Andreea Oana Mocanu1,2, Anny Mulya3, Hazel Huang3, Olivia Dan4, Philip R Schauer4, Anca Dinischiotu1, Stacy A Brethauer4, John P Kirwan5,6,7. 1. Biochemistry Department, Faculty of Biology, University of Bucharest, Bucharest, Romania. 2. Metabolic Translational Research Center, Cleveland Clinic, Cleveland, OH, USA. 3. Department of Pathobiology, Cleveland Clinic, Cleveland, OH, USA. 4. Bariatric Metabolic Institute, Cleveland Clinic, Cleveland, OH, USA. 5. Metabolic Translational Research Center, Cleveland Clinic, Cleveland, OH, USA. kirwanj@ccf.org. 6. Department of Pathobiology, Cleveland Clinic, Cleveland, OH, USA. kirwanj@ccf.org. 7. Department of Gastroenterology & Hepatology, Cleveland Clinic, Cleveland, OH, USA. kirwanj@ccf.org.
Abstract
PURPOSE: Diabetes and obesity are associated with inflammasome-mediated low-grade, chronic inflammation that may induce pancreatic beta-cell dysfunction and apoptosis. We examined the effects of Roux-en-Y gastric bypass (RYGB) surgery on NOD-like receptor family, pyrin domain containing-3 (NLRP3) inflammasome-related genes from pancreatic islets of Zucker diabetic fatty rats. MATERIALS AND METHODS: Islets were collected from Zucker diabetic fatty sham control and RYGB, 30 days after surgery. We assessed expression of genes that regulate glucose metabolism and the NLRP3 inflammasome (NLRP3, caspase-1, IL-1β, IL-18, apoptosis-associated speck-like protein), IL-6, and monocyte chemoattractant protein-1. RESULTS: Gene expression for NLRP3 (p < 0.02), IL-1β (p < 0.04), and IL-6 (p < 0.01) was reduced by RYGB and positively correlated with change in body weight. IL-1β positively correlated with glucose AUC response. CONCLUSION: Suppression of the NLRP3 inflammasome in pancreatic islets may contribute to improved glycemic control after RYGB.
PURPOSE:Diabetes and obesity are associated with inflammasome-mediated low-grade, chronic inflammation that may induce pancreatic beta-cell dysfunction and apoptosis. We examined the effects of Roux-en-Y gastric bypass (RYGB) surgery on NOD-like receptor family, pyrin domain containing-3 (NLRP3) inflammasome-related genes from pancreatic islets of Zucker diabetic fatty rats. MATERIALS AND METHODS: Islets were collected from Zucker diabetic fatty sham control and RYGB, 30 days after surgery. We assessed expression of genes that regulate glucose metabolism and the NLRP3 inflammasome (NLRP3, caspase-1, IL-1β, IL-18, apoptosis-associated speck-like protein), IL-6, and monocyte chemoattractant protein-1. RESULTS: Gene expression for NLRP3 (p < 0.02), IL-1β (p < 0.04), and IL-6 (p < 0.01) was reduced by RYGB and positively correlated with change in body weight. IL-1β positively correlated with glucose AUC response. CONCLUSION: Suppression of the NLRP3 inflammasome in pancreatic islets may contribute to improved glycemic control after RYGB.
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Authors: Philip R Schauer; Deepak L Bhatt; John P Kirwan; Kathy Wolski; Stacy A Brethauer; Sankar D Navaneethan; Ali Aminian; Claire E Pothier; Esther S H Kim; Steven E Nissen; Sangeeta R Kashyap Journal: N Engl J Med Date: 2014-03-31 Impact factor: 91.245
Authors: Michael M Meguid; Eduardo J B Ramos; Susumu Suzuki; Yuan Xu; Zachariah M George; Undurti N Das; Karen Hughes; Robert Quinn; Chung Chen; William Marx; Paul R G Cunningham Journal: J Gastrointest Surg Date: 2004 Jul-Aug Impact factor: 3.452
Authors: Bolormaa Vandanmagsar; Yun-Hee Youm; Anthony Ravussin; Jose E Galgani; Krisztian Stadler; Randall L Mynatt; Eric Ravussin; Jacqueline M Stephens; Vishwa Deep Dixit Journal: Nat Med Date: 2011-01-09 Impact factor: 53.440
Authors: Andreea Oana Mocanu; Anny Mulya; Hazel Huang; Olivia Dan; Hideharu Shimizu; Esam Batayyah; Stacy A Brethauer; Anca Dinischiotu; John P Kirwan Journal: PLoS One Date: 2015-10-05 Impact factor: 3.240