Regulation by glucose of oscillatory electrical activity and 5-HT/insulin release from single mouse pancreatic islets in the absence of functional K-ATP channels

Abstract

The glucose sensitivity of bursting electrical activity and pulsatile insulin release from pancreatic islets was determined in absence of functional KATP channels. Membrane potential, [Ca2+]i and 5- HT/insulin release were measured by intracellular recording, fura-2 fluorescence and 5-HT amperometry, respectively. Single mouse islets, bathed in tolbutamide or glibenclamide and high extracellular Ca2+ (Ca2+o), displayed bursting activity and concomitant fast [Ca2+]i and 5-HT/insulin oscillations. Sulphonylurea block of KATP channel current was unaffected by raising Ca2+o. Raising glucose or α-ketoisocaproic acid (KIC) concentration from 3 to 30 mM increased spiking activity and burst plateau duration. Staurosporine did not impair glucose potentiation of electrical activity, ruling out the involvement of serine/threonine kinases. Glucose enhanced both [Ca2+]i and 5-HT/insulin oscillatory activity, causing a ~ 3-fold increase in overall 5-HT release rate. Cells lacking bursting activity in high Ca2+o and low glucose (or KIC) developed a pattern of intensified spiking in response to 11 mM glucose. It is concluded that β-cells exhibit graded oscillatory electrical and secretory responses to glucose in absence of functional KATP channels. This suggests that, under physiological conditions, early glucose sensing may involve other channels besides the KATP channel.