Wei 2020 Cell Rep

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Wei X, Lu Z, Li L, Zhang H, Sun F, Ma H, Wang L, Hu Y, Yan Z, Zheng H, Yang G, Liu D, Tepel M, Gao P, Zhu Z (2020) Reducing NADPH synthesis counteracts diabetic nephropathy through restoration of AMPK activity in type 1 diabetic rats. Cell Rep 32:108207.

» PMID: 32997989 Open Access

Wei Xiao, Lu Zongshi, Li Li, Zhang Hexuan, Sun Fang, Ma Huan, Wang Lijuan, Hu Yingru, Yan Zhencheng, Zheng Hongting, Yang Gangyi, Liu Daoyan, Tepel Martin, Gao Peng, Zhu Zhiming (2020) Cell Rep

Abstract: Diabetic nephropathy (DN) is a major complication of diabetes mellitus and a primary cause of end-stage renal failure. Clinical studies indicate that metabolic surgery improves DN; however, the mechanism remains unclear. Here, we report that Roux-en-Y Gastric Bypass (RYGB) surgery significantly blocked and reversed DN without affecting the insulin signaling pathway. This protective role of RYGB surgery is almost blocked by either inhibition or knockout of 5'AMP-activated protein kinase (AMPK) in podocytes. Furthermore, mRNA microarray data reveal that RYGB surgery obviously reduced the gene expression involved in nicotinamide adenine dinucleotide phosphate (NAPDH) synthesis. The expression of a key NADPH synthase, hexose-6-phosphate dehydrogenase (H6PD), was inhibited by the low plasma corticosterone level after surgery. In addition, blocking NAPDH synthesis by knocking down H6PD mimicked the beneficial role of RYGB surgery through activation of AMPK in podocytes. Therefore, this study demonstrates that reducing NADPH production is critical for renal AMPK activation in response to RYGB surgery.

Keywords: AMPK, NADPH, RYGB surgery, Diabetic nephropathy, Podocyte Bioblast editor: Plangger M O2k-Network Lab: CN Chongqing Zhu Z


Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Diabetes 

Organism: Rat  Tissue;cell: Kidney  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k 

2020-10