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Obesity Surgery

, Volume 26, Issue 10, pp 2402–2410 | Cite as

Preventative Sleeve Gastrectomy Contributes to Maintaining β Cell Function in db/db Diabetic Mouse

  • Feng LiEmail author
  • Chunjun Sheng
  • Kexiu Song
  • Manna Zhang
  • Le Bu
  • Peng Yang
  • Hui Sheng
  • Hong Li
  • Shen QuEmail author
Original Contributions
  • 316 Downloads

Abstract

Background

We used the leptin-receptor (LPR)-deficient mice model (db/db), a spontaneous model of type 2 diabetes with early β cell dysfunction to determine whether a preventative sleeve gastrectomy