Hexose metabolism in pancreatic islets. Metabolic and secretory responses to D-fructose

D-Fructose (3.3 to 33.0 mmol/liter) caused a concentration-related increase in insulin output from rat islets exposed to D-glucose (3.3 to 7.0 mmol/liter), such an increase not being more marked in mouse islets. The fructose-induced increment in insulin release, relative to that evoked by D-glucose, was two times higher in islets exposed to D-glucose than in islets stimulated by D-mannose, 2-ketoisocaproate, or nonnutrient secretagogs. Likewise, the metabolism of D-fructose in islet cells was significantly different in the absence or presence of D-glucose. Thus, the ketose was largely channeled into the pentose phosphate pathway in glucose-deprived, but not so in glucose-stimulated, islets. In both glucose-deprived and glucose-stimulated islets, however, the magnitude of the secretory response to D-fructose was commensurate with the increase in ATP production attributable to its catabolism. These findings indicate that the metabolic fate of hexoses--and, hence, their insulinotropic capacity--is not ruled solely at the level of their phosphorylation.