Nogo-A Downregulation Improves Insulin Secretion in Mice
- Claire B. Bonal1,
- Delphine E. Baronnier1,
- Caroline Pot2,3,
- Mahdia Benkhoucha2,
- Martin E. Schwab4,5,
- Patrice H. Lalive2,3,6 and
- Pedro L. Herrera1⇑
- 1Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- 2Division of Neurology, Department of Neurosciences, Geneva University Hospital, Geneva, Switzerland
- 3Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland
- 4Brain Research Institute, University of Zurich, Zurich, Switzerland
- 5Department of Biology, Swiss Federal Institute of Technology, Zurich, Switzerland
- 6Division of Laboratory Medicine, Department of Genetic and Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland
- Corresponding author: Pedro L. Herrera, .
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.
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.
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