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 (pH_o or pH₁) on dynamic secretory responses of perifused rat islets to 4.2, 8.4, or 16.7 mM glucose. Reduction of pH_o 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 pH_o from 7.4 to 7.8 had no influence on the secretory response to glucose. Alteration of pH_o 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 pH₁ 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 pH₁, and not pH_o, induces parallel effects on glucose-induced electrical and secretory events.