糖尿病肾病
医学
胰岛素抵抗
脂质代谢
内科学
肾病
内分泌学
糖尿病
他汀类
药理学
炎症
脂毒性
作者
Tongsheng Huang,Teng Wu,Yandi Wu,Xinghui Li,Jing Tan,Conghui Shen,Shi-jie Xiong,Zi-qi Feng,Saifei Gao,Hui Li,Weibin Cai
标识
DOI:10.1038/s41467-023-35944-z
摘要
Statins play an important role in the treatment of diabetic nephropathy. Increasing attention has been given to the relationship between statins and insulin resistance, but many randomized controlled trials confirm that the therapeutic effects of statins on diabetic nephropathy are more beneficial than harmful. However, further confirmation of whether the beneficial effects of chronic statin administration on diabetic nephropathy outweigh the detrimental effects is urgently needed. Here, we find that long-term statin administration may increase insulin resistance, interfere with lipid metabolism, leads to inflammation and fibrosis, and ultimately fuel diabetic nephropathy progression in diabetic mice. Mechanistically, activation of insulin-regulated phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway leads to increased fatty acid synthesis. Furthermore, statins administration increases lipid uptake and inhibits fatty acid oxidation, leading to lipid deposition. Here we show that long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice.
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