title: Duodenal-jejunal bypass surgery up-regulates the expression of the hepatic insulin signaling proteins and the key regulatory enzymes of intestinal gluconeogenesis in diabetic Goto-Kakizaki rats.
abstract: BACKGROUND
  Duodenal-jejunal bypass (DJB), which is not routinely applied in metabolic surgery, is an effective surgical procedure in terms of type 2 diabetes mellitus resolution. However, the underlying mechanisms are still undefined. Our aim was to investigate the diabetic improvement by DJB and to explore the changes in hepatic insulin signaling proteins and regulatory enzymes of gluconeogenesis after DJB in a non-obese diabetic rat model.
  
  
  METHODS
  Sixteen adult male Goto-Kakizaki rats were randomly divided into DJB and sham-operated groups. The body weight, food intake, hormone levels, and glucose metabolism were measured. The levels of protein expression and phosphorylation of insulin receptor-beta (IR-β) and insulin receptor substrate 2 (IRS-2) were evaluated in the liver. We also detected the expression of key regulatory enzymes of gluconeogenesis [phosphoenoylpyruvate carboxykinase-1 (PCK1), glucose-6-phosphatase-alpha (G6Pase-α)] in small intestine and liver.
  
  
  RESULTS
  DJB induced significant diabetic improvement with higher postprandial glucagons-like peptide 1, peptide YY, and insulin levels, but without weight loss. The DJB group exhibited increased expression and phosphorylation of IR-β and IRS-2 in liver, up-regulated the expression of PCK1 and G6Pase-α in small intestine, and down-regulated the expression of these enzymes in liver.
  
  
  CONCLUSIONS
  DJB is effective in up-regulating the expression of the key proteins in the hepatic insulin signaling pathway and the key regulatory enzymes of intestinal gluconeogenesis and down-regulating the expression of the key regulatory enzymes of hepatic gluconeogenesis without weight loss. Our study helps to reveal the potential role of hepatic insulin signaling pathway and intestinal gluconeogenesis in ameliorating insulin resistance after metabolic surgery.
authors.affiliation: Department of General Surgery, Qilu Hospital of Shandong University, #107 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.forename: Kexin
authors.initials: K
authors.lastname: Wang
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Yan
authors.forename: Guangyong
authors.initials: G
authors.lastname: Zhang
authors.forename: Shaozhuang
authors.initials: S
authors.lastname: Liu
authors.forename: Fengjun
authors.initials: F
authors.lastname: Liu
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Hu
authors.forename: Sanyuan
authors.initials: S
authors.lastname: Hu
mesh_terms: D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000601:surgery*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000601:surgery*; D015536:Down-Regulation; D004386:Duodenum / Q000378:metabolism / Q000601:surgery*; D015390:Gastric Bypass / Q000379:methods*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005943:Gluconeogenesis; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D054795:Incretins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism / Q000601:surgery*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012074:Remission Induction / Q000379:methods; D015398:Signal Transduction; D015854:Up-Regulation; D015431:Weight Loss
chemical_list: D001786:Blood Glucose; C526297:IRS2 protein, human; D054795:Incretins; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D052216:Glucagon-Like Peptide 1; D005952:Glucose-6-Phosphatase; C521898:PCK1 protein, human; D010729:Phosphoenolpyruvate Carboxykinase (GTP)