Brosius Frank C, Heilig Charles W
Departments of Internal Medicine and Physiology, University of Michigan, Ann Arbor, MI 48109-0676, USA.
Pediatr Nephrol. 2005 Apr;20(4):447-51. doi: 10.1007/s00467-004-1748-x. Epub 2005 Feb 17.
Changes in glucose transporter expression in glomerular cells occur early in diabetes. These changes, especially the GLUT1 increase in mesangial cells, appear to play a pathogenic role in the development of ECM expansion and perhaps other features of diabetic nephropathy. In addition, it appears that at least some diabetic patients may be predisposed to nephropathy because of polymorphisms in their GLUT1 genes. GLUT1 overexpression leads to increased glucose metabolic flux which in turn triggers the polyol pathway and activation of PKC alpha and B1. Activation of these PKC isoforms can lead directly to AP-1 induced increases in fibronectin expression and ECM accumulation. Other, more novel effects of GLUT1 on cellular hypertrophy and injury could also promote changes of diabetic nephropathy. Strategies to prevent GLUT1 overexpression could ameliorate or prevent the progression of diabetic nephropathy.
糖尿病早期肾小球细胞中的葡萄糖转运蛋白表达会发生变化。这些变化，尤其是系膜细胞中GLUT1的增加，似乎在细胞外基质扩张及糖尿病肾病的其他特征发展过程中发挥致病作用。此外，至少部分糖尿病患者可能因GLUT1基因多态性而易患肾病。GLUT1过表达导致葡萄糖代谢通量增加，进而触发多元醇途径以及PKCα和B1的激活。这些PKC亚型的激活可直接导致AP-1诱导的纤连蛋白表达增加和细胞外基质积聚。GLUT1对细胞肥大和损伤的其他更新颖的影响也可能促进糖尿病肾病的变化。预防GLUT1过表达的策略可能会改善或阻止糖尿病肾病的进展。
