Nogo-A downregulation improves insulin secretion in mice

Article Article scientifique Article Nogo-A downregulation improves insulin secretion in mice eng 2013 author Bonal Claire Brune 502660 author Baronnier Caffe Delphine 713168 author Pot Caroline 96720 author Benkhoucha Mahdia 561017 author Schwab Martin E author Lalive d'Epinay Patrice 636926 author Herrera Pedro Luis 23981 1443-1452 10.2337/db12-0949 23274909 0012-1797 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. Animals Antibodies, Neutralizing/adverse effects/therapeutic use Carbachol/pharmacology Cholinergic Agonists/pharmacology Diabetes Mellitus, Type 2/drug therapy/metabolism/pathology Down-Regulation Hyperglycemia/prevention & control Hypoglycemia/prevention & control Hypoglycemic Agents/adverse effects/therapeutic use Insulin/secretion Insulin-Secreting Cells/drug effects/metabolism/pathology/secretion Islets of Langerhans/drug effects/innervation/metabolism/secretion Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Mutant Strains Molecular Targeted Therapy Myelin Proteins/antagonists & inhibitors/genetics/metabolism Parasympathetic Nervous System/drug effects Tissue Culture Techniques Up-Regulation/drug effects Dewey 576.5 Dewey 616.07 135 Département de médecine génétique et développement 21D 137 Département de pathologie et immunologie 21F false 588 Groupe Pot-Kreis Caroline 931 505 Scléroses en plaques, neuroimmunologie, encéphalite autoimmune expérimentale 843 272 Types cellulaires pancréatiques pendant l'ontogénèse 522 Diabetes 62 5 a4467800-69b0-4e7a-8b29-3c7283a4b375 Article (Published version) Public 1443.full.pdf 1035309 application/pdf openAccess Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Nogo-A downregulation improves insulin secretion in mice	Diabetes	2013	622	247
β-cell regeneration: the pancreatic intrinsic faculty	Trends in endocrinology and metabolism	2011	634	653
Experimental models of beta-cell regeneration	Biochemical Society transactions	2008	615	635
Genes controlling pancreas ontogeny	The International journal of developmental biology	2008	556	1

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Bonal, Claire Brune