Effects of high extracellular K(+) concentrations, diazoxide and/or Ca(2+) deprivation upon D-glucose metabolism in pancreatic islets.
A rise in D-glucose concentration may augment insulin release independently of changes in K(+) conductance or Ca(2+) influx in pancreatic islet cells, the insulinotropic action of the hexose remaining dependent on an increased generation of high-energy phosphates. In the present study, therefore, it was investigated to which extent the procedures currently used to assess the modalities of the secretory response to D-glucose independent of its effect on ATP-sensitive K(+) channels and Ca(2+) inflow may themselves affect the catabolism of the hexose in isolated rat pancreatic islets. A rise in the extracellular K(+) concentration from 5 to 30 or 60 mM failed to significantly affect the metabolism of D-glucose. At 90 mM K(+), however, the maximal velocity of the glycolytic flux was decreased and the apparent K(m) for D-glucose lowered, without an obvious alteration of the preferential stimulation of oxidative mitochondrial events in response to a rise in D-glucose concentration. Such a preferential stimulation was abolished, however, either by diazoxide at a low, but not high, K(+) concentration or by Ca(2+) deprivation, in the absence or presence of diazoxide, at a high K(+) concentration. It is speculated that these metabolic changes may be attributable, in part at least, to an altered activity of key cytosolic (e.g. pyruvate kinase) and mitochondrial (e.g. FAD-linked glycerophosphate dehydrogenase) enzymes.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, 808 Route de Lennik, B-1070, Brussels, Belgium.
Picton
S
S
Malaisse-Lagae
F
F
Sener
A
A
D000818:Animals; D002118:Calcium / Q000172:deficiency*; D002250:Carbon Radioisotopes; D003981:Diazoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium
D002250:Carbon Radioisotopes; D007328:Insulin; D014316:Tritium; D005947:Glucose; D003981:Diazoxide; D011188:Potassium; D002118:Calcium