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 secretion in the perfused rat pancreas, and the insulin response to glucose and arginine in pancreases isolated from tungstate-pretreated rats were studied. Infusion 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 concentration (3.2 mM). Tungstate-induced insulin output was blocked by diazoxide, somatostatin, and amylin, suggesting several targets for tungstate at the B-cell secretory machinery. Glucagon release was not modified by tungstate. Pancreases from chronically tungstate-treated rats showed an enhanced response to glucose but not to arginine. Our results indicate that the reported reduction of glycemia caused by tungstate administration is, at least in part, due to its direct insulinotropic activity. Furthermore, chronic tungstate treatment may prime the B-cell, leading to over-response to a glucose stimulus.
Clinica Puerta de Hierro, Department of Physiology, Universidad Autónoma de Madrid, San Martin de Porres 4, 28035 Madrid, Spain.
J
J
Rodríguez-Gallardo
R A
RA
Silvestre
E M
EM
Egido
J
J
Marco
D000682:Amyloid / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D004232:Diuretics; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism* / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D058228:Islet Amyloid Polypeptide; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology; D013268:Stimulation, Chemical; D017973:Tungsten Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000682:Amyloid; D004232:Diuretics; D006727:Hormone Antagonists; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D049993:Sodium Chloride Symporter Inhibitors; D017973:Tungsten Compounds; D013004:Somatostatin; C025399:sodium tungstate(VI); D005934:Glucagon; D001120:Arginine; D005947:Glucose; D003981:Diazoxide