Glucose-induced increase in cytoplasmic pH in pancreatic β-cells is mediated by Na+/H+ exchange, an effect not dependent on protein kinase C

L. Juntti-Berggren, P. Arkhammar, T. Nilsson, P. Rorsman, P. O. Berggren

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Glucose-induced changes in cytoplasmic pH (pHi) were investigated using pancreatic β-cells isolated from obese hyperglycemic mice. Glucose, at concentrations above 3-5 mM, depolarized the β-cell and increased pHi, cytoplasmic free Ca2+ ([Ca2+]i), and insulin release. This increase in pHi was dependent on the presence of extracellular Na+ and was inhibited by 5-(N-ethyl-N-isopropyl) amiloride, a blocker of Na+/H+ exchange. Stimulation of protein kinase C with phorbol ester also induced an alkalinization. However, when protein kinase C activity was down-regulated, glucose stimulation still induced alkalinization. At 20 mM glucose, 10 mM NH4Cl induced a marked rise in pHi, paralleled by repolarization, inhibition of electrical activity, and decreases in both [Ca2+]i and insulin release. Reduction in [Ca2+]i was prevented by 200 μM tolbutamide, but not by 10 mM tetraethylammonium. At 4 mM glucose, NH4Cl induced a transient increase in insulin release, without changing [Ca2+]i. Exposure of β-cells to 10 mM sodium acetate caused a persistent decrease in pHi, an effect paralleled by a small transient increase in [Ca2+]i. Acidification per se did not change the β-cell sensitivity to glucose, not excluding that the activity of the ATP-regulated K+ channels may be modulated by changes in pHi.

Original languageEnglish (US)
Pages (from-to)23537-23541
Number of pages5
JournalJournal of Biological Chemistry
Volume266
Issue number35
StatePublished - Dec 1 1991

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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