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Original Research

Nogo-A Downregulation Improves Insulin Secretion in Mice

  1. Claire B. Bonal1,
  2. Delphine E. Baronnier1,
  3. Caroline Pot2,3,
  4. Mahdia Benkhoucha2,
  5. Martin E. Schwab4,5,
  6. Patrice H. Lalive2,3,6 and
  7. Pedro L. Herrera1⇑
  1. 1Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland
  2. 2Division of Neurology, Department of Neurosciences, Geneva University Hospital, Geneva, Switzerland
  3. 3Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland
  4. 4Brain Research Institute, University of Zurich, Zurich, Switzerland
  5. 5Department of Biology, Swiss Federal Institute of Technology, Zurich, Switzerland
  6. 6Division of Laboratory Medicine, Department of Genetic and Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland
  1. Corresponding author: Pedro L. Herrera, pedro.herrera{at}unige.ch.
Diabetes 2013 May; 62(5): 1443-1452. https://doi.org/10.2337/db12-0949
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Abstract

Type 2 diabetes (T2D) is characterized by β-cell dysfunction and the subsequent depletion of insulin production, usually in a context of increased peripheral insulin resistance. T2D patients are routinely treated with oral antidiabetic agents such as sulfonylureas or dipeptidyl peptidase-4 antagonists, which promote glucose- and incretin-dependent insulin secretion, respectively. Interestingly, insulin secretion may also be induced by neural stimulation. Here we report the expression of Nogo-A in β-cells. Nogo-A is a membrane protein that inhibits neurite outgrowth and cell migration in the central nervous system. We observed that Nogo-A–deficient mice display improved insulin secretion and glucose clearance. This was associated with a stronger parasympathetic input and higher sensitivity of β-cells to the cholinergic analog carbachol. Insulin secretion was also improved in diabetic db/db mice treated with neutralizing antibody against Nogo-A. Together, these findings suggest that promoting the vagal stimulation of insulin secretion through the selective inhibition of Nogo-A could be a novel therapeutic approach in T2D.

Footnotes

  • This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-0949/-/DC1.

  • Received July 17, 2012.
  • Accepted November 17, 2012.
  • © 2013 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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May 2013, 62(5)
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Nogo-A Downregulation Improves Insulin Secretion in Mice
Claire B. Bonal, Delphine E. Baronnier, Caroline Pot, Mahdia Benkhoucha, Martin E. Schwab, Patrice H. Lalive, Pedro L. Herrera
Diabetes May 2013, 62 (5) 1443-1452; DOI: 10.2337/db12-0949

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Nogo-A Downregulation Improves Insulin Secretion in Mice
Claire B. Bonal, Delphine E. Baronnier, Caroline Pot, Mahdia Benkhoucha, Martin E. Schwab, Patrice H. Lalive, Pedro L. Herrera
Diabetes May 2013, 62 (5) 1443-1452; DOI: 10.2337/db12-0949
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