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However, there is limited knowledge on tissue-specific hormone distribution post-RYGB surgery and how this compares with best medical treatment (BMT). In the present study, pancreatic and ileal tissues were excised from male Zucker-Diabetic Sprague Dawley (ZDSD) rats 8-weeks after RYGB, BMT (daily oral dosing with metformin 300mg\/kg, fenofibrate 100mg\/kg, ramipril 1mg\/kg, rosuvastatin 10mg\/kg and subcutaneous liraglutide 0.2mg\/kg) or sham operation (laparotomy). Insulin, glucagon, somatostatin, PYY, GLP-1 and GIP expression patterns were assessed using immunocytochemistry and analyzed using ImageJ. After RYGB and BMT, body weight and plasma glucose were decreased. Intestinal morphometry was unaltered by RYGB, but crypt depth was decreased by BMT. Intestinal PYY cells were increased by both interventions. GLP-1- and GIP-cell counts were unchanged by RYGB but BMT increased ileal GLP-1-cells and decreased those expressing GIP. The intestinal contents of PYY and GLP-1 were significantly enhanced by RYGB, whereas BMT decreased ileal GLP-1. No changes of islet and beta-cell area or proliferation were observed, but the extent of beta-cell apoptosis and islet integrity calculated using circularity index were improved by both treatments. Significantly decreased islet alpha-cell areas were observed in both groups, while beta- and PYY-cell areas were unchanged. RYGB also induced a decrease in islet delta-cell area. PYY and GLP-1 colocalization with glucagon in islets was significantly decreased in both groups, while co-staining of PYY with glucagon was decreased and that with somatostatin increased. These data characterize significant cellular islet and intestinal adaptations following RYGB and BMT associated with amelioration of obesity-diabetes in ZDSD rats. The differential responses observed and particularly those within islets, may provide important clues to the unique ability of RYGB to cause diabetes remission.<\/jats:p>","DOI":"10.1371\/journal.pone.0274788","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T17:59:44Z","timestamp":1663869584000},"page":"e0274788","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Differential effects of RYGB surgery and best medical treatment for obesity-diabetes on intestinal and islet adaptations in obese-diabetic ZDSD rats"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3865-5067","authenticated-orcid":true,"given":"Ananyaa","family":"Sridhar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-1821","authenticated-orcid":true,"given":"Dawood","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Abdelaal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie A.","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violetta","family":"Naughton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Flatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5521-5445","authenticated-orcid":true,"given":"Carel W.","family":"Le Roux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil G.","family":"Docherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7196-7863","authenticated-orcid":true,"given":"Charlotte R.","family":"Moffett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"pone.0274788.ref001","first-page":"705","article-title":"The prevention and treatment of obesity","volume":"111","author":"A Wirth","year":"2014","journal-title":"Deutsches \u00c4rzteblatt International"},{"key":"pone.0274788.ref002","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.soard.2020.03.009","article-title":"Selecting surgical procedures for medically uncontrolled type 2 diabetes","volume":"16","author":"R. 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Vella","year":"2014","journal-title":"Physiology"},{"key":"pone.0274788.ref031","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1007\/s11695-015-1882-5","article-title":"Gastric bypass-related effects on glucose control, \u03b2 cell function and morphology in the obese zucker rat","volume":"26","author":"F Seyfried","year":"2016","journal-title":"Obesity Surg"},{"key":"pone.0274788.ref032","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1530\/JOE-14-0701","article-title":"Pancreatic hyperplasia after gastric bypass surgery in a GK rat model of non-obese type 2 diabetes","volume":"228","author":"X Zhou","year":"2016","journal-title":"J Endocrinol"},{"key":"pone.0274788.ref033","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1080\/19382014.2018.1513748","article-title":"Evidence of unrestrained beta-cell proliferation and neogenesis in a patient with hyperinsulinemic hypoglycemia after gastric