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Nogo-A downregulation improves insulin secretion in mice

Schwab, Martin E
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 AnimalsAntibodies, Neutralizing/adverse effects/therapeutic useCarbachol/pharmacologyCholinergic Agonists/pharmacologyDiabetes Mellitus, Type 2/drug therapy/metabolism/pathologyDown-RegulationHyperglycemia/prevention & controlHypoglycemia/prevention & controlHypoglycemic Agents/adverse effects/therapeutic useInsulin/secretionInsulin-Secreting Cells/drug effects/metabolism/pathology/secretionIslets of Langerhans/drug effects/innervation/metabolism/secretionMaleMiceMice, Inbred C57BLMice, KnockoutMice, Mutant StrainsMolecular Targeted TherapyMyelin Proteins/antagonists & inhibitors/genetics/metabolismParasympathetic Nervous System/drug effectsTissue Culture TechniquesUp-Regulation/drug effects
PMID: 23274909
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Scléroses en plaques, neuroimmunologie, encéphalite autoimmune expérimentale (843)
Types cellulaires pancréatiques pendant l'ontogénèse (522)
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BONAL, Claire Brune et al. Nogo-A downregulation improves insulin secretion in mice. In: Diabetes, 2013, vol. 62, n° 5, p. 1443-52. doi: 10.2337/db12-0949 https://archive-ouverte.unige.ch/unige:32140

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Deposited on : 2013-12-16

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