Reducing NADPH Synthesis Counteracts Diabetic Nephropathy through Restoration of AMPK Activity in Type 1 Diabetic Rats

• DOI: 10.1016/j.celrep.2020.108207
• Publication Date: 2020-09-29T14:37:52Z
• Authors: Xiao Wei; Zongshi Lu; Li Li; Hexuan Zhang; Fang Sun; Huan Ma; Lijuan Wang; Yingru Hu; Zhencheng Yan; Hongting Zheng; Gangyi Yang; Daoyan Liu; Martin Tepel; Peng Gao; Zhiming Zhu
• Keywords: Gastric bypass surgery; AMP-Activated Protein Kinase

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