D-Glucose inhibits potassium efflux from pancreatic islet cells

Abstract

ELECTROPHYSIOLOGICAL experiments have shown that D-glucose, the major physiological stimulus of insulin release, produces depolarisation and electrical activity in pancreatic beta cells¹ and that a correlation exists between these electrical changes and the stimulation of insulin release^2–4. Continuous recordings from single beta cells have permitted characterisation of the regular burst pattern of glucose-induced electrical activity⁵; however, the ionic mechanisms underlying these electrical changes remain unclear and both active and passive ionic fluxes may be involved^6,7. Islets incubated in a medium containing a very high glucose concentration (20 mM) retain more ⁸⁶Rb⁺ than do islets incubated in the presence of 3 mM glucose; this suggests⁸ that the depolarising effects of D-glucose on beta cells might be mediated, at least in part, by a decrease in K⁺ permeability. Recent experiments further showed that tetraethylammonium, a specific blocker of K⁺ conductance, potentiated the effect of glucose on both the inhibition of ⁸⁶Rb⁺ efflux and stimulation of insulin release from isolated islets⁹. The purpose the study described here was to obtain direct evidence for an effect of glucose on potassium efflux from pancreatic islet cells and, by comparing the characteristics of this effect with the changes in insulin release and electrical activity, gain further insight into the ionic mechanisms involved in the glucose control of the secretory function of the pancreatic beta cells. It will be shown that physiological concentrations of D-glucose, but not of L-glucose, markedly modify K⁺ permeability in islet cells, that this effect requires D-glucose phosphorylation but is not the consequence of insulin release and, finally, that this change in K⁺ permeability may account for the initial depolarising effect of the sugar on beta cells.