The stimulus-secretion coupling of glucose-induced insulin release

The short-term influence of low concentrations of extracellular K⁺ upon insulin release was investigated in the isolated perfused rat pancreas. In the absence of glucose, the removal of extracellular K⁺ provoked a slow and transient stimulation of insulin release. This phenomenon was enhanced and prolonged at either low (2.8 mM) or high (16.7 mM) concentrations of glucose, and was abolished in the absence of extracellular Ca²⁺. Removal of extracellular K⁺ also accelerated and augmented the initial phase of glucose-induced insulin release. The late phase of glucose-induced insulin release was rapidly augmented by removal of extracellular K⁺, but inhibited in response to a partial decrease in extracellular K⁺ concentration. The release of insulin evoked by glucose in the absence of K⁺ differed from that seen in the presence of K⁺ by a progressive decline in secretory rate during prolonged stimulation, and by a lesser sensitivity towards a shortage in extracellular Ca²⁺. During constant exposure to glucose, the restoration of a normal K⁺ concentration provoked a short-lived offresponse, followed by a 8 min-period of inhibited insulin release prior to normalization of the secretory activity. These data indicate that K⁺ deprivation, apart from its long-term untoward effects upon islet function, causes a transient stimulation or facilitation of insulin release, possibly by mobilizing Ca²⁺ from intracellular stores.