Marzban Lucy, Rahimian Roshanak, Brownsey Roger W, McNeill John H
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
Endocrinology. 2002 Dec;143(12):4636-45. doi: 10.1210/en.2002-220732.
Vanadium treatment normalizes plasma glucose levels in streptozotocin-diabetic rats in vivo, but the mechanism(s) involved are still unclear. Here, we tested the hypothesis that the in vivo effects of vanadium are mediated by changes in gluconeogenesis. Diabetic rats were treated with bis(maltolato)oxovanadium(IV) (BMOV) in the drinking water (0.75-1 mg/ml, 4 wk) or, for comparison, with insulin implants (4 U/d) for the final week of study. As with insulin, BMOV lowered plasma glucose and normalized phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) mRNA in the liver and kidney of diabetic rats. To determine the importance of reducing hyperglycemia per se, diabetic rats were treated either with a single ED(50) dose of BMOV (0.1 mmol/kg, ip) or with phlorizin (900 mg/kg.d, 5 d). BMOV rapidly restored PEPCK and G-6-Pase mRNA and normalized plasma glucose in responsive (50%) diabetic rats but had no effect on the nonresponsive hyperglycemic rats. Phlorizin corrected plasma glucose but had no effect on PEPCK mRNA and only partially normalized G-6-Pase mRNA. In conclusion, 1) BMOV inhibits PEPCK mRNA expression and activity by rapid mechanisms that are not reproduced simply by correction of hyperglycemia; and 2) BMOV inhibits G-6-Pase expression by complex mechanisms that depend, in part, on correction of hyperglycemia.
钒治疗可使链脲佐菌素诱导的糖尿病大鼠体内血浆葡萄糖水平恢复正常，但其中涉及的机制仍不清楚。在此，我们检验了钒的体内作用是由糖异生变化介导的这一假说。给糖尿病大鼠饮用含双（麦芽醇根）氧钒（IV）（BMOV）的水（0.75 - 1 mg/ml，4周），或者作为对照，在研究的最后一周植入胰岛素（4 U/d）。与胰岛素一样，BMOV降低了糖尿病大鼠肝脏和肾脏中的血浆葡萄糖水平，并使磷酸烯醇式丙酮酸羧激酶（PEPCK）和葡萄糖-6-磷酸酶（G-6-Pase）的mRNA恢复正常。为了确定降低高血糖本身的重要性，给糖尿病大鼠单次注射ED（50）剂量的BMOV（0.1 mmol/kg，腹腔注射）或根皮苷（900 mg/kg·d，5天）。BMOV能迅速恢复反应性（50%）糖尿病大鼠的PEPCK和G-6-Pase mRNA，并使血浆葡萄糖恢复正常，但对无反应的高血糖大鼠没有影响。根皮苷纠正了血浆葡萄糖水平，但对PEPCK mRNA没有影响，仅部分使G-6-Pase mRNA恢复正常。总之，1）BMOV通过快速机制抑制PEPCK mRNA的表达和活性，而这种机制并非仅仅通过纠正高血糖就能重现；2）BMOV通过复杂机制抑制G-6-Pase的表达，这种机制部分依赖于高血糖的纠正。
