Calcium, glucose and glucagon release.

Abstract

Using the isolated, perfused canine pancreas the importance of calcium for the normal secretory function of the pancreatic alpha cell was investigated. It was found that 1. increases in perfusate Ca++ from 1.3 to 4.8 mM and from 1.3 to 8.2 mM during perfusion with glucose concentrations of 25 and 150 mg/100 ml stimulate the release of both glucagon and insulin in a dose-related and a glucose-dependent fashion. The hormone responses to increases in calcium were, with few exceptions, biphasic 2. a ‘Ca++ free’ medium inhibited release of both hormones, and increases in perfusate glucose from 25 to 150 mg/100 ml were unable to suppress glucagon or to stimulate insulin. Addition of calcium (8.2 mM) resulted in re-establishment of the normal regulatory role of glucose upon release of both hormones, now being in a hyperactivated state by the high Ca++ concentration; 3. sudden Ca++ depletion of the perfusate from 2 mM at a glucose concentration of 200 mg/100 ml inhibited immediately the release of both hormones to very low levels, which remained low until the addition of Ca++ (2 mM). Ca++ is therefore an essential requirement for the normal secretory process of pancreatic glucagon, possibly involving uptake and accumulation within the A cell, as established for the B cell. It is suggested that Ca++ exerts its effect on the microtubular microfilamentous system.