Modification of glucose-induced insulin release by alteration of pH

Protons (H+) generated by glucose metabolism have been proposed to serve as a coupling factor between cationic and secretory events in the B-cell. We have examined the influence of alteration of extracellular or intracellular pH (pHo or pHi) on dynamic secretory responses of perfused rat islets to 4.2, 8.4, or 16.7 mM glucose. Reduction of pHo from 7.4 to 7.0 inhibited the secretory response to 16.7, but not 8.4 mM glucose, by 47% during the 30-min period following medium change. Increase of pHo from 7.4 to 7.8 had no influence on the secretory response to glucose. Alteration of pHo had no influence on basal insulin release in the presence of 4.2 mM glucose. Sulfamerazine (5 mM), a permeable weak acid, augmented the secretory response to 8.4 mM glucose by 60% but had no influence on the response to 16.7 mM glucose. In contrast, imidazole (10 mM), a permeable weak base, inhibited the secretory response to both 8.4 (62%) and 16.7 mM (72%) glucose. Another weak base, NH4Cl (20 mM), also inhibited the secretory response to 8.4 (61%) and 16.7 mM (68%) glucose. Alteration of pHi by sulfamerazine and imidazole did not alter basal insulin release in the presence of 4.2 mM glucose. A comparison of the present findings to those obtained for the influence of pH on glucose-induced electrical activity indicates that alteration of pHi, and not pHo, induces parallel effects on glucose-induced electrical and secretory events.