In Vitro and In Vivo Insulinotropic Action of Methyl Pyruvate

Abstract

Methyl pyruvate, when tested at a 10 mM concentration, caused a rapid and sustained increase of insulin release evoked by either 7.0 or 16.7 mM D-glucose in the isolated perfused rat pancreas. Under these conditions, methyl pyruvate caused a modest and biphasic stimulation of glucagon release. In anaesthetized fed rats, methyl pyruvate (1.0 to 2.5 µmol/g body wt) given intravenously provoked a short-lived and dose-related increase in plasma insulin concentration, but failed to affect plasma glucagon concentration. D-glucose and methyl pyruvate, when injected together, acted additively upon insulin release. The in vivo secretory response to methyl pyruvate was comparable in fed, overnight fasted and 2-d starved rats, and only slightly decreased in fed animals that were injected with streptozotocin during the neonatal period. These results suggest that methyl pyruvate could be used as an insulinotropic agent to bypass site-specific defects of D-glucose metabolism in the B-cell, such as those found in starvation or non-insulin-dependent diabetes mellitus.

Key words

Methyl Pyruvate - Insulin Secretion - Perfused Pancreas