Insulin Biosynthesis and Secretion — A Still Unsettled Topic

Abstract

The mechanism of insulin biosynthesis and secretion is only partially understood, and new evidence suggests that its complexity is greater than previously thought. Thus, ultrastructural evidence indicates the presence of a discontinuous, microvesicular transfer of secretory material between rough endoplasmic reticulum and Golgi complex, and further suggests that more than one morphologic mode of insulin release must be considered. Similarly, biochemical evidence suggests that stimulation of insulin release involves a multicomponent system including cyclic 3′, 5′ AMP, α and β autonomous nervous receptors, Ca⁺⁺ and at least two types of substrate effects, one of them specific for certain substrates only. The complexity of the stimulatory mechanism involved is particularly well illustrated by studies with metabolic inhibitors — for example, mannoheptulose inhibits glucose-induced stimulation of insulin release, as expected, but enhances insulin release induced by tolbutamide. D-2-deoxyglucose inhibits glucose-induced but enhances pyruvate-induced or tolbutamide-induced release of the hormone.