bypass surgery","volume":"10","author":"N Dadheech","year":"2018","journal-title":"Islets"},{"key":"pone.0274788.ref034","doi-asserted-by":"crossref","first-page":"170445","DOI":"10.1016\/j.peptides.2020.170445","article-title":"GK-rats respond to gastric bypass surgery with improved glycemia despite unaffected insulin secretion and beta cell mass","volume":"136","author":"MG Miskelly","year":"2021","journal-title":"Peptides"},{"key":"pone.0274788.ref035","article-title":"Roux-en-Y Gastric Bypass Restores Islet Function and Morphology Independent of Body Weight in ZDF Rats","author":"JD Mosinski","year":"2021","journal-title":"American Journal of Physiology-Endocrinology and Metabolism"},{"key":"pone.0274788.ref036","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1210\/jc.2007-2851","article-title":"Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes","volume":"93","author":"B Laferr\u00e8re","year":"2008","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"pone.0274788.ref037","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.2337\/db11-0203","article-title":"Gastric bypass surgery enhances glucagon-like peptide 1\u2013stimulated postprandial insulin secretion in humans","volume":"60","author":"M Salehi","year":"2011","journal-title":"Diabetes"},{"key":"pone.0274788.ref038","first-page":"2227","article-title":"Changes in glucose homeostasis after Roux-en-Y gastric bypass surgery for obesity at day three, two months, and one year after surgery: role of gut peptides. The Journal of Clinical Endocrinology &","volume":"96","author":"Y Falk\u00e9n","year":"2011","journal-title":"Metabolism"},{"key":"pone.0274788.ref039","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.2337\/db13-0022","article-title":"Exaggerated glucagon-like peptide 1 response is important for improved \u03b2-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes","volume":"62","author":"NB J\u00f8rgensen","year":"2013","journal-title":"Diabetes"},{"key":"pone.0274788.ref040","doi-asserted-by":"crossref","first-page":"E122","DOI":"10.1152\/ajpendo.00073.2012","article-title":"Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance","volume":"303","author":"NB J\u00f8rgensen","year":"2012","journal-title":"American Journal of Physiology-Endocrinology and Metabolism"},{"key":"pone.0274788.ref041","doi-asserted-by":"crossref","first-page":"e101005","DOI":"10.1371\/journal.pone.0101005","article-title":"Role of endogenous GLP-1 and GIP in beta cell compensatory responses to insulin resistance and cellular stress","volume":"9","author":"S Vasu","year":"2014","journal-title":"PLoS One"},{"key":"pone.0274788.ref042","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.molmet.2013.11.010","article-title":"Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagon-like peptide-1 deficiency","volume":"3","author":"M Mokadem","year":"2014","journal-title":"Molecular metabolism"},{"key":"pone.0274788.ref043","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.2337\/dc06-1549","article-title":"Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes","volume":"30","author":"B Laferr\u00e8re","year":"2007","journal-title":"Diabetes Care"},{"key":"pone.0274788.ref044","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1007\/s11695-010-0305-x","article-title":"GIP and bariatric surgery","volume":"21","author":"RS Rao","year":"2011","journal-title":"Obesity Surg"},{"key":"pone.0274788.ref045","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1007\/s00464-012-2166-y","article-title":"Comparable early changes in gastrointestinal hormones after sleeve gastrectomy and Roux-En-Y gastric bypass surgery for morbidly obese type 2 diabetic subjects","volume":"26","author":"F Romero","year":"2012","journal-title":"Surg Endosc"},{"key":"pone.0274788.ref046","first-page":"1936","article-title":"Medications Activating Tubular Fatty Acid Oxidation Enhance the Protective Effects of Roux-en-Y Gastric Bypass Surgery in a Rat Model of Early Diabetic Kidney Disease","author":"WP Martin","year":"2022","journal-title":"Frontiers in endocrinology"},{"key":"pone.0274788.ref047","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.bbagen.2017.01.005","article-title":"Influence of neuropeptide Y and pancreatic polypeptide on islet function and beta-cell survival","volume":"1861","author":"D Khan","year":"2017","journal-title":"Biochimica et Biophysica Acta (BBA)-General Subjects"},{"key":"pone.0274788.ref048","article-title":"Improvement of Glucose Metabolism following rapid weight loss after Bariatric Surgery and its impact on reduction of Visceral Abdominal Fat vs. Free Fat Muscle","author":"VJ Cogollo","year":"2021","journal-title":"Surgery for Obesity and Related Diseases"},{"key":"pone.0274788.ref049","article-title":"Recent advances in the mechanisms underlying the beneficial effects of bariatric and metabolic surgery","author":"G Xu","year":"2020","journal-title":"Surgery for Obesity and Related Diseases"},{"key":"pone.0274788.ref050","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1007\/s11695-010-0113-3","article-title":"Metabolic surgery for the treatment of type 2 diabetes in patients with BMI< 35 kg\/m 2: an integrative review of early studies","volume":"20","author":"M Fried","year":"2010","journal-title":"Obesity Surg"},{"key":"pone.0274788.ref051","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.2337\/dc12-1596","article-title":"Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: analysis of a randomized control trial comparing surgery with intensive medical treatment","volume":"36","author":"SR Kashyap","year":"2013","journal-title":"Diabetes Care"},{"key":"pone.0274788.ref052","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s11695-015-1730-7","article-title":"Comparing the effectiveness of total gastrectomy and gastric bypass on glucose metabolism in diabetic rats","volume":"26","author":"D Zhou","year":"2016","journal-title":"Obesity Surg"},{"key":"pone.0274788.ref053","first-page":"2151","article-title":"Increased \u03b2-cell mass in obese rats after gastric bypass: a potential mechanism for improving glycemic control. Medical Science Monitor","volume":"23","author":"S Zhang","year":"2017","journal-title":"International Medical Journal of Experimental and Clinical Research"},{"key":"pone.0274788.ref054","doi-asserted-by":"crossref","first-page":"e52922","DOI":"10.1371\/journal.pone.0052922","article-title":"Development and verification of a mouse model for Roux-en-Y gastric bypass surgery with a small gastric pouch","volume":"8","author":"Z Hao","year":"2013","journal-title":"PloS one"},{"key":"pone.0274788.ref055","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1210\/en.2011-2041","article-title":"Resting energy expenditure and energetic cost of feeding are augmented after Roux-en-Y gastric bypass in obese mice","volume":"153","author":"E Nestoridi","year":"2012","journal-title":"Endocrinology"},{"key":"pone.0274788.ref056","first-page":"1","article-title":"Role of Gastrointestinal Hormones as a Predictive Factor for Long-Term Diabetes Remission: Randomized Trial Comparing Metabolic 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benefits of glucagon\u2010like peptide\u20101 (GLP\u20101) receptor ligands","volume":"179","author":"N Tanday","year":"2022","journal-title":"Br J Pharmacol"},{"key":"pone.0274788.ref069","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1677\/JOE-06-0148","article-title":"Protection of pancreatic \u03b2-cells by exendin-4 may involve the reduction of endoplasmic reticulum stress; in vivo and in vitro studies","volume":"193","author":"S Tsunekawa","year":"2007","journal-title":"J Endocrinol"},{"key":"pone.0274788.ref070","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1210\/endo.142.5.8128","article-title":"Glucagon-like peptide-1 causes pancreatic duodenal homeobox-1 protein translocation from the cytoplasm to the nucleus of pancreatic \u03b2-cells by a cyclic adenosine monophosphate\/protein kinase A-dependent mechanism","volume":"142","author":"X Wang","year":"2001","journal-title":"Endocrinology"},{"key":"pone.0274788.ref071","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1530\/JOE-19-0451","article-title":"Liraglutide and sitagliptin counter beta-to alpha-cell trans differentiation in diabetes","volume":"245","author":"N Tanday","year":"2020","journal-title":"J Endocrinol"},{"key":"pone.0274788.ref072","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.2337\/dc06-0392","article-title":"Hyperinsulinemic hypoglycemia after gastric bypass surgery is not accompanied by islet hyperplasia or increased \u03b2-cell turnover","volume":"29","author":"JJ Meier","year":"2006","journal-title":"Diabetes Care"},{"key":"pone.0274788.ref073","doi-asserted-by":"crossref","first-page":"151855","DOI":"10.1016\/j.aanat.2021.151855","article-title":"The long-term failure of RYGB surgery in improving T2DM is related to hyperinsulinism","volume":"240","author":"G P\u00e9rez-Arana","year":"2022","journal-title":"Annals of Anatomy-Anatomischer Anzeiger"},{"key":"pone.0274788.ref074","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s40618-021-01620-6","article-title":"Effects of first-line diabetes therapy with biguanides, sulphonylurea and thiazolidinediones