The authors declared they have no conflict of interest.
Article first published online: 22 JAN 2013
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 3, pages 639–649, March 2013
How to Cite
Gatica, R., Bertinat, R., Silva, P., Carpio, D., Ramírez, M. J., Slebe, J. C., Martín, R. S., Nualart, F., Campistol, J. M., Caelles, C. and Yáñez, A. J. (2013), Altered expression and localization of insulin receptor in proximal tubule cells from human and rat diabetic kidney. J. Cell. Biochem., 114: 639–649. doi: 10.1002/jcb.24406
Rodrigo Gatica and Romina Bertinat contributed equally to this work.
- Issue published online: 22 JAN 2013
- Article first published online: 22 JAN 2013
- Accepted manuscript online: 11 OCT 2012 07:01AM EST
- Manuscript Accepted: 21 SEP 2012
- Manuscript Received: 27 JUL 2012
- Fondo Nacional de Investigación Científica y Tecnológica (FONDECYT). Grant Number: 1090694
- MINECO. Grant Number: SAF2010-21682
- INSULIN RECEPTOR;
- DIABETIC NEPHROPATHY;
- HUMAN KIDNEY;
- PROXIMAL TUBULE;
Diabetes is the major cause of end stage renal disease, and tubular alterations are now considered to participate in the development and progression of diabetic nephropathy (DN). Here, we report for the first time that expression of the insulin receptor (IR) in human kidney is altered during diabetes. We detected a strong expression in proximal and distal tubules from human renal cortex, and a significant reduction in type 2 diabetic patients. Moreover, isolated proximal tubules from type 1 diabetic rat kidney showed a similar response, supporting its use as an excellent model for in vitro study of human DN. IR protein down-regulation was paralleled in proximal and distal tubules from diabetic rats, but prominent in proximal tubules from diabetic patients. A target of renal insulin signaling, the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK), showed increased expression and activity, and localization in compartments near the apical membrane of proximal tubules, which was correlated with activation of the GSK3β kinase in this specific renal structure in the diabetic condition. Thus, expression of IR protein in proximal tubules from type 1 and type 2 diabetic kidney indicates that this is a common regulatory mechanism which is altered in DN, triggering enhanced gluconeogenesis regardless the etiology of the disease. J. Cell. Biochem. 114: 639–649, 2013. © 2012 Wiley Periodicals, Inc.