Effects of amino acids on membrane potential and 86Rb+ fluxes in pancreatic beta-cells.
The membrane potential of beta-cells was studied with microelectrodes in mouse islets and their potassium permeability was evaluated by measuring 86Rb+ fluxes in rat islets. In the absence of glucose, L-leucine, its metabolite ketoisocaproate, and its nonmetabolized analogue 2-aminonorbornane-2-carboxylic acid (BCH) depolarized beta-cells and triggered bursts of electrical activity like glucose. The effect of leucine was weak, but was potentiated by a low concentration of glucose or by theophylline; the effect of ketoisocaproate was stronger and faster than that of an equimolar concentration of glucose. Arginine alone produced only a fast depolarization of beta-cells, insufficient to trigger electrical activity. Leucine and arginine potentiated the activity induced by glucose. In a glucose-free medium, alanine only slightly depolarized beta-cells, whereas isoleucine and phenylalanine had no effect. Leucine, ketoisocaproate, and BCH reversibly decreased 86Rb+ efflux from islets perifused in the absence of glucose and increased 86Rb+ uptake. By contrast, both in the absence or presence of glucose, arginine increased 86Rb+ efflux and decreased 86Rb+ uptake. It is proposed that leucine, ketoisocaproate, and BCH, as glucose, depolarize beta-cells by decreasing their potassium permeability, whereas arginine acts differently. The appearance of bursts of electrical activity with secretagogues unrelated to glucose suggests that they reflect an intrinsic property of the beta-cell membrane.
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology*; D007930:Leucine / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D011188:Potassium / Q000378:metabolism*; D011868:Radioisotopes; D051381:Rats; D012413:Rubidium / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology
D011868:Radioisotopes; D001120:Arginine; D013806:Theophylline; D007930:Leucine; D005947:Glucose; D012413:Rubidium; D011188:Potassium