title: Glucose transporters in diabetic nephropathy.
abstract: 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.
authors.affiliation: Departments of Internal Medicine and Physiology, University of Michigan, Ann Arbor, MI 48109-0676, USA. fbrosius@umich.edu
authors.forename: Frank C
authors.initials: FC
authors.lastname: Brosius
authors.forename: Charles W
authors.initials: CW
authors.lastname: Heilig
mesh_terms: D000818:Animals; D003929:Diabetic Neuropathies / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D005920:Glomerular Mesangium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D015398:Signal Transduction
chemical_list: D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D005947:Glucose
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