Alpha cell depolarization directly translates into elevated glucagon secretion

Background and aims:

Like pancreatic beta cells, pancreatic alpha cells release their hormone by depolarization-induced exocytosis. So, is the inverse glucose dependence of glucagon secretion due to different fuel recognition or to different electrical events?

Methods:

Insulin and glucagon were determined by ELISA from the same efflux fraction of batch-perifused NMRI mouse islets. Alpha-cells were isolated from these islets by incubation with alloxan and culturing for 24h. In such cells the membrane potential was determined by patch-clamping and cytosolic Ca2+ concentration ([Ca2+]i) by microfluorometry.

Results:

Alloxan-surviving islet cells were considered as bona fide alpha cells when they reacted to both, arginine and glutamate. In these cells 15 mM KCl depolarized the plasma membrane potential by 11 mV and 40 mM KCl by 32 mV, which was ca. 10 mV less than the depolarizing effect in single beta cells. 500µM tolbutamide was of variable depolarizing efficiency, whereas it invariably led to the typical wave and spike depolarization in beta cells. The different strength of the depolarizing effect was mirrored by the different increases of [Ca2+]i in alpha cells. In the presence of 1 mM glucose and 1µM clonidine (to block insulin secretion), 500µM tolbutamide had a modest stimulatory effect, whereas 40 mM KCl led to marked and lasting increase of glucagon secretion.

Conclusion:

When beta cell activity is inhibited, strong depolarization by KCl stimulates strong glucagon secretion by alpha cells, whereas sulfonylureas exert only a modest stimulatory effect, concurrent with their modest depolarizing effect in alpha cells.