en
Scientific article
Open access
English

Nogo-A downregulation improves insulin secretion in mice

Published inDiabetes, vol. 62, no. 5, p. 1443-1452
Publication date2013
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
Citation (ISO format)
BONAL, Claire Brune et al. Nogo-A downregulation improves insulin secretion in mice. In: Diabetes, 2013, vol. 62, n° 5, p. 1443–1452. doi: 10.2337/db12-0949
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal0012-1797
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232downloads

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