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J Biol Chem. 1995 Apr 7;270(14):7915-21.

The role of metabolism, cytoplasmic Ca2+, and pH-regulating exchangers in glucose-induced rise of cytoplasmic pH in normal mouse pancreatic islets.

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Unité d'Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, Brussels, Belgium.


Intact mouse islets were loaded with 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein to study the effects of glucose on cytoplasmic pH (pHi) in pancreatic B-cells. In HCO3- buffer, glucose produced a steady-state increase in pHi that required metabolism of the sugar and was concentration-dependent between 0 and 10 mM (Km approximately 5 mM) before plateauing at a maximum value of approximately 0.2 pH units. In HEPES buffer, glucose concentrations above 7 mM caused an initial rise followed by a secondary decrease and an eventual return to about initial values. Inhibition of Ca2+ influx had little effect on the pHi changes produced by glucose in HCO3- medium, but unmasked an alkalinizing effect in HEPES buffer. Raising cytoplasmic Ca2+ by 30 mM potassium caused a larger acidification in HEPES than in HCO3- buffer, but a subsequent rise in glucose now increased pHi in both types of buffer. In the presence of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; inhibitor of HCO3-/Cl- exchange), the effect of glucose on pHi in HCO3- buffer became similar to that in HEPES buffer. After inhibition of the Na+/H+ exchanger by dimethylamiloride, glucose produced a marked and sustained fall in pHi in HEPES buffer. A similar fall was seen in HCO3- buffer only when DIDS and dimethylamiloride were present together. However, if Ca2+ influx was prevented when both exchangers were blocked, glucose increased pHi. In conclusion, the metabolism of glucose tends to increase pHi in B-cells, whereas the concomitant rise in [Ca2+]i exerts an acidifying action. In HEPES buffer, this acidifying effect of Ca2+ is offset by the operation of the Na+/H+ exchanger. In physiological HCO3- buffer, the activity of the HCO3-/Cl- exchanger overcompensates and leads to an increase in pHi.

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