title: Roux-en-Y Gastric Bypass Surgery Suppresses Hepatic Gluconeogenesis and Increases Intestinal Gluconeogenesis in a T2DM Rat Model.
abstract: Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the effects of RYGB on glucose homeostasis, lipid metabolism, and intestinal morphological adaption, as well as hepatic and intestinal gluconeogenesis.
  
  
  
  Twenty adult male T2DM rats induced by high-fat diet and low dose of streptozotocin were randomly divided into sham and RYGB groups. The parameters of body weight, food intake, glucose tolerance, insulin sensitivity, and serum lipid profiles were assessed to evaluate metabolic changes. Intestinal sections were stained with hematoxylin and eosin (H&E) for light microscopy examination. The messenger RNA (mRNA) and protein expression levels of key regulatory enzymes of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase)] were determined through reverse-transcription PCR (RT-PCR) and Western blotting, respectively.
  
  
  
  RYGB induced significant improvements in glucose tolerance and insulin sensitivity, along with weight loss and decreased food intake. RYGB also decreased serum triglyceride (TG) and free fatty acid (FFA) levels. The jejunum and ileum exhibited a marked increase in the length and number of intestinal villi after RYGB. The RYGB group exhibited downregulated mRNA and protein expression levels of PEPCK and G6Pase in the liver and upregulated expression of these enzymes in the jejunum and ileum tissues.
  
  
  
  RYGB ameliorates glucose and lipid metabolism accompanied by weight loss and calorie restriction. The small intestine shows hyperplasia and hypertrophy after RYGB. Meanwhile, our study demonstrated that the reduced hepatic gluconeogenesis and increased intestinal gluconeogenesis may contribute to improved glucose homeostasis after RYGB.
authors.affiliation: Department of General Surgery, Central Hospital of Fengxian District, Southern Medical University, No.6600, Nan Feng Road, Shanghai, 201499, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Central Hospital of Fengxian District, Southern Medical University, No.6600, Nan Feng Road, Shanghai, 201499, China.
authors.forename: Fanzhi
authors.initials: F
authors.lastname: Kong
authors.affiliation: Department of General Surgery, Central Hospital of Fengxian District, Southern Medical University, No.6600, Nan Feng Road, Shanghai, 201499, China.
authors.forename: Suibin
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Central Hospital of Fengxian District, Southern Medical University, No.6600, Nan Feng Road, Shanghai, 201499, China.
authors.forename: Xuzhong
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Sha
authors.affiliation: Department of General Surgery, Central Hospital of Fengxian District, Southern Medical University, No.6600, Nan Feng Road, Shanghai, 201499, China.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Central Hospital of Fengxian District, Southern Medical University, No.6600, Nan Feng Road, Shanghai, 201499, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Central Hospital of Fengxian District, Southern Medical University, No.6600, Nan Feng Road, Shanghai, 201499, China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Central Hospital of Fengxian District, Southern Medical University, No.6600, Nan Feng Road, Shanghai, 201499, China.
authors.forename: Shiguang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. alfredhc@sjtu.edu.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of General Surgery, Central Hospital of Fengxian District, Southern Medical University, No.6600, Nan Feng Road, Shanghai, 201499, China. lejing1996@aliyun.com.
authors.forename: Xueli
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology / Q000601:surgery*; D004195:Disease Models, Animal; D015390:Gastric Bypass; D005943:Gluconeogenesis / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000473:pathology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D009767:Obesity, Morbid / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005947:Glucose
keywords: Bariatric surgery; Gluconeogenesis; Glucose homeostasis; High-fat diet; Lipid profiles; Morphological adaption; Roux-en-Y gastric bypass; Streptozotocin; Type 2 diabetes mellitus