Oral tungstate treatment improves only transiently alteration of glucose metabolism in a new rat model of type 2 diabetes

被引:21
作者
Fierabracci, V
De Tata, V
Pocai, A
Novelli, M
Barberà, A
Masiello, P
机构
[1] Univ Pisa, BMIE, Dipartimento Patol Sperimentale, Scuola Med, I-56126 Pisa, Italy
[2] Rockefeller Univ, Lab Metab Dis, New York, NY 10021 USA
关键词
experimental diabetes; tungstate; glucose tolerance test; insulin secretion; insulin resistance; isolated adipocytes;
D O I
10.1385/ENDO:19:2:177
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:177 / 184
页数:8
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