Hexose Metabolism in Pancreatic Islets: Apparent Dissociation between the Secretory and Metabolic Effects ofD-Fructose

Abstract

In rat pancreatic islets,D-fructose causes a concentration-related shift to the left of the sigmoidal relationship between insulin release andD-glucose concentration. For instance, whenD-fructose is tested at a 80 mMconcentration, which is close to the threshold value for stimulation of insulin release by the ketohexose in the absence ofD-glucose, a close-to-maximal secretory response is recorded in islets concomitantly exposed to as little as 6.0 to 8.3 mMD-glucose. Under these conditions, however,D-fructose fails to affect the utilization ofD-[5-³H]glucose, the oxidation ofD-[U-¹⁴C]glucose, or its conversion to either¹⁴C-labeled acidic metabolites or amino acids. Under the same experimental conditions, the oxidation ofD-[U-¹⁴C]fructose and its conversion to¹⁴C-labeled amino acids represent no more than 80–85% of the corresponding values found with 6 mMD-[U-¹⁴C]glucose. Actually, the total output of¹⁴CO₂attributable to the oxidation of bothD-[U-¹⁴C]glucose (6 mM) andD-[U-¹⁴C]fructose (80 mM) remains lower than that found in the sole presence of 8.3 mMD-[U-¹⁴C]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 ofD-fructose cannot be fully accounted for by its capacity to act as a fuel in islet cells, as if it were to involve the generation of a second messenger distinct from those coupling factors currently implied in the process of nutrient-stimulated insulin release.