Differentiation between the short and long term effects of glucose on the intracellular calcium content of the pancreatic beta-cell.

The problem of how glucose affects the intracellular (La3+-nondisplaceable) calcium content of pancreatic beta-cells was approached by combining measurements of 45Ca in ob/ob-mouse islets loaded to isotopic equilibrium with determinations of calcium using electrothermal atomic absorption spectroscopy. Whereas short term changes of the glucose concentration induced marked alterations of insulin release, the islet content of intracellular 45Ca was remarkably stable. The chronic actions of glucose differed from the acute ones in being readily demonstrable and sometimes resulting even in a suppression of the calcium content. Thus, after 7 days of culture in 20 mM glucose, the amount of intracellular calcium was actually lower than when the islets were cultured at 5.5 mM glucose. The long term effect of glucose in suppressing the islet content of intracellular calcium was associated with degranulation and loss of immunoreactive insulin, indicated both from staining of the beta-cells and measurements of the extracted hormone by RIA. The previously unknown ability of glucose to suppress the islet content of intracellular calcium may consequently result from mobilization of the secretory granules.