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unige:32140 
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Nogo-A downregulation improves insulin secretion in mice |
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| Authors | ||
| Published in | Diabetes. 2013, vol. 62, no. 5, p. 1443-52 | |
| 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. | |
| Keywords | 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 | |
| Identifiers | DOI: 10.2337/db12-0949 PMID: 23274909 | |
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| Research groups | Types cellulaires pancréatiques pendant l'ontogénèse (522) Scléroses en plaques, neuroimmunologie, encéphalite autoimmune expérimentale (843) Groupe Pot-Kreis Caroline (931) | |
| Citation (ISO format) | BONAL, Claire Brune et al. Nogo-A downregulation improves insulin secretion in mice. In: Diabetes, 2013, vol. 62, n° 5, p. 1443-52. https://archive-ouverte.unige.ch/unige:32140 |
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