Potentiation of the insulinotropic action of GLP-1 by succinic acid dimethyl ester in fed anaesthetized rats.

The insulinotropic action of GLP-1 is modulated by the nutritional environment of islet B-cells. This study explores whether an ester of succinic acid could be used to potentiate the insulin secretory response to GLP-1 in vivo. Fed anaesthetized male rats received a primed constant infusion (0.5 micromol followed by 0.25 micromol x min(-1) both per g body wt) of succinic acid dimethyl ester (SAD) in saline for 15 min and, at the 5th min of such an infusion, an intravenous injection of GLP-1 (5 pmol/g body wt). The ester provoked a rapid, sustained and reversible increase in plasma insulin concentration. In the SAD-infused rats, the increment in plasma insulin concentration caused by GLP-1 was more pronounced and more sustained than in saline-infused rats. It is proposed, therefore, that suitable succinic acid esters could be used to potentiate the insulinotropic action of GLP-1 in Type II (non-insulin-dependent) diabetes.