Glomerular podocytes are a target for the actions of insulin. Accumulating evidence indicates that exposure to nutrient overload induces insulin resistance in these cells, manifested by abolition of the stimulatory effect of insulin on glucose uptake. Numerous recent studies have investigated potential mechanisms of the induction of insulin resistance in podocytes. High glucose concentrations stimulated reactive oxygen species production through NADPH oxidase activation, decreased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and reduced deacetylase sirtuin 1 (SIRT1) protein levels and activity. Calcium signaling involving transient receptor potential cation channel C, member 6 (TRPC6) also was demonstrated to play an essential role in the regulation of insulin-dependent signaling and glucose uptake in podocytes. Furthermore, podocytes exposed to diabetic environment, with elevated insulin levels become insulin resistant as a result of degradation of insulin receptor (IR), resulting in attenuation of insulin signaling responsiveness. Also elevated levels of palmitic acid appear to be an important factor and contributor to podocytes insulin resistance. This review summarizes cellular and molecular alterations that contribute to the development of insulin resistance in glomerular podocytes.

肾小球足细胞是胰岛素作用的目标。越来越多的证据表明，暴露于营养过剩会在这些细胞中诱导胰岛素抵抗，表现为胰岛素对葡萄糖摄取的刺激作用消失。许多最近的研究调查了在足细胞中诱导胰岛素抵抗的潜在机制。高葡萄糖浓度通过 NADPH 氧化酶激活刺激活性氧的产生，减少单磷酸腺苷活化蛋白激酶 (AMPK) 磷酸化，并降低脱乙酰酶 Sirtuin 1 (SIRT1) 蛋白水平和活性。钙信号涉及瞬时受体电位阳离子通道 C，成员 6 (TRPC6) 也被证明在足细胞中胰岛素依赖信号和葡萄糖摄取的调节中起重要作用。此外，暴露于糖尿病环境中的足细胞由于胰岛素受体 (IR) 的降解而导致胰岛素水平升高，从而导致胰岛素信号反应减弱，从而产生胰岛素抵抗。此外，棕榈酸水平升高似乎是足细胞胰岛素抵抗的重要因素和促成因素。本综述总结了导致肾小球足细胞胰岛素抵抗发展的细胞和分子改变。