Florian Seyfried1, Alexander D Miras2, Laura Rotzinger3, Arno Nordbeck3, Caroline Corteville3, Jia V Li4,5, Nicolas Schlegel3, Mohammed Hankir6, Wiebke Fenske6, Christoph Otto3, Christian Jurowich3. 1. Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital of Wuerzburg, Oberduerrbacher Str. 6 97080, Wuerzburg, Germany. seyfried_f@ukw.de. 2. Department of Investigative Medicine, Imperial College London, London, UK. 3. Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital of Wuerzburg, Oberduerrbacher Str. 6 97080, Wuerzburg, Germany. 4. Division of Computational and Systems Medicine, Imperial College London, London, UK. 5. Centre for Digestive and Gut Health, Department of Surgery and Cancer, Institute of Global Health Innovation, Imperial College London, London, UK. 6. Department of Medicine, Integrated Research and Treatment Centre for Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Abstract
BACKGROUND: Roux-en-Y gastric bypass (RYGB) may improve beta cell function by mechanisms other than caloric restriction and body weight loss. We aimed to assess the impact of anatomical and hormonal alterations specific to RYGB on glucose homeostasis, β cell function and morphology. METHODS: Male Zucker(fa/fa) rats underwent either RYGB (n = 11) or sham surgeries (n = 10). Five of the shams were then food restricted and body weight matched (BWM) to the RYGB rats. Six male Zucker(fa/+) rats underwent sham surgery and served as additional lean controls. Twenty-seven days after surgery, an oral glucose tolerance test (OGTT) was performed and plasma levels of glucose, insulin and glucagon-like peptide-1 (GLP-1) were measured. Immunohistological analysis of pancreatic islets was performed, and GLP-1 receptor and PDX-1 mRNA content were quantified. RESULTS: Shams consumed more food and gained more weight compared to both RYGB and BWM (p < 0.001). Hyperglycaemia was evident in ad libitum-fed shams, whilst postprandial glucose levels were lower in RYGB compared to the BWM sham group (p < 0.05). During the OGTT, RYGB rats responded with >2.5-fold increase of GLP-1. Histology revealed signs of islet degeneration in ad libitum-fed shams, but not in RYGB and sham BWM controls (p < 0.001). GLP-1 receptor and PDX-1 mRNA content was similar between the RYGB and BWM shams but higher compared to ad libitum shams (p < 0.05). CONCLUSIONS: Combined molecular, cellular and histological analyses of pancreatic function suggest that weight loss alone, and not the enhancement of GLP-1 responses, is predominant for the short-term β cell protective effects of RYGB.
BACKGROUND: Roux-en-Y gastric bypass (RYGB) may improve beta cell function by mechanisms other than caloric restriction and body weight loss. We aimed to assess the impact of anatomical and hormonal alterations specific to RYGB on glucose homeostasis, β cell function and morphology. METHODS: Male Zucker(fa/fa) rats underwent either RYGB (n = 11) or sham surgeries (n = 10). Five of the shams were then food restricted and body weight matched (BWM) to the RYGB rats. Six male Zucker(fa/+) rats underwent sham surgery and served as additional lean controls. Twenty-seven days after surgery, an oral glucose tolerance test (OGTT) was performed and plasma levels of glucose, insulin and glucagon-like peptide-1 (GLP-1) were measured. Immunohistological analysis of pancreatic islets was performed, and GLP-1 receptor and PDX-1 mRNA content were quantified. RESULTS: Shams consumed more food and gained more weight compared to both RYGB and BWM (p < 0.001). Hyperglycaemia was evident in ad libitum-fed shams, whilst postprandial glucose levels were lower in RYGB compared to the BWM sham group (p < 0.05). During the OGTT, RYGB rats responded with >2.5-fold increase of GLP-1. Histology revealed signs of islet degeneration in ad libitum-fed shams, but not in RYGB and sham BWM controls (p < 0.001). GLP-1 receptor and PDX-1 mRNA content was similar between the RYGB and BWM shams but higher compared to ad libitum shams (p < 0.05). CONCLUSIONS: Combined molecular, cellular and histological analyses of pancreatic function suggest that weight loss alone, and not the enhancement of GLP-1 responses, is predominant for the short-term β cell protective effects of RYGB.
Authors: David E Arterburn; Maren K Olsen; Valerie A Smith; Edward H Livingston; Lynn Van Scoyoc; William S Yancy; George Eid; Hollis Weidenbacher; Matthew L Maciejewski Journal: JAMA Date: 2015-01-06 Impact factor: 56.272
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: Jianping Ye; Zheng Hao; Michael B Mumphrey; R Leigh Townsend; Laurel M Patterson; Nicholas Stylopoulos; Heike Münzberg; Christopher D Morrison; Daniel J Drucker; Hans-Rudolf Berthoud Journal: Am J Physiol Regul Integr Comp Physiol Date: 2014-01-15 Impact factor: 3.619
Authors: Christian Ferdinand Jurowich; Prashanth Reddy Rikkala; Andreas Thalheimer; Christian Wichelmann; Florian Seyfried; Victor Sander; Michael Kreissl; Christoph-Thomas Germer; Hermann Koepsell; Christoph Otto Journal: Ann Surg Date: 2013-07 Impact factor: 12.969
Authors: Brian E Kadera; Kristian Lum; John Grant; Aurora D Pryor; Dana D Portenier; Eric J DeMaria Journal: Surg Obes Relat Dis Date: 2009-02-26 Impact factor: 4.734
Authors: Alexander D Miras; Florian Seyfried; Alkystis Phinikaridou; Marcelo E Andia; Ioannis Christakis; Alan C Spector; René M Botnar; Carel W le Roux Journal: Obes Facts Date: 2014-10-01 Impact factor: 3.942
Authors: Kirk M Habegger; Kristy M Heppner; Sarah E Amburgy; Nickki Ottaway; Jenna Holland; Christine Raver; Erin Bartley; Timo D Müller; Paul T Pfluger; Jose Berger; Mouhamadoul Toure; Stephen C Benoit; Richard D Dimarchi; Diego Perez-Tilve; David A D'Alessio; Randy J Seeley; Matthias H Tschöp Journal: Diabetes Date: 2013-11-01 Impact factor: 9.461
Authors: Mohammed K Hankir; Marianne Patt; Jörg T W Patt; Georg A Becker; Michael Rullmann; Mathias Kranz; Winnie Deuther-Conrad; Kristin Schischke; Florian Seyfried; Peter Brust; Swen Hesse; Osama Sabri; Ute Krügel; Wiebke K Fenske Journal: Front Neurosci Date: 2017-01-13 Impact factor: 4.677
Authors: Ulrich Dischinger; Julia Hasinger; Malina Königsrainer; Carolin Corteville; Christoph Otto; Martin Fassnacht; Mohamed Hankir; Florian Johannes David Seyfried Journal: Front Endocrinol (Lausanne) Date: 2021-01-22 Impact factor: 5.555
Authors: Ananyaa Sridhar; Dawood Khan; Mahmoud Abdelaal; Jessie A Elliott; Violetta Naughton; Peter R Flatt; Carel W Le Roux; Neil G Docherty; Charlotte R Moffett Journal: PLoS One Date: 2022-09-22 Impact factor: 3.752