title: Gastric Bypass-Related Effects on Glucose Control, β Cell Function and Morphology in the Obese Zucker Rat.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.affiliation: Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital of Wuerzburg, Oberduerrbacher Str. 6 97080, Wuerzburg, Germany. seyfried_f@ukw.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Seyfried
authors.affiliation: Department of Investigative Medicine, Imperial College London, London, UK.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Miras
authors.affiliation: Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital of Wuerzburg, Oberduerrbacher Str. 6 97080, Wuerzburg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Rotzinger
authors.affiliation: Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital of Wuerzburg, Oberduerrbacher Str. 6 97080, Wuerzburg, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Nordbeck
authors.affiliation: Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital of Wuerzburg, Oberduerrbacher Str. 6 97080, Wuerzburg, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Corteville
authors.affiliation: Division of Computational and Systems Medicine, Imperial College London, London, UK.|Centre for Digestive and Gut Health, Department of Surgery and Cancer, Institute of Global Health Innovation, Imperial College London, London, UK.
authors.forename: Jia V
authors.initials: JV
authors.lastname: Li
authors.affiliation: Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital of Wuerzburg, Oberduerrbacher Str. 6 97080, Wuerzburg, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schlegel
authors.affiliation: Department of Medicine, Integrated Research and Treatment Centre for Adiposity Diseases, University of Leipzig, Leipzig, Germany.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Hankir
authors.affiliation: Department of Medicine, Integrated Research and Treatment Centre for Adiposity Diseases, University of Leipzig, Leipzig, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Fenske
authors.affiliation: Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital of Wuerzburg, Oberduerrbacher Str. 6 97080, Wuerzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Otto
authors.affiliation: Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital of Wuerzburg, Oberduerrbacher Str. 6 97080, Wuerzburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Jurowich
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D031204:Caloric Restriction; D015390:Gastric Bypass / Q000379:methods*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D000067757:Glucagon-Like Peptide-1 Receptor / Q000096:biosynthesis / Q000235:genetics; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology; D006943:Hyperglycemia / Q000209:etiology; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008297:Male; D009767:Obesity, Morbid / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D019518:Postprandial Period; D012333:RNA, Messenger / Q000235:genetics; D011924:Rats, Zucker; D015431:Weight Loss / Q000502:physiology
chemical_list: D001786:Blood Glucose; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D012333:RNA, Messenger; D052216:Glucagon-Like Peptide 1
keywords: GLP-1; Gastric bypass; Islet morphology; Zucker rat; β cell function