The stimulus-secretion coupling of glucose-induced insulin release: fuel metabolism in islets deprived of exogenous nutrient.

The fuel hypothesis for insulin release postulates that the secretory response to nutrient secretagogues reflects their capacity to augment catabolic fluxes in pancreatic islet cells. Hence, both the oxidation of exogenous nutrients and their effect upon the metabolism of endogenous nutrients should be taken into consideration to account for the stimulation of insulin release. In the present work, an attempt was made to quantify the respective contribution of carbohydrates, fatty acids, and amino acids in the respiration of islets deprived of exogenous nutrient. The metabolism of glycerol, fatty acids, and amino acids was found to account for the major part of the basal respiratory rate. Glucose modestly decreased the oxidation of endogenous fatty acids, lowered the production of NH4+, but did not impair the oxidative catabolism of 2-keto acids derived from endogenous amino acids. These findings suggest that the catabolism of noncarbohydrate nutrients largely contributes to the respiration of the islets, even when the latter are exposed to circulating glucose in its physiological concentration.