On the biochemical nature of triose- and hexose-stimulated insulin secretion

The differential effects of several specific inhibitors of intermediary metabolism, mannoheptulose, 2-deoxylucose, and iodoacetate, were studied with isolated perifused pancreatic islets stimulated with glucose, mannose, glyceraldehyde, dihydroxyacetone, or alpha-ketoisocaproate. Insulin release rates and/or capacities to metabolize these caloric stimuli served as indicators of the inhibitors' actions. Mannoheptulose and 2-deoxyglucose blocked hexose-stimulated hormone release and hexose metabolism concomitantly, but left the functional and metabolic actions of trioses unaltered. Iodoacetate blocked hexose- and triose-stimulated hormone release as well as their metabolism in a parallel fashion. The action of alpha-ketoisocaproate was not affected by any of these three inhibitory agents. The data are most easily explained by a theory that incorporates metabolic signals, arising during the degradation of insulin-releasing fuel molecules, as an integral component in the process of beta-cell stimulation.