GPR40 Activation Abolishes Diabetes-Induced Painful Neuropathy by Suppressing VEGF-A Expression

• DOI: 10.2337/figshare.18624830
• Publication Date: 2022-01-21T16:53:37Z
• Authors: Vanessa Königs; Sandra Pierre; Martin Schicht; Jessica Welss; Lisa Hahnefeld; Vittoria Rimola; Elke Lütjen-Drecoll; Gerd Geisslinger; Klaus Scholich
• Keywords: Vascular permeability

G-protein coupled receptor 40 (GPR40) is a promising target to support glucose-induced insulin release in patients with diabetes type 2. Here, we studied the role of GPR40 regulation blood-nerve-barrier integrity and its involvement diabetes-induced neuropathies. Since modulates release, used streptozotocin-model for 1 diabetes, since here functions can be investigated independently effects on release. Diabetic wildtype mice exhibited increased vascular endothelial permeability showed epineural microlesions sciatic nerves, which were also observed naïve GPR40<sup>-/-</sup> mice. Fittingly, expression VEGF-A, an inducer permeability, was diabetic GPR40<sup>-/- </sup>mice. antagonists VEGF-A murine human cells as well transendothelial barriers. In contrast agonists suppressed mRNA expression. The VEGF inhibitor Axitinib prevented hypersensitivities reduced permeability. Importantly, agonist GW9508 reverted established hypersensitivity, effect blocked by administration. Thus, activation suppresses thereby reducing reverting hypersensitivities.