on the differentiation, proliferation and apoptosis of islet cell populations","volume":"45","author":"D Sarnobat","year":"2022","journal-title":"J Endocrinol Invest"},{"key":"pone.0274788.ref075","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ebiom.2019.01.034","article-title":"Does PYY mediate resolution of diabetes following bariatric surgery?","volume":"40","author":"PK Chelikani","year":"2019","journal-title":"EBioMedicine"},{"key":"pone.0274788.ref076","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s11695-019-04239-y","article-title":"The leading role of peptide tyrosine tyrosine in glycemic control after Roux-en-Y gastric bypass in rats","volume":"30","author":"A Camacho-Ram\u00edrez","year":"2020","journal-title":"Obesity Surg"},{"key":"pone.0274788.ref077","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ebiom.2018.12.040","article-title":"PYY plays a key role in the resolution of diabetes following bariatric surgery in humans","volume":"40","author":"C Guida","year":"2019","journal-title":"EBioMedicine"},{"key":"pone.0274788.ref078","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1152\/physrev.00031.2014","article-title":"CCK, GLP-1, and PYY (3\u201336): secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB (vol 97, pg 411, 2017)","volume":"97","author":"RE Steinert","year":"2017","journal-title":"Physiol Rev"},{"key":"pone.0274788.ref079","article-title":"Established and emerging roles peptide YY (PYY) and exploitation in obesity-diabetes","author":"RA Lafferty","year":"2020","journal-title":"Current Opinion in Endocrinology, Diabetes, and Obesity"},{"key":"pone.0274788.ref080","article-title":"PYY, a Therapeutic Option for Type 2 Diabetes?","volume":"13","author":"C Guida","year":"2020","journal-title":"Clinical Medicine Insights: Endocrinology and Diabetes"},{"key":"pone.0274788.ref081","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1097\/00006676-198906000-00002","article-title":"Peptide YY: intrapancreatic localization and effects on insulin and glucagon secretion in the mouse","volume":"4","author":"G B\u00f6ttcher","year":"1989","journal-title":"Pancreas"},{"key":"pone.0274788.ref082","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1073\/pnas.74.5.2140","article-title":"Pancreatic immunoreactive somatostatin release","volume":"74","author":"GS Patton","year":"1977","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"pone.0274788.ref083","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1113\/JP274581","article-title":"\u03b4\u2010cells and \u03b2\u2010cells are electrically coupled and regulate \u03b1\u2010cell activity via somatostatin","volume":"596","author":"L Briant","year":"2018","journal-title":"J Physiol (Lond)"},{"key":"pone.0274788.ref084","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00109-020-01887-x","article-title":"Paracrine signaling in islet function and survival","volume":"98","author":"SM Hartig","year":"2020","journal-title":"Journal of Molecular Medicine"},{"key":"pone.0274788.ref085","first-page":"1","article-title":"Ablation of somatostatin cells leads to impaired pancreatic islet function and neonatal death in rodents","volume":"9","author":"N Li","year":"2018","journal-title":"Cell death & disease"},{"key":"pone.0274788.ref086","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1073\/pnas.0237106100","article-title":"Lower blood glucose, hyperglucagonemia, and pancreatic \u03b1 cell hyperplasia in glucagon receptor knockout mice","volume":"100","author":"RW Gelling","year":"2003","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"pone.0274788.ref087","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1111\/dom.13113","article-title":"Sitagliptin and Roux\u2010en\u2010Y gastric bypass modulate insulin secretion via regulation of intra\u2010islet PYY","volume":"20","author":"C Guida","year":"2018","journal-title":"Diabetes, Obesity and Metabolism"},{"key":"pone.0274788.ref088","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/ijo.2015.162","article-title":"Effects of RYGB on energy expenditure, appetite and glycaemic control: a randomized controlled clinical trial","volume":"40","author":"JB Schmidt","year":"2016","journal-title":"Int J Obes"},{"key":"pone.0274788.ref089","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1007\/s11695-014-1316-9","article-title":"Effects of meal size on the release of GLP-1 and PYY after Roux-en-Y gastric bypass surgery in obese subjects with or without type 2 diabetes","volume":"24","author":"W Yan","year":"2014","journal-title":"Obesity Surg"},{"key":"pone.0274788.ref090","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1002\/msj.20203","article-title":"Hormone