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Effects of gastric bypass surgery on expression of glucose transporters and fibrotic biomarkers in kidney of diabetic fatty rats.
Metadata
Journalsurgery for obesity and related diseases3.812Date
2020 Apr 24
5 months ago
Type
Journal Article
Volume
2020-Sep / 16 : 1242-1248
Author
Vangoitsenhoven R 1, Mulya A 2, Mosinski JD 3, Brethauer SA 4, Schauer PR 5, Kirwan JP 6, Aminian A 7
Affiliation
  • 2. Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
  • 3. Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Gannon University, Erie, Pennsylvania.
  • 4. Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio.
  • 5. Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio; Pennington Biomedical Research Center, Baton Rouge, Louisiana.
  • 6. Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Pennington Biomedical Research Center, Baton Rouge, Louisiana.
  • 7. Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio. Electronic address: [email protected]
Doi
PMIDMESH
Abstract
BACKGROUND: Diabetic nephropathy is the leading cause of chronic kidney disease. Observational studies suggest Roux-en-Y gastric 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 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 < .001), but not PF (374 ± 18 g) rats. RYGB rats had lower fasting glucose than PF animals and improved homeostatic model assessment of insulin resistance compared with PF and SHAM groups. These enhanced metabolic outcomes were accompanied by reduced sodium-glucose co-transporter 1 (Sglt1) gene expression (-23% versus PF, P = .01) in the kidney of RYGB rats. Expression of Sglt2, Glut1, or Glut2 mRNA, or oxidative stress and inflammation markers did not differ significantly. However, RYGB surgery induced a 19% lower expression of transforming growth factor (Tgfβ) mRNA (P = .004) compared with SHAM treated animals. Notably, adenosine monophosphate-activated protein kinase phosphorylation was increased (P = .04) in kidneys of the RYGB surgery animals.
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 adenosine monophosphate-activated protein kinase/TGFβ pathway.
Keywords: Bariatric surgery Diabetes Diabetic nephropathy Gastric bypass RYGB Transforming growth factor Weight loss
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Surg Obes Relat Dissurgery for obesity and related diseases
Metadata
LocationUnited States
FromELSEVIER SCIENCE INC

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