The permissive effect of glucose, tolbutamide and high K+ on arginine stimulation of insulin release in isolated mouse islets.
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 tolbutamide, 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.
Hermans
M P
MP
Unité de Diabétologie et Nutrition, University of Louvain, Faculty of Medicine, Brussels, Belgium.
Schmeer
W
W
Henquin
J C
JC
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D046508:Culture Techniques; D003981:Diazoxide / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D005950:Glucose Solution, Hypertonic / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D014044:Tolbutamide / Q000494:pharmacology*
D005950:Glucose Solution, Hypertonic; D007328:Insulin; D001120:Arginine; D014044:Tolbutamide; D005947:Glucose; D003981:Diazoxide; D011188:Potassium