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Intracellular pH (pH_i) 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 pH_i, corresponding to approximately 0·2 units, followed by a slower return to the basal value. Amiloride also caused a rapid fall in pH_i, but no recovery occurred in this case. Addition of NH₄Cl induced a rise in pH_i. Of the nutrients tested, only glyceraldehyde produced a fall in pH_i, both glucose and -ketoisocaproate causing a gradual and sustained rise in pH_i.

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 pH_i 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 pH_i.

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