Cationic determinants of D-fructose insulinotropic action.
In the absence of any other exogenous nutrient, D-fructose stimulates insulin release from rat pancreatic islets provided that it is tested at high concentrations in excess of a threshold value close to 80 mM, an optimal secretory response being recorded at 240 mM. In the present study, the cationic determinants of the insulinotropic action of D-fructose, used at the latter high concentration, were explored in perifused rat islets that had been prelabelled with either 86Rb or 45Ca. The changes in 86Rb outflow and 45Ca efflux evoked by 240 mM D-fructose were comparable to those caused by 11.1 mM D-glucose in that both hexoses inhibited 86Rb and 45Ca outflow and, at normal Ca2+ concentration, caused a secondary rise in 45Ca efflux. These 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 increase in 45Ca efflux at normal extracellular Ca2+ concentration, a secondary reascension in 86Rb outflow and a dramatic off-response in both 86Rb and 45Ca 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 possibly accompanied by Na+ inward co-transport, mobilization of Ca2+ from intracellular stores and activation of voltage- and/or Ca(2+)-sensitive K+ channels. This interpretation was supported by the finding that, at high concentrations (80.0 mM) of D-glucose or D-mannose, the aldohexoses also provoked a reascension in 86Rb outflow and off-response in insulin release. The cationic determinants of the insulinotropic action of D-fructose, in high concentration (240 mM), thus appear similar, if not identical, to those currently incriminated in the stimulation of insulin release by D-glucose.
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
H
H
Jijakli
W J
WJ
Malaisse
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008358:Mannose / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics
D002132:Calcium Radioisotopes; D007328:Insulin; D012414:Rubidium Radioisotopes; D005632:Fructose; D005947:Glucose; D008358:Mannose; D002118:Calcium