Header

UZH-Logo

Maintenance Infos

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 (2013). Nogo-A downregulation improves insulin secretion in mice. Diabetes, 62(5):1443-1452.

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.

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.

Statistics

Citations

2 citations in Web of Science®
2 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

52 downloads since deposited on 18 Dec 2013
18 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:10 May 2013
Deposited On:18 Dec 2013 14:13
Last Modified:10 Aug 2017 13:08
Publisher:American Diabetes Association
ISSN:0012-1797
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.2337/db12-0949
PubMed ID:23274909

Download

Preview Icon on Download
Preview
Content: Published Version
Filetype: PDF
Size: 1MB
View at publisher