| First Author | Jiang Y | Year | 2014 |
| Journal | J Neuroinflammation | Volume | 11 |
| Pages | 137 | PubMed ID | 25138272 |
| Mgi Jnum | J:336958 | Mgi Id | MGI:6840617 |
| Doi | 10.1186/s12974-014-0137-z | Citation | Jiang Y, et al. (2014) Etanercept restores normal insulin signal transduction in beta2-adrenergic receptor knockout mice. J Neuroinflammation 11:137 |
| abstractText | BACKGROUND: Inhibition of TNFalpha protects the retina against diabetic-like changes in rodent models. The mechanism by which TNFalpha induces deleterious retinal changes is not known. Previously, we have shown that TNFalpha can inhibit normal insulin signal transduction, leading to increased apoptosis in both retinal endothelial cells (REC) and Muller cells. Additionally, beta2-adrenergic receptor knockout mice (beta2KO) have increased TNFalpha levels and decreased insulin receptor activity. In this study, we hypothesized that inhibition of TNFalpha in beta2KO mice would increase normal insulin signaling, leading to improved retinal function. METHODS: C57BL6 or beta2KO mice were left untreated or treated with etanercept (0.3 mg/kg subcutaneously, 3x a week) for 2 months. Electroretinogram analyses were done before treatment was initiated and after two months of treatment with etanercept on all mice. Western blot or ELISA analyses were done on whole retinal lysates from all four groups of mice for TNFalpha, suppressor of cytokine signaling 3 (SOCS3), insulin receptor, and apoptotic proteins. RESULTS: Etanercept significantly reduced TNFalpha levels in beta2KO mice, leading to increased insulin receptor phosphorylation on tyrosine 1150/1151. SOCS3 levels were increased in beta2KO mice, which were reduced after etanercept treatment. Pro-apoptotic proteins were reduced in etanercept-treated beta2KO mice. Etanercept improved ERG amplitudes in beta2KO mice. CONCLUSIONS: Inhibition of TNFalpha by etanercept protects the retina likely through reduced TNFalpha-mediated insulin resistance, leading to reduced apoptosis. |
