IN-VITRO AND IN-VIVO INSULINOTROPIC ACTION OF METHYL PYRUVATE

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 condi tions, methyl pyruvate caused a modest and biphasic stimulation of glu cagon release. In anaesthetized fed rats, methyl pyruvate (1.0 to 2.5 mu mol/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 in jected together, acted additively upon insulin release. The in vivo se cretory response to methyl pyruvate was comparable in fed, overnight f asted and 2-d starved rats, and only slightly decreased in fed animals that were injected with streptozotocin during the neonatal period. Th ese results suggest that methyl pyruvate could be used as an insulinot ropic agent to bypass site-specific defects of D-glucose metabolism in the B-cell, such as those found in starvation or non-insulin-dependen t diabetes mellitus.