title: GLUT1 and TGF-beta: the link between hyperglycaemia and diabetic nephropathy.
abstract: Recent experimental work implicates transforming growth factor-beta (TGF-beta) as an aetiologic mediator of diabetic nephropathy and the ubiquitous glucose transporter GLUT1 as an important permissive factor for the tissue injury caused by hyperglycaemia. High ambient glucose increases GLUT1 expression and glucose transport activity when compared with physiologic glucose concentrations. Treatment of rat mesangial cells with TGF-beta up-regulates GLUT1 mRNA and protein levels and significantly increases glucose uptake. Addition of neutralizing anti-TGF-beta antibody prevents the stimulatory effects of high glucose on GLUT1 expression. Cultured rat mesangial cells transduced with the human GLUT1 gene and thus overexpressing the GLUT1 protein show marked increase in glucose uptake and the synthesis of extracellular matrix molecules, even when grown in normal ambient glucose concentrations. Thus, TGF-beta and GLUT1, two proteins that are up-regulated in glomerular mesangial cells in a hyperglycaemic milieu, can influence the expression of one another. It is therefore fair to conclude that, with successful interruption of the TGF-beta-GLUT1 axis, the beneficial effects of strict glucose control on the development of diabetic nephropathy could likely be augmented.
authors.affiliation: Division of Nephrology, Department of Medicine, Virginia Commonwealth University/Medical College of Virginia and McGuire VAMC, Richmond, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mogyorósi
authors.forename: F N
authors.initials: FN
authors.lastname: Ziyadeh
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000209:etiology*; D051272:Glucose Transporter Type 1; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D009004:Monosaccharide Transport Proteins / Q000502:physiology*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; C495679:Slc2a1 protein, rat; D016212:Transforming Growth Factor beta