Cation transport by pancreatic beta-cells: effect of 4-aminopyridine on 86Rb+ and 45Ca2+ fluxes.
The effects of 4-aminopyridine (4-AP) on insulin release, glucose oxidation and 86Rb+ and 45Ca2+ fluxes of rat isolated islets were studied. 4-AP (0.1 and 1.0 mM) did not alter the 86Rb+ fractional efflux. However, 10 mM 4-AP significantly increased the 86Rb+ fractional efflux. 10 mM 4-AP also reduced the insulin release from islets incubated over 90 min in the presence of both 6 and 16.7 mM glucose and from perifused islet in the presence of 16.7 mM glucose. 4-AP (10 mM) only transiently increased the insulin release and the 45Ca2+ fractional efflux in the presence of 6 mM glucose. The 45Ca2+ fractional efflux was not changed when the islets were perifused at higher glucose concentration. At zero, 6 or 16.7 mM glucose, 4-AP (10 mM) significantly increased the 45Ca2+ net uptake by islets incubated for 90 min. 10 mM 4-AP significantly reduced the glucose oxidation of islets incubated for 120 min in the presence of 16.7 mM glucose. The effects of 10 mM 4-AP on the dynamics of insulin release and 86Rb+ fractional efflux were poorly reversible. In conclusion, 4-AP, at concentrations that did not alter the glucose metabolism, (0.1 and 1 mM), failed to affect the K+ permeability in beta-cells as judged by the measurements of 86Rb+ fractional efflux. At higher concentrations (10 mM) 4-AP increased 86Rb+ efflux, decreased glucose metabolism and reduced insulin release.
Boschero
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Departamento de Fisiologia e Biofisica, Universidade Estadual de Campinas, S.P., Brasil.
Reis
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Dias
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Delattre
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Gonçalves
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D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002132:Calcium Radioisotopes; D002463:Cell Membrane Permeability / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes
D000631:Aminopyridines; D002132:Calcium Radioisotopes; D007328:Insulin; D012414:Rubidium Radioisotopes; D015761:4-Aminopyridine; D005947:Glucose; D011188:Potassium