Summary
Mouse islets were used to study how glucose modulates arginine stimulation of insulin release. At 3 mmol/l glucose, arginine (20 mmol/l) decreased the resting membrane potential of B cells by about 10 mV, but did not evoke electrical activity. This depolarisation was accompanied by a slight but rapid acceleration of 86Rb+ efflux and 45Ca2+ influx. However, 45Ca2+ efflux and insulin release increased only weakly and belatedly. When the membrane was depolarised by threshold (7 mmol/l) or stimulatory (10–15 mmol/l) concentrations of glucose, arginine rapidly induced or augmented electrical activity, markedly accelerated 86Rb+ efflux, 45Ca2+ influx and efflux, and triggered a strong and fast increase in insulin release. When glucose-induced depolarisation of the B-cell membrane was prevented by diazoxide, arginine lost all effects but those produced at low glucose. However, the delayed increase in release still exhibited some glucose-dependency. In contrast, depolarisation by tolbut amide, at low glucose, largely mimicked the permissive effect of high glucose. Depolarisation by high K+ also amplified arginine stimulation of insulin release, but did not accelerate it as did glucose or tolbutamide. Omission of extracellular Ca2+ abolished the releasing effect of arginine under all conditions. The results thus show that the permissive action of glucose mainly results from its ability to depolarise the B-cell membrane. It enables the small depolarisation by arginine itself to activate Ca channels more rapidly and efficiently. Changes in the metabolic state of B cells may also contribute to this permissive action by increasing the efficacy of the initiating signal triggered by arginine.
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Hermans, M.P., Schmeer, W. & Henquin, J.C. The permissive effect of glucose, tolbutamide and high K+ on arginine stimulation of insulin release in isolated mouse islets. Diabetologia 30, 659–665 (1987). https://doi.org/10.1007/BF00277325
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DOI: https://doi.org/10.1007/BF00277325