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 language | English |
|---|---|
| Pages (from-to) | 23537-23541 |
| Number of pages | 5 |
| Journal | Journal of Biological Chemistry |
| Volume | 266 |
| Issue number | 35 |
| State | Published - Dec 15 1991 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Glucose-induced increase in cytoplasmic pH in pancreatic β-cells is mediated by Na+/H+ exchange, an effect not dependent on protein kinase C. / Juntti-Berggren, Lisa; Arkhammar, Per; Nilsson, Thomas; Rorsman, Patrik; Berggren, Per Olof.
In: Journal of Biological Chemistry, Vol. 266, No. 35, 15.12.1991, p. 23537-23541.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glucose-induced increase in cytoplasmic pH in pancreatic β-cells is mediated by Na+/H+ exchange, an effect not dependent on protein kinase C
AU - Juntti-Berggren, Lisa
AU - Arkhammar, Per
AU - Nilsson, Thomas
AU - Rorsman, Patrik
AU - Berggren, Per Olof
PY - 1991/12/15
Y1 - 1991/12/15
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0026355858&partnerID=8YFLogxK
M3 - Article
VL - 266
SP - 23537
EP - 23541
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 35
ER -