Cationic determinants of D-fructose insulinotropic action

In the absence of any other exogenous nutrient, D-fructose stimulates insul in release from rat pancreatic islets provided that it is tested at high co ncentrations in excess of a threshold value close to 80 mM, an optimal secr etory response being recorded at 240 mM. In the present study, the cationic determinants of the insulinotropic action of D-fructose, used at the latte r high concentration, were explored in perifused rat islets that had been p relabelled with either Rb-86 or Ca-45. The changes in 86Rb outflow and Ca-4 5 efflux evoked by 240 mM D-fructose were comparable to those caused by 11. 1 mM D-glucose in that both hexoses inhibited Rb-86 and Ca-45 outflow and, at normal Ca2+ concentration, caused a secondary rise in Ca-45 efflux. Thes e cationic changes coincided with stimulation of insulin release. The major differences between the two series of experiments consisted, in the islets exposed to D-fructose, in the occurrence of an early and transient increas e in Ca-45 efflux at normal extracellular Ca2+ concentration, a secondary r eascension in Rb-86 outflow and a dramatic off-response in both Rb-86 and C a-45 outflow as well as insulin release. These phenomena were also observed in islets exposed to 240 mM 3-O-methyl-D-glucose, suggesting that they may be linked to the massive influx (or efflux) of monosaccharides, as possibl y accompanied by Na+ inward co-transport, mobilization of Ca2+ from intrace llular stores and activation of voltage- and/or Ca2+-sensitive K+ channels. This interpretation was supported by the finding that, at high concentrati ons (80.0 mM) of D-glucose or D-mannose, the aldohexoses also provoked a re ascension in Rb-86 outflow and off-response in insulin release. The cationi c determinants of the insulinotropic action of D-fructose, in high concentr ation (240 mM), thus appear similar, if not identical, to those currently i ncriminated in the stimulation of insulin release by D-glucose.