Comparison of α-ketoisocaproic acid and glucose in rats: Effects on insulin and somatostatin release and on islet camp content

Abstract The insulinotropic effects of α-ketoisocaproic acid and glucose reveal many common characteristics in vivo and in vitro. They qualify as initiators of insulin release, their action is amplified by potentiators of insulin release, and they have a similar potency at equimolar concentrations. The dynamics of insulin release evoked by α-ketoisocaproic acid and glucose are similar. Epinephrine completely inhibits the insulinotropic effect of glucose and α-ketoisocaproic acid. Mannoheptulose exhibits a complete, immediate and reversible blockade of glucoseinduced insulin release. In contrast, inhibition of α-ketoisocaproic acid-induced insulin release occurs after a lag period and is not reversed by removal of the inhibitor. α-Ketoisocaproic acid, at equimolar concentrations, is several-fold more effective than glucose in elevating cAMP content in islets. α-Ketoisocaproic acid and glucose are about equally effective in stimulating somatostatin release from isolated rat pancreatic islets. This stimulation is inhibited by epinephrine. Mannoheptulose inhibits only somatostatin release induced by glucose but not by α-ketoisocaproic acid. It is suggested that the insulinotropic characteristics of glucose and α-ketoisocaproic acid reveal many common features, while their mode of action appears to be different.