Dysfunctional insulin signalling is a causative factor in type-2 diabetes. While insulin signal transduction has been well investigated in many tissues, less is known in retinal tissues. We have previously reported that toll-like receptor 4 (TLR4) is involved in retinal damage in diabetes. We used TLR4 retinal Müller cell-specific knockout mice and Müller cells in culture to investigate the effects of loss of TLR4 on Müller cell insulin signal transduction. Loss of TLR4 in the mouse retinal Müller cells led to increased insulin receptor and Akt phosphorylation, with reduced insulin receptor substrate 1 (IRS-1) phosphorylation on serine 307, which was associated with reduced cleavage of caspase 3. In retinal Müller cells grown in high glucose, insulin signal transduction was impaired, but these responses were reduced with cells were transfected with TLR4 siRNA. Taken together, the data suggest that TLR4 regulates insulin signal transduction in retinal Müller cells.

功能障碍的胰岛素信号传导是2型糖尿病的病因。尽管已经在许多组织中对胰岛素信号转导进行了深入研究，但在视网膜组织中知之甚少。我们先前曾报道过，toll​​样受体4（TLR4）与糖尿病视网膜损害有关。我们使用TLR4视网膜Müller细胞特异性基因敲除小鼠和Müller细胞进行培养，以研究TLR4缺失对Müller细胞胰岛素信号转导的影响。小鼠视网膜Müller细胞中TLR4的缺失导致胰岛素受体和Akt磷酸化增强，丝氨酸307上的胰岛素受体底物1（IRS-1）磷酸化降低，这与胱天蛋白酶3的裂解减少有关。高血糖，胰岛素信号转导受损，但是，用TLR4 siRNA转染的细胞可降低这些反应。两者合计，数据表明TLR4调节视网膜Müller细胞中的胰岛素信号转导。