Gluconeogenesis in non-obese diabetic (NOD) mice: In vivo effects of vanadate treatment on hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinase
Gluconeogenesis in non-obese diabetic (NOD) mice: In vivo effects of vanadate treatment on hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinase
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DOI：
10.1016/s0026-0495(00)90132-x
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发表时间：
2000-03-01
影响因子：
9.8
通讯作者：
Meyerovitch, J
中科院分区：
文献类型：
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作者：
Mosseri, R;Waner, T;Meyerovitch, J
使用口服钒酸盐研究了糖异生对非肥胖糖尿病 (NOD) 小鼠高血糖的影响。钒酸盐化合物已被证明可以模仿胰岛素的许多作用；然而，人们对确切的机制知之甚少。本研究的目的是（1）阐明钒酸盐的体内作用，并评估其降糖作用依赖于最小浓度胰岛素存在的可能性； (2) 评估施用钒酸盐对关键的肝糖异生酶、葡萄糖-6-磷酸酶 (G-6-Pase) 和磷酸烯醇丙酮酸羧激酶 (PEPCK) 以及葡萄糖-6-磷酸脱氢酶 (G-6-PDH) 的影响。尽管血清钒酸盐浓度有效（26.2 +/- 1.6 μmol/L），但钒酸盐导致血糖显着降低，但未能使其正常化。治疗开始两周后，对照组（C）、胰岛素（I）、钒酸盐（V）以及钒酸盐和胰岛素联合（V + I）组的血糖水平分别为26.0 +/- 1.8、21.7 +/- 3.0、16.0 +/- 1.6和14.3 +/- 2.3 mmol/L（P < .001），G-6-Pase活性显着降低钒酸盐（C vV 中 622 +/- 134 v365 +/- 83 nmol/min/mg 蛋白质，P < .05）。 PEPCK 活性也显着降低（C、I、V 和 V + I 组分别为 844 +/- 370、623 +/- 36、337 +/- 43 和 317 +/- 75 nmol/min/mg，P < .001）。治疗组之间的肝糖原储备和 G-6-PDH 活性没有显着差异。我们的研究表明，钒酸盐抑制肝脏 G-6-Pase 和 PEPCK 活性在降低 NOD 小鼠血糖水平方面发挥着重要作用。版权所有 (C) 2000 W.B.桑德斯公司。
The contribution of gluconeogenesis to hyperglycemia in non-obese diabetic (NOD) mice has been investigated using oral vanadate administration. Vanadate compounds have been shown to mimic many actions of insulin; however, the exact mechanism is poorly understood. The aims of the present study were (1) to elucidate vanadate's action In vivo, and to assess the possibility that its glucose-reducing effect is dependent on the presence of a minimal concentration of insulin; and (2) to evaluate the effects of vanadate administration on the key hepatic gluconeogenesis enzymes, glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK), as well as glucose-6-phosphate dehydrogenase (G-6-PDH). Vanadate caused a significant reduction in blood glucose but failed to normalize it, despite effective serum vanadate concentrations (26.2 +/- 1.6 mu mol/L). Two weeks after initiation of treatment, blood glucose levels were 26.0 +/- 1.8, 21.7 +/- 3.0, 16.0 +/- 1.6, and 14.3 +/- 2.3 mmol/L in the control (C), insulin (I), vanadate (V), and combined vanadate and insulin (V + I) groups, respectively(P < .001), G-6-Pase activity was significantly reduced by vanadate (622 +/- 134 v365 +/- 83 nmol/min/mg protein in C vV, P < .05). PEPCK activity was also significantly reduced (844 +/- 370, 623 +/- 36, 337 +/- 43, and 317 +/- 75 nmol/min/mg in the C, I, V, and V + I groups, respectively, P < .001). No significant differences in the hepatic glycogen stores and G-6-PDH activity were noted between treatment groups. Our study suggests that the inhibition of hepatic G-6-Pase and PEPCK activity by vanadate plays an important role in reducing blood glucose levels in NOD mice. Copyright (C) 2000 by W.B. Saunders Company.