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Journal of Gastrointestinal Surgery

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Open Access 01-06-2013 | Original Article

Mechanism of Roux-en-Y Gastric Bypass Treatment for Type 2 Diabetes in Rats

Authors: Hongwei Yu, Xiyan Zheng, Zongming Zhang

Published in: Journal of Gastrointestinal Surgery | Issue 6/2013

Abstract

Objectives

Roux-en-Y gastric bypass (RYGB) is a novel therapy for diabetes. We aimed to explore the therapeutic mechanism of RYGB.

Methods

After RYGB, animal models were established, and gene expression profile of islets was assessed. Additionally, gastrointestinal hormones were measured using enzyme-linked immunosorbent assays. Ca²⁺ was studied using confocal microscopy and patch-clamp technique. The morphology of islets and beta cells was observed using optical microscopy and electron microscopy.

Results

RYGB was an effective treatment in diabetic rats. Expression profiling data showed that RYGB produced a new metabolic environment and that gene expression changed to adapt to the new environment. The differential expression of genes associated with hormones, Ca²⁺ and cellular proliferation was closely related to RYGB and diabetes metabolism. Furthermore, the data verified that RYGB led to changes in hormone level and enhanced Ca²⁺ concentration changes and Ca²⁺ channel activity. Morphological data showed that RYGB induced the proliferation of islets and improved the function of beta cells.

Conclusions

RYGB promoted a new metabolic environment while triggering changes to adapt to the new environment. These changes promoted the cellular proliferation of islets and improved the function of beta cells. The quantity of beta cells increased, and their quality improved, ultimately leading to insulin secretion enhancement.

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Shaw JE, Sicree RA, Zimmet PZ (2010) Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87: 4–14PubMedCrossRef

Dixon JB, Zimmet P, Alberti KG, Mbanya JC, Rubino F. Bariatric surgery for diabetes: the international diabetes federation takes a position. J Diabetes 2011;3:261–264PubMedCrossRef

Clark NG, Costa F, Eckel R, Fonseca V, Gerstein HC, Grundy S, Nesto RW, Pignone MP, Plutzky J, Porte D, Redberg R, Stitzel KF, Stone NJ. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care 2007;30:162–172PubMedCrossRef

Obeid F, Falvo A, Dabideen H, Stocks J, Moore M, Wright M. Open Roux-en-Y gastric bypass in 925 patients without mortality. Am J Surg 2005;189:352–356PubMedCrossRef

Hubens G, Balliu L, Ruppert M, Gypen B, Van TT, Vaneerdeweg W. Roux-en-Y gastric bypass procedure performed with the da Vinci robot system: is it worth it? Surg Endosc 2008;22:1690–1696PubMedCrossRef

Gass M, Beglinger C, Peterli R. Metabolic surgery-principles and current concepts. Langenbecks Arch Surg 2011;396:949–972PubMedCrossRef

Laferrere B. Do we really know why diabetes remits after gastric bypass surgery? Endocrine 2011;40:162–167PubMedCrossRef

Alfonso T , Rami L, Naji A, William O. R. Is Roux-en-Y Gastric Bypass Surgery the Most Effective Treatment for Type 2 Diabetes Mellitus in Morbidly Obese Patients? J Gastrointest Surg 2005;9:1112–1118CrossRef

Dixon JB, Zimmet P, Alberti KG, Rubino F. Bariatric surgery: an IDF statement for obese Type 2 diabetes. Diabetic Med 2011;28:628–642PubMedCrossRef

10.

Ramos AC, Galvao MP, de Souza YM, Galvao M, Murakami AH, Silva AC, Canseco EG, Santamaria R, Zambrano TA. Laparoscopic duodenal-jejunal exclusion in the treatment of type 2 diabetes millitus in patients with BMI < 30 kg/m²(LBMI). Obes Surg 2009;19:307–312PubMedCrossRef

11.

Mistry SB, Omana JJ, Kini S. Rat models for bariatric surgery and surgery for type 2 diabetes mellitus. Obes Surg 2009;19:655–660PubMedCrossRef

12.

Goto Y, Kakizaki M, Masaki N. Production of spontaneous diabetic rats by repetition of selective breeding. Tohoku J Exp Med 1976;119: 85–90PubMedCrossRef

13.

Marion LV, Serena C, Michael RR, Nayyar I. Narrative Review: Effect of Bariatric Surgery on Type 2 Diabetes Mellitus. Ann Intern Med 2009;150:94–103CrossRef

14.

Rubino F, Gagner M, Gentileschi P. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg 2004;240 :236–242PubMedCrossRef

15.

Ashrafian H, Athanasiou T, Li JV, Bueter M, Ahmed K, Nagpal K, Holmes E, Darzi A, Bloom S R. Diabetes resolution and hyperinsulinaemia after metabolic Roux-en-Y gastric bypass. Obesity Reviews 2011;12:e257-e272PubMedCrossRef

16.

de Haan BJ, Faas MM, Spijker H, van Willigen JW, de Haan A, de Vos P. Factors influencing isolation of functional pancreatic rat islets. Pancreas 2004;29:e15-e22.PubMedCrossRef

17.

Al-Mashat HA, Kandru S, Liu RK, Behl Y, Desta T, Graves DT. Diabetes enhances mRNA levels of proapoptotic genes and caspase activity, which contribute to impaired healing. Diabetes 2006;55: 487–495PubMedCrossRef

18.

