Is intracellular pH a coupling factor in nutrient-stimulated pancreatic islets?
Intracellular pH (pHi) was monitored in dispersed pancreatic islet cells from rats using the fluorescent dye 2'7'bis-carboxyethyl-5'(6')-carboxyfluorescein. The addition of a weak acid (acetate, propionate or formate) provoked a rapid fall in pHi, corresponding to approximately 0.2 units, following by a slower return to the basal value. Amiloride also caused a rapid fall in pHi, but no recovery occurred in this case. Addition of NH4Cl induced a rise in pHi. Of the nutrients tested, only glyceraldehyde produced a fall in pHi, both glucose and alpha-ketoisocaproate causing a gradual and sustained rise in pHi. Insulin secretion and inositol lipid metabolism in response to nutrient stimuli were markedly inhibited by NH4Cl. The responses to non-nutrient stimuli were unaffected. Glucose-induced insulin secretion and inositol lipid metabolism were potentiated in the presence of amiloride. No such potentiation, however, was observed in the presence of weak acids. Amiloride and weak acids shared the ability to reduce the fractional outflow rate of 45Ca2+. It is concluded that pharmacological manipulations of pHi can influence certain aspects of islet cell function, such as calcium handling, though it seems unlikely that the stimulation of islets by nutrient secretagogues occurs as a result of changes in pHi.
Best
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Department of Medicine, University of Manchester Medical School.
Bone
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Meats
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Tomlinson
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D000584:Amiloride / Q000494:pharmacology; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D005452:Fluoresceins; D006863:Hydrogen-Ion Concentration; D007294:Inositol / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D050356:Lipid Metabolism; D051381:Rats
D005452:Fluoresceins; D007328:Insulin; D000643:Ammonium Chloride; C024098:6-carboxyfluorescein; D007294:Inositol; D000584:Amiloride; D002118:Calcium