/-2.5 ng/ml) than in the latter an imals (+2.8 +/-0.6 ng/ml). These findings document that the insulinotropic actions of Ex-4 and GLP-1 display comparable nutrient dependency, being bot h potentiated by a non-glucidic nutrient secretagogue such as SAD.