Hexose metabolism in pancreatic islets: Apparent dissociation between the secretory and metabolic effects of D-fructose

In rat pancreatic islets, D-fructose causes a concentration-related shift to the left of the sigmoidal relationship between insulin release and D-glucose concentration. For instance, when D-fructose is tested at a 80 mM concentration, which is close to the threshold value for stimulation of insulin release by the ketohexose in the absence of D-glucose, a close-to-maximal secretory response is recorded in islets concomitantly exposed to as little as 6.0 to 8.3 mM D-glucose. Under these conditions, however, D-fructose fails to affect the utilization of D-[5-H-3]glucose, the oxidation of D-[U-C-14]glucose, or its conversion to either C-14-labeled acidic metabolites or amino acids. Under the same experimental conditions, the oxidation of D-[U-C-14]fructose and its conversion to C-14-labeled amino acids represent no more than 80-85% of the corresponding values found with 6 mM D-[U-C-14]glucose. Actually, the total output of (CO2)-C-14 attributable to the oxidation of both D-[U-C-14]glucose (6 mM) and D-[U-C-14]fructose (80 mM) remains lower than that found in the sole presence of 8.3 mM D-[U-C-14]glucose, despite the much higher rate of insulin secretion found in the former compared to the latter situation. These findings suggest that the insulinotropic action of D-fructose cannot be fully accounted for by its capacity to act as a fuel in islet cells, as hit were to involve the generation of a second messenger distinct from those coupling factors currently implied in the process of nutrient-stimulated insulin release. (C) 1996 Academic Press, Inc.