Effects of sodium tungstate on insulin and glucagon secretion in the perfused rat pancreas

Both the direct effect of sodium tungstate on insulin and glucagon secretio n in the perfused rat pancreas, and the insulin response to glucose and arg inine in pancreases isolated from tungstate-pretreated rats were studied. I nfusion of tungstate stimulated insulin output in a dose-dependent manner, The insulinotropic effect of tungstate was observed at normal (5.5 mM), and moderately high (9 mM) glucose concentrations, but not at a low glucose co ncentration (3.2 mM). Tungstate-induced insulin output was blocked by diazo xide, somatostatin, and amylin, suggesting several targets for tungstate at the B-cell secretory machinery. Glucagon release was not modified by tungs tate. Pancreases from chronically tungstate-treated rats showed an enhanced response to glucose but not to arginine. Our results indicate that the rep orted reduction of glycemia caused by tungstate administration is, at least in part, due to its direct insulinotropic activity. Furthermore, chronic t ungstate treatment may prime the B-cell, leading to over-response to a gluc ose stimulus. (C) 2000 Elsevier Science B.V. All rights reserved.