| First Author | Bonal CB | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 5 | Pages | 1443-52 |
| PubMed ID | 23274909 | Mgi Jnum | J:208581 |
| Mgi Id | MGI:5563731 | Doi | 10.2337/db12-0949 |
| Citation | Bonal CB, et al. (2013) Nogo-A downregulation improves insulin secretion in mice. Diabetes 62(5):1443-52 |
| abstractText | Type 2 diabetes (T2D) is characterized by beta-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 beta-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 beta-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. |
