At low glucose arginine stimulates and sulfonylureas or K+ depolarization inhibit glucagon secretion by perifused mouse islets

Background and aims:

Like pancreatic beta-cells pancreatic alpha-cells release their peptide hormone by depolarization-triggered exocytosis. However, sulfonylureas have been described to inhibit glucagon release, even though alpha-cells express K_ATP channels. Here, we have investigated the role of depolarizing stimuli and glucose on the interaction between alpha- and beta-cells within isolated islets.

Methods:

Batches of 50 freshly isolated NMRI mouse islets were perifused with a HEPES-buffered Krebs-Ringer medium (2 mg/ml BSA) saturated with 95% O₂ and 5% CO₂, which contained the respective secretagogues. The contents of insulin and of glucagon were determined by ELISA from the same samples of the fractionated efflux.

Results:

Decreasing the glucose concentration after 60 min of perifusion with 10 mM glucose to 1 mM led to a transient increase of glucagon secretion before the insulin secretion was diminished. Raising subsequently the glucose concentration from 1 to 30 mM increased the insulin secretion before the glucagon secretion was diminished. In the presence of 1 mM glucose 20 mM arginine had a moderate stimulatory effect on glucagon secretion but not on insulin secretion. Adding either sulfonylureas (30µM gliclazide or 500µM tolbutamide) or 15 mM KCl to the perifusion medium increased insulin secretion before it diminished glucagon secretion.

Conclusion:

Stimulated release of glucagon appears to be an autonomous function of the alpha-cells, which can be abrogated by the paracrine effect of concomitantly stimulated insulin release.

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