钒对链脲佐菌素诱导的糖尿病大鼠白色脂肪组织中葡萄糖转运蛋白4转位的体内效应缺失

Cam M C, Brownsey R W, Rodrigues B, McNeill J H

Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.

Metabolism. 2001 Jun;50(6):674-80. doi: 10.1053/meta.2001.23296.

Vanadium treatment, in vivo, corrects the severe hyperglycemia observed in streptozotocin (STZ)-diabetic rats. A number of metabolic effects of vanadium have been demonstrated in vitro and might contribute importantly to normalization of glucose homeostasis. However, many in vitro effects of vanadium occur at concentrations substantially higher than those achieved in vivo. Effects of vanadium on white adipose tissue have been particularly well characterized in vitro. To examine the relationship between in vitro and in vivo actions of vanadium, we examined the effects of vanadium treatment on acute glucose tolerance and adipose tissue GLUT4 control in vivo. In agreement with previous studies, vanadium treatment of STZ-diabetic rats restored normoglycemia with no appreciable restoration of insulin secretion. GLUT4 expression in white adipose tissue was reduced by 22% in STZ-diabetic rats compared with controls. Vanadium treatment did not significantly alter GLUT4 expression in controls, but completely restored normal expression levels in STZ-diabetic rats. In overnight-fasted control animals, GLUT4 translocation to the plasma membrane (PM) was maximally elevated (by 50%) in adipose tissue within 5 to 10 minutes after an intravenous (IV) glucose challenge. No glucose-induced translocation of GLUT4 was detected in diabetic rats, and peak PM GLUT4 content was 40% lower than in controls. Vanadium treatment did not increase peak PM GLUT4 content in either control or diabetic animals in response to a glucose load. Finally, the suppression of whole-body acute glucose tolerance in diabetic animals was only partially normalized by vanadium treatment. We conclude: (1) that concentrations of vanadium effective for maintaining normoglycemia in vivo (typically below 30 micromol/L) promote normal GLUT4 expression, but do not influence the subcellular localization of GLUT4 in white adipose tissue and (2) that in vivo effects of vanadium may not necessarily reflect the actions observed in vitro at supraphysiologic concentrations.

钒治疗在体内可纠正链脲佐菌素（STZ）诱导的糖尿病大鼠中观察到的严重高血糖症。钒的许多代谢作用已在体外得到证实，可能对葡萄糖稳态的正常化起重要作用。然而，钒在体外的许多作用发生在远高于体内所能达到的浓度下。钒对白色脂肪组织的作用在体外已得到特别充分的表征。为了研究钒的体外和体内作用之间的关系，我们在体内研究了钒治疗对急性葡萄糖耐量和脂肪组织葡萄糖转运蛋白4（GLUT4）调控的影响。与先前的研究一致，钒治疗STZ诱导的糖尿病大鼠可恢复正常血糖，但胰岛素分泌无明显恢复。与对照组相比，STZ诱导的糖尿病大鼠白色脂肪组织中GLUT4的表达降低了22%。钒治疗对对照组的GLUT4表达没有显著影响，但完全恢复了STZ诱导的糖尿病大鼠的正常表达水平。在过夜禁食的对照动物中，静脉注射（IV）葡萄糖激发后5至10分钟内，脂肪组织中GLUT4向质膜（PM）的转位最大程度升高（50%）。在糖尿病大鼠中未检测到葡萄糖诱导的GLUT4转位，且PM处GLUT4的峰值含量比对照组低40%。钒治疗在葡萄糖负荷下对对照动物或糖尿病动物的PM处GLUT4峰值含量均无增加作用。最后，钒治疗仅部分纠正了糖尿病动物全身急性葡萄糖耐量的抑制。我们得出结论：（1）在体内维持正常血糖有效的钒浓度（通常低于30微摩尔/升）可促进正常的GLUT4表达，但不影响白色脂肪组织中GLUT4的亚细胞定位；（2）钒的体内作用不一定反映在超生理浓度下体外观察到的作用。