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Diabetes 55:1826-1831, 2006
DOI: 10.2337/db05-1438
© 2006 by the American Diabetes Association
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Diabetic Nephropathy Is Associated With Gene Expression Levels of Oxidative Phosphorylation and Related Pathways

Chunmei Huang1, Youngki Kim1, M. Luiza Caramori2, Jason H. Moore3, Stephen S. Rich4, Josyf C. Mychaleckyj4, Paul C. Walker1, and Michael Mauer1

1 Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota
2 Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
3 Computational Genetics Laboratory, Department of Genetics, Dartmouth Medical School, Lebanon, New Hampshire
4 Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Address correspondence and reprint requests to Michael Mauer, MD, Paediatric Nephrology, MMC 491 UMHC, 420 Delaware St. S.E., Minneapolis, MN 55455. E-mail: mauer002{at}umn.edu

Abbreviations: ROS, reactive oxygen species

The in vitro behavior of skin fibroblasts from patients with or without diabetic nephropathy is associated with diabetic nephropathy risk. Here we compared skin fibroblast gene expression profiles from two groups of type 1 diabetic patients: 20 with very fast ("fast-track") versus 20 with very slow ("slow-track") rates of development of diabetic nephropathy lesions. Gene expression profiles of skin fibroblasts grown in 25 mmol/l glucose for 36 h were assessed by Affymetrix HG-U133A GeneChips to determine the proportion of genes in a given biological pathway that were directionally consistent in their group differences. Five pathways reached statistical significance. All had significantly greater proportions of genes with higher expression levels in the fast-track group. These pathways, the first four of which are closely related and have overlapping genes, included oxidative phosphorylation (P < 0.001), electron transport system complex III (P = 0.017), citrate cycle (P = 0.037), propanoate metabolism (P = 0.044), and transcription factors (P = 0.046). These results support the concept that oxidative phosphorylation and related upstream pathways may be important in the pathogenesis of diabetic nephropathy. Whether these findings reflect inherent genetic cellular characteristics, "cell memory," or both requires further study.


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2006 by the American Diabetes Association.