title: Duodenal-Jejunal bypass improves glucose homeostasis in association with decreased proinflammatory response and activation of JNK in the liver and adipose tissue in a T2DM rat model.
abstract: BACKGROUND
  There is accumulating evidence that obesity leads to a proinflammatory state, which plays crucial roles in insulin resistance and development of type 2 diabetes mellitus (T2DM). Previous studies demonstrated that weight loss after bariatric surgery was accompanied by a suppression of the proinflammatory state. However, the effect of bariatric surgery on the proinflammatory state and associated signaling beyond weight loss is still elusive. The objective of this study was to investigate the effect of duodenal-jejunal bypass (DJB) on glucose homeostasis, the proinflammatory state and the involving signaling independently of weight loss.
  
  
  METHODS
  A high-fat diet and low-dose streptozotocin administration were used to induce T2DM in male Sprague-Dawley rats. The diabetic rats underwent DJB or sham surgery. The blood glucose, glucose tolerance and insulin resistance were determined to evaluate the glucose homeostasis. Serum insulin, GLP-1 and hsCRP were detected by ELISA. The gene expression of TNF-α, IL-6, IL-1β and MCP-1 in liver and fat was determined by quantitative real-time RT-PCR. The JNK activity and serine phosphorylation of IRS-1 in liver and adipose tissue were determined by Western blotting.
  
  
  RESULTS
  Compared to the S-DJB group, DJB induced significant and sustained glycemic control with improved insulin sensitivity and glucose tolerance independently of weight loss. DJB improved the proinflammatory state indicated by decreased circulating hsCRP and proinflammatory gene expression in the liver and adipose tissue. The JNK activity and serine phosphorylation of IRS-1 in liver and adipose tissue were significantly reduced after DJB.
  
