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Research Article Free access | 10.1172/JCI118226

Overexpression of glucose transporters in rat mesangial cells cultured in a normal glucose milieu mimics the diabetic phenotype.

C W Heilig, L A Concepcion, B L Riser, S O Freytag, M Zhu, and P Cortes

University of Rochester Medical Center, Division of Nephrology, NY 14642, USA.

Find articles by Heilig, C. in: JCI | PubMed | Google Scholar

University of Rochester Medical Center, Division of Nephrology, NY 14642, USA.

Find articles by Concepcion, L. in: JCI | PubMed | Google Scholar

University of Rochester Medical Center, Division of Nephrology, NY 14642, USA.

Find articles by Riser, B. in: JCI | PubMed | Google Scholar

University of Rochester Medical Center, Division of Nephrology, NY 14642, USA.

Find articles by Freytag, S. in: JCI | PubMed | Google Scholar

University of Rochester Medical Center, Division of Nephrology, NY 14642, USA.

Find articles by Zhu, M. in: JCI | PubMed | Google Scholar

University of Rochester Medical Center, Division of Nephrology, NY 14642, USA.

Find articles by Cortes, P. in: JCI | PubMed | Google Scholar

Published October 1, 1995 - More info

Published in Volume 96, Issue 4 on October 1, 1995
J Clin Invest. 1995;96(4):1802–1814. https://doi.org/10.1172/JCI118226.
© 1995 The American Society for Clinical Investigation
Published October 1, 1995 - Version history
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Abstract

An environment of high glucose concentration stimulates the synthesis of extracellular matrix (ECM) in mesangial cell (MC) cultures. This may result from a similar increase in intracellular glucose concentration. We theorized that increased uptake, rather than glucose concentration per se is the major determinant of exaggerated ECM formation. To test this, we compared the effects of 35 mM glucose on ECM synthesis in normal MCs with those of 8 mM glucose in the same cells overexpressing the glucose transporter GLUT1 (MCGT1). Increasing medium glucose from 8 to 35 mM caused normal MCs to increase total collagen synthesis and catabolism, with a net 81-90% increase in accumulation. MCs transduced with the human GLUT1 gene (MCGT1) grown in 8 mM glucose had a 10-fold greater GLUT1 protein expression and a 1.9, 2.1, and 2.5-fold increase in cell myo-inositol, lactate production, and cell sorbitol content, respectively, as compared to control MCs transduced with bacterial beta-galactosidase (MCLacZ). MCGT1 also demonstrated increased glucose uptake (5-fold) and increased net utilization (43-fold), and greater synthesis of individual ECM components than MCLacZ. In addition, total collagen synthesis and catabolism were also enhanced with a net collagen accumulation 111-118% greater than controls. Thus, glucose transport activity is an important modulator of ECM formation by MCs; the presence of high extracellular glucose concentrations is not necessarily required for the stimulation of matrix synthesis.

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