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Altered expression and localization of insulin receptor in proximal tubule cells from human and rat diabetic kidney
Author(s) -
Gatica Rodrigo,
Bertinat Romina,
Silva Pamela,
Carpio Daniel,
Ramírez María José,
Slebe Juan Carlos,
Martín Rody San,
Nualart Francisco,
Campistol Jose María,
Caelles Carme,
Yáñez Alejandro J.
Publication year - 2013
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24406
Subject(s) - endocrinology , medicine , diabetic nephropathy , kidney , diabetes mellitus , phosphoenolpyruvate carboxykinase , insulin , receptor , biology , enzyme , biochemistry
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.