Effects of Gastric Bypass Surgery on Expression of Glucose Transporters and Fibrotic Biomarkers in Kidney of Diabetic Fatty Rats

Abstract Background Diabetic nephropathy is the leading cause of chronic kidney disease. Observational studies suggest Roux-en-Y Bypass (RYGB) reduces progression of diabetic nephropathy. Objectives To unravel the mechanisms by which RYGB is beneficial and protective for diabetic nephropathy. Setting Academic laboratories Methods Forty-eight Zucker Diabetic Fatty (ZDF) rats were randomized to RYGB, sham surgery (SHAM), or pair-fed (PF) groups. An oral glucose tolerance test was performed at 25 days post-intervention and kidneys were harvested at 30 days. Primary outcome measures included expression of key genes and proteins in the glucose transport, oxidative stress, inflammation and fibrosis pathways. Results Thirty days post-intervention, RYGB rats weighed 349±8 g, which was lower than SHAM (436±14 g, P Conclusions Improvement of hyperglycemia after RYGB may reduce the glucose load on the kidney leading to a downregulation of specific glucose transporters. RYGB surgery may also attenuate kidney fibrosis through the AMPK/ TGFβ pathway.