题名：Nogo-a downregulation improves insulin secretion in mice.
作者：BONAL CB; BARONNIER DE; POT C; BENKHOUCHA M; SCHWAB ME; LALIVE PH; HERRERA PL;
来源：Diabetes. 2013 May;62(5):1443-52. doi: 10.2337/db12-0949. Epub 2012 Dec 28. [ IF= 8.29 ] ]
摘要：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.