  
  CONCLUSIONS
  DJB achieved a rapid and sustainable glycemic control independently of weight loss. The data indicated that the improved proinflammatory state and decreased JNK activity after DJB may contribute to the improved glucose homeostasis.
authors.affiliation: Department of General Surgery, Qilu Hospital of Shandong University, 107#, Wenhua Xi Road, Jinan, 250012, Shandong, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Hu
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Su
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Guangyong
authors.initials: G
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.forename: Haifeng
authors.initials: H
authors.lastname: Han
authors.forename: Shaozhuang
authors.initials: S
authors.lastname: Liu
authors.forename: Sanyuan
authors.initials: S
authors.lastname: Hu
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018932:Chemokine CCL2; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000601:surgery*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000601:surgery*; D004195:Disease Models, Animal; D004386:Duodenum / Q000601:surgery; D015390:Gastric Bypass / Q000379:methods*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D007378:Interleukins / Q000378:metabolism; D007583:Jejunum / Q000601:surgery; D008099:Liver / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015431:Weight Loss
chemical_list: D001786:Blood Glucose; D018932:Chemokine CCL2; D055504:Insulin Receptor Substrate Proteins; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D052216:Glucagon-Like Peptide 1
references.citation: Lancet. 1999 May 15;353(9165):1649-52
references.pmid: 10335783
references.citation: Am J Physiol Endocrinol Metab. 2011 May;300(5):E923-32
references.pmid: 21304061
references.citation: Front Endocrinol (Lausanne). 2013 Aug 08;4:93
references.pmid: 23964268
references.citation: Obes Surg. 2012 Jun;22(6):950-5
references.pmid: 22527592
references.citation: Ann Surg. 2012 Jul;256(1):72-8
references.pmid: 22664560
references.citation: Obes Surg. 2009 Jan;19(1):96-104
references.pmid: 18989728
references.citation: Diabetes Metab. 2003 Sep;29(4 Pt 2):6S9-18
references.pmid: 14502096
references.citation: Mediators Inflamm. 2010;2010:
references.pmid: 20936118
references.citation: Science. 2005 Jan 21;307(5708):373-5
references.pmid: 15662001
references.citation: Gastroenterology. 2010 Jun;138(7):2437-46, 2446.e1
references.pmid: 20226188
references.citation: J Clin Endocrinol Metab. 2005 Jan;90(1):316-22
references.pmid: 15507518
references.citation: Ann Surg. 2004 Sep;240(3):416-23; discussion 423-4
references.pmid: 15319713
references.citation: Nat Med. 2005 Feb;11(2):183-90
references.pmid: 15685173
references.citation: J Hepatol. 2011 Jun;54(6):1214-23
references.pmid: 21145820
references.citation: Ann Surg. 2012 Dec;256(6):1049-58
references.pmid: 23001083
references.citation: Science. 1996 Feb 2;271(5249):665-8
references.pmid: 8571133
references.citation: Liver Int. 2013 May;33(5):794-804
references.pmid: 23432843
references.citation: Nutrition. 2011 Jan;27(1):73-80
references.pmid: 21146129
references.citation: Surg Obes Relat Dis. 2011 Sep-Oct;7(5):618-24
references.pmid: 21546319
references.citation: Am J Physiol Gastrointest Liver Physiol. 2013 Apr 1;304(7):G635-45
references.pmid: 23370676
references.citation: Eur Surg Res. 1985;17(1):25-32
references.pmid: 3972002
references.citation: Ann Surg. 2013 Jul;258(1):89-97
references.pmid: 23478528
references.citation: Surg Obes Relat Dis. 2014 Jul-Aug;10(4):641-6
references.pmid: 24238729
references.citation: Ann Surg. 2004 Jan;239(1):1-11
references.pmid: 14685093
references.citation: Ann Surg. 2008 Jun;247(6):968-75
references.pmid: 18520224
references.citation: Int J Obes (Lond). 2005 Jul;29(7):766-71
references.pmid: 15917853
references.citation: Diabetes. 1994 Nov;43(11):1271-8
references.pmid: 7926300
references.citation: FASEB J. 2010 Aug;24(8):2596-611
references.pmid: 20371626
references.citation: Eur J Pharmacol. 2013 Aug 15;714(1-3):448-55
references.pmid: 23845213
references.citation: Diabetes Metab. 2013 Feb;39(1):27-33
references.pmid: 22559931
references.citation: J Biol Chem. 2002 Jan 11;277(2):1531-7
references.pmid: 11606564
references.citation: Obes Surg. 2013 Nov;23(11):1734-42
references.pmid: 23700236
references.citation: Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):1042-7
references.pmid: 12714437
references.citation: Metabolism. 2013 Mar;62(3):347-51
references.pmid: 23062489
references.citation: J Biol Chem. 2000 Mar 24;275(12):9047-54
references.pmid: 10722755
references.citation: Diabetes Res Clin Pract. 2011 Dec;94(3):311-21
references.pmid: 22079683
references.citation: Surg Endosc. 2012 Nov;26(11):3287-92
references.pmid: 22678172
references.citation: J Clin Endocrinol Metab. 2002 Nov;87(11):5098-103
references.pmid: 12414878
references.citation: Ann Surg. 2006 Nov;244(5):741-9
references.pmid: 17060767
references.citation: Int J Obes (Lond). 2009 Apr;33 Suppl 1:S33-40
references.pmid: 19363506
references.citation: JAMA. 2004 Oct 13;292(14):1724-37
references.pmid: 15479938
references.citation: Am J Med. 2009 Mar;122(3):248-256.e5
references.pmid: 19272486
references.citation: Chin Med J (Engl). 2012 Mar;125(5):912-9
references.pmid: 22490596
references.citation: Pharmacol Res. 2005 Oct;52(4):313-20
references.pmid: 15979893
references.citation: Eur J Clin Invest. 2006 Jun;36(6):395-401
references.pmid: 16684123
references.citation: Nat Med. 2012 Jun;18(6):950-5
references.pmid: 22610279
references.citation: Nature. 2002 Nov 21;420(6913):333-6
references.pmid: 12447443
references.citation: J Hepatol. 2009 Oct;51(4):765-77
references.pmid: 19664840
references.citation: Surgery. 2007 Jul;142(1):74-85
references.pmid: 17630003
references.citation: JAMA. 2001 Jul 18;286(3):327-34
references.pmid: 11466099
references.citation: Diabetologia. 2005 Jun;48(6):1038-50
references.pmid: 15864529
references.citation: Arterioscler Thromb Vasc Biol. 2011 Sep;31(9):2063-9
references.pmid: 21680898