title: Oral tungstate treatment improves only transiently alteration of glucose metabolism in a new rat model of type 2 diabetes.
abstract: It has been shown that tungstate is an effective hypoglycemic agent in several animal models of diabetes. In this study, we examined the effectiveness of oral tungstate treatment in a new experimental diabetic syndrome, induced by streptozotocin (STZ) and nicotinamide in adult rats, that shares several features with human type 2 diabetes. Sodium tungstate was administered in the drinking water (2 mg/mL) of control and diabetic rats for 15, 30, 60, and 90 d. Glucose metabolism was explored in vivo by intravenous glucose tolerance test. Insulin secretion and action were assessed in vitro in the isolated perfused pancreas and isolated adipocytes, respectively. Two weeks of tungstate treatment did not modify the moderate hyperglycemia of diabetic rats but reduced their intolerance to glucose, owing to an enhancement of postloading insulin secretion. However, this effect was transient, since it declined after 30 d and vanished after 60 and 90 d of tungstate administration, whereas a trend toward a reduction in basal hyperglycemia was observed on prolonged treatment. Oral tungstate was unable to modify glucose-stimulated insulin secretion in the isolated perfused pancreas, as well as muscle glycogen levels, hepatic glucose metabolism, and insulin-stimulated lipogenesis in isolated adipocytes. Nevertheless, the decreased insulin content of pancreatic islets of diabetic rats was partially restored on prolonged tungstate treatment. In conclusion, in the STZ-nicotinamide model of diabetes, tungstate was unable to permanently correct the alterations in glucose metabolism, despite some indirect evidence of a trophic effect on beta-cells. The ineffectiveness of tungstate could be related to the absence, in this diabetic syndrome, of relevant metabolic alterations in the liver, which thus appear to constitute the major target of tungstate action.
authors.affiliation: Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia, University of Pisa, Italy.
authors.forename: Vanna
authors.initials: V
authors.lastname: Fierabracci
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Tata
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pocai
authors.forename: Michela
authors.initials: M
authors.lastname: Novelli
authors.forename: Albert
authors.initials: A
authors.lastname: Barberà
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Masiello
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004334:Drug Administration Schedule; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D017973:Tungsten Compounds / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D017973:Tungsten Compounds; D006003:Glycogen; D005947:Glucose; C045951:tungstate