Teruel MN, Chen W, Persechini A, Meyer T. Differential codes for free Ca²⁺-calmodulin signals in nucleus and cytosol. Curr Biol 2000;10:86–94PubMedCrossRef

19.

Barg S, Galvanovskis J, Gopel SO, Rorsman P, Eliasson L. Tight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells. Diabetes 2000;49 :1500–1510PubMedCrossRef

20.

Zhang ZY, Pan LJ, Zhang ZM. Functional interactions among STIM1, Orail and TRPC1 on the activation of SOCs in HL-7702 cells. Amino acids 2010;39:195–204PubMedCrossRef

21.

Butler AE, Janson J, Soeller WC, Butler PC. Increased-cell apoptosis prevents adaptive increase in-cell mass in mouse model of Type 2 Diabetes evidence for role of islet amyloid formation rather than direct action of amyloid . Diabetes 2003;52:2304–2314PubMedCrossRef

22.

Wagner J, Keizer J. Effects of rapid buffers on Ca²⁺ diffusion and Ca²⁺ oscillation. Biophys J 1994;67:447–456PubMedCrossRef

23.

Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G. Gene Ontology: tool for the unification of biology. Nat Genet 2000;25:25–29PubMedCrossRef

24.

Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signaling. Nat Rev Mol Cell Biol 2000;1:11–21.PubMedCrossRef

25.

Bootman MD, Collins TJ, Peppiatt CM, Prothero LS, MacKenzie L, De Smet P, Travers M, Tovey SC, Seo JT, Berridge MJ, Ciccolini F, Lipp P. Calcium signalling: an overview. Semin Cell Dev Biol 2001;12 :3–10PubMedCrossRef

26.

Pories WJ, Albrecht RJ. Etiology of type II diabetes mellitus: role of the foregut. World J Surg 2001;25:527–531PubMedCrossRef

27.

Zhang JV,Ren PG,Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, Hsueh AJW. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science 2005;310:996–999PubMedCrossRef

28.

Ikeda Y, Suehiro T, Nakamura T, Kumon Y, Hashimoto K. Clinical significance of the insulin resistance index as assessed by homeostasis model assessment. Endocr J 2001;48:81–86PubMedCrossRef

29.

Ukkola O. Gastric bypass and glucose metabolism. Intern Med J 2009;39:502–505PubMedCrossRef

30.

Thaler JP, Cummings DE. Hormonal and metabolic mechanisms of diabetes remission after gastrointestinal surgery. Endocrinology 2009;150:2518–2525PubMedCrossRef

31.

Engstrom BE, Burman P, Holdstock C, Karlsson FA. Effects of growth hormone (GH) on ghrelin, leptin, and adiponectin in GH-deficient patients. J Clin Endocrinol Metab 2003;88 :5193–5198CrossRef

32.

Kojima M, Hosoda H, Date Y, Tonon MC, Chartrel N, Cortes CL. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656–660PubMedCrossRef

33.

Meijer RI, van Wagensveld BA, Siegert CE, Eringa EC, Serne EH, Smulders YM. Bariatric surgery as a novel treatment for Type 2 Diabetes Mellitus. Arch Surg 2011;146: 744–750.PubMedCrossRef

34.

José MR, Silvia S, Xenia C, Sonia P, Albert G, David B, Lourdes T, Manuel P, Luis G. Effect of Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy on Glucose and Gut Hormones: a Prospective Randomised Trial. J Gastrointest Surg 2012;16:1116– 1122CrossRef

35.

De Block CE, Van Gaal LF. GLP-1 receptor agonists for type 2 diabetes. Lancet 2009;374 :4–6.PubMedCrossRef

36.

Rutter GA, Tsuboi T, Ravier MA. Ca²⁺ microdomains and the control of insulin secretion . Cell Calcium 2006;40:539–551PubMedCrossRef

37.

Hao MM, Li X, Rizzo MA, Rocheleau JV, Dawant BM, Piston DW. Regulation of two insulin granule populations within the reserve pool by distinct calcium sources. J Cell Sci 2005;118:5873–5884.PubMedCrossRef

38.

Scheenen WJ, Wollheim CB, Pozzan T, Fasolato C. Ca²⁺ depletion from granules inhibits exocytosis. A study with insulin-secreting cells. J Biol Chem 1998;273: 19002–19008.PubMedCrossRef

39.

Worley JF, McIntyre MS, Spencer B, Mertz RJ, Roe MW, Dukes ID. Endoplasmic reticulum calcium store regulates membrane potential in mouse islet beta-cells. J Biol Chem 1994;269:14359–14362PubMed

40.

Min Zhang, Goforth P, Bertram R, Sherman A, Satin L. The Ca²⁺ dynamics of isolated mouse β-cells and islets: implications for mathematical models. Biophys J 2003;84: 2852–2870PubMedCrossRef

Title: Mechanism of Roux-en-Y Gastric Bypass Treatment for Type 2 Diabetes in Rats
Authors: Hongwei Yu
Xiyan Zheng
Zongming Zhang
Publication date: 01-06-2013
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 6/2013
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-013-2188-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Mechanism of Roux-en-Y Gastric Bypass Treatment for Type 2 Diabetes in Rats

Abstract

Objectives

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Methods

Results

Conclusions

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