Get access
Advertisement

Altered expression and localization of insulin receptor in proximal tubule cells from human and rat diabetic kidney

Authors

  • Rodrigo Gatica,

    1. Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Región de los Ríos, Valdivia, Chile
    2. Cell Signaling Group, Institute for Research in Biomedicine, Barcelona, Spain
    3. Universidad San Sebastián, sede Puerto Montt, Facultad de Medicina, Puerto Montt, Chile
    Search for more papers by this author
  • Romina Bertinat,

    1. Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Región de los Ríos, Valdivia, Chile
    Search for more papers by this author
  • Pamela Silva,

    1. Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Región de los Ríos, Valdivia, Chile
    Search for more papers by this author
  • Daniel Carpio,

    1. Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Región de los Ríos, Valdivia, Chile
    Search for more papers by this author
  • María José Ramírez,

    1. Departments of Nephrology and Renal Transplantation, Hospital Clinic, Barcelona, Spain
    Search for more papers by this author
  • Juan Carlos Slebe,

    1. Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Región de los Ríos, Valdivia, Chile
    Search for more papers by this author
  • Rody San Martín,

    1. Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Región de los Ríos, Valdivia, Chile
    Search for more papers by this author
  • Francisco Nualart,

    1. Departamento de Biología Celular y Centro de Microscopía Avanzada, CMA BIO BIO, Universidad de Concepción, Concepción, Chile
    Search for more papers by this author
  • Jose María Campistol,

    1. Departments of Nephrology and Renal Transplantation, Hospital Clinic, Barcelona, Spain
    Search for more papers by this author
  • Carme Caelles,

    1. Cell Signaling Group, Institute for Research in Biomedicine, Barcelona, Spain
    Search for more papers by this author
  • Alejandro J. Yáñez

    Corresponding author
    1. Instituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Región de los Ríos, Valdivia, Chile
    • Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Los robles, Isla Teja S/N, Valdivia, Chile.
    Search for more papers by this author

  • The authors declared they have no conflict of interest.

  • Rodrigo Gatica and Romina Bertinat contributed equally to this work.

Abstract

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.

Get access to the full text of this article

Ancillary