The stimulus-secretion coupling of glucose-induced insulin release. XLII. Effects of extracellular pH on insulin...

Changes in extracellular pH affected insulin output from pancreatic islets stimulated with either glucose or alpha-ketoisocaproate. The extracellular pH at which the highest secretory response occurred was not identical in all cases, being shifted to alkaline values as the concentration of the nutrient secretagogue was increased. The output of insulin correlated with the nutrient-induced increment in 45Ca net uptake, but not with the rate of nutrient oxidation. By reference to changes in intracellular pH observed in islets exposed to either acidic media or increasing concentrations of alpha-ketoisocaproate, and taking into account a titration curve for the buffering capacity of islet homogenates, the optimal intracellular pH for insulin release was found to approximate a value of 0.09 pH unit below basal pH. It is postulated that, in the process of nutrient-induced insulin release, modest changes in intracellular pH participate in the multifactorial coupling between metabolic, ionic and secretory events.