changes affecting energy homeostasis after metabolic surgery","volume":"77","author":"EJ Harvey","year":"2010","journal-title":"Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine"},{"key":"pone.0274788.ref091","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1007\/s11695-012-0622-3","article-title":"Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial","volume":"22","author":"R Peterli","year":"2012","journal-title":"Obesity Surg"},{"key":"pone.0274788.ref092","doi-asserted-by":"crossref","first-page":"585","DOI":"10.3390\/nu11030585","article-title":"The PYY\/Y2R-deficient mouse responds normally to high-fat diet and gastric bypass surgery","volume":"11","author":"B Boland","year":"2019","journal-title":"Nutrients"},{"key":"pone.0274788.ref093","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3892\/ijmm.2015.2207","article-title":"Endogenous GLP-1 as a key self-defense molecule against lipotoxicity in pancreatic islets","volume":"36","author":"C Huang","year":"2015","journal-title":"Int J Mol Med"},{"key":"pone.0274788.ref094","doi-asserted-by":"crossref","first-page":"3262","DOI":"10.1007\/s00125-012-2716-9","article-title":"A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets","volume":"55","author":"P Marchetti","year":"2012","journal-title":"Diabetologia"},{"key":"pone.0274788.ref095","doi-asserted-by":"crossref","first-page":"101014","DOI":"10.1016\/j.molmet.2020.101014","article-title":"Human islets contain a subpopulation of glucagon-like peptide-1 secreting \u03b1 cells that is increased in type 2 diabetes","volume":"39","author":"SA Campbell","year":"2020","journal-title":"Molecular metabolism"},{"key":"pone.0274788.ref096","first-page":"4678","article-title":"Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal. The Journal of Clinical Endocrinology &","volume":"92","author":"AB Goldfine","year":"2007","journal-title":"Metabolism"},{"key":"pone.0274788.ref097","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-20301-1","article-title":"Bariatric surgery induces a new gastric mucosa phenotype with increased functional glucagon-like peptide-1 expressing cells","volume":"12","author":"L Ribeiro-Parenti","year":"2021","journal-title":"Nature communications"},{"key":"pone.0274788.ref098","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.3390\/nu10101529","article-title":"Effects of obesity and gastric bypass surgery on nutrient sensors, endocrine cells, and mucosal innervation of the mouse colon","volume":"10","author":"M Peiris","year":"2018","journal-title":"Nutrients"},{"key":"pone.0274788.ref099","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1365-3016.2009.01088.x","article-title":"Effects of calcium supplementation on fetal growth in mothers with deficient calcium intake: a randomised controlled trial","volume":"24","author":"E Abalos","year":"2010","journal-title":"Paediatr Perinat Epidemiol"},{"key":"pone.0274788.ref100","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1210\/jc.2010-0841","article-title":"Endogenous GLP-1 regulates postprandial glycemia in humans: relative contributions of insulin, glucagon, and gastric emptying","volume":"96","author":"M Nicolaus","year":"2011","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"pone.0274788.ref101","doi-asserted-by":"crossref","first-page":"R352","DOI":"10.1152\/ajpregu.00491.2013","article-title":"GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents","volume":"306","author":"J Ye","year":"2014","journal-title":"American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"},{"key":"pone.0274788.ref102","doi-asserted-by":"crossref","first-page":"e0134728","DOI":"10.1371\/journal.pone.0134728","article-title":"Gastric inhibitory polypeptide (GIP) is selectively decreased in the roux-limb of dietary obese mice after RYGB surgery","volume":"10","author":"J Zhou","year":"2015","journal-title":"Plos one"},{"key":"pone.0274788.ref103","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.2337\/db06-0068","article-title":"Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery","volume":"55","author":"C Guidone","year":"2006","journal-title":"Diabetes"},{"key":"pone.0274788.ref104","doi-asserted-by":"crossref","first-page":"E923","DOI":"10.1152\/ajpendo.00422.2010","article-title":"Duodenal-jejunal bypass protects GK rats from \u03b2-cell loss and aggravation of hyperglycemia and increases enteroendocrine cells coexpressing GIP and GLP-1","volume":"300","author":"M Speck","year":"2011","journal-title":"American Journal 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