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Nogo-A Downregulation Improves Insulin Secretion in Mice

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 antagonis...

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Autores principales: Bonal, Claire B., Baronnier, Delphine E., Pot, Caroline, Benkhoucha, Mahdia, Schwab, Martin E., Lalive, Patrice H., Herrera, Pedro L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636604/
https://www.ncbi.nlm.nih.gov/pubmed/23274909
http://dx.doi.org/10.2337/db12-0949
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author Bonal, Claire B.
Baronnier, Delphine E.
Pot, Caroline
Benkhoucha, Mahdia
Schwab, Martin E.
Lalive, Patrice H.
Herrera, Pedro L.
author_facet Bonal, Claire B.
Baronnier, Delphine E.
Pot, Caroline
Benkhoucha, Mahdia
Schwab, Martin E.
Lalive, Patrice H.
Herrera, Pedro L.
author_sort Bonal, Claire B.
collection PubMed
description 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.
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spelling pubmed-36366042014-05-01 Nogo-A Downregulation Improves Insulin Secretion in Mice Bonal, Claire B. Baronnier, Delphine E. Pot, Caroline Benkhoucha, Mahdia Schwab, Martin E. Lalive, Patrice H. Herrera, Pedro L. Diabetes Original Research 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. American Diabetes Association 2013-05 2013-04-16 /pmc/articles/PMC3636604/ /pubmed/23274909 http://dx.doi.org/10.2337/db12-0949 Text en © 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.
spellingShingle Original Research
Bonal, Claire B.
Baronnier, Delphine E.
Pot, Caroline
Benkhoucha, Mahdia
Schwab, Martin E.
Lalive, Patrice H.
Herrera, Pedro L.
Nogo-A Downregulation Improves Insulin Secretion in Mice
title Nogo-A Downregulation Improves Insulin Secretion in Mice
title_full Nogo-A Downregulation Improves Insulin Secretion in Mice
title_fullStr Nogo-A Downregulation Improves Insulin Secretion in Mice
title_full_unstemmed Nogo-A Downregulation Improves Insulin Secretion in Mice
title_short Nogo-A Downregulation Improves Insulin Secretion in Mice
title_sort nogo-a downregulation improves insulin secretion in mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636604/
https://www.ncbi.nlm.nih.gov/pubmed/23274909
http://dx.doi.org/10.2337/db12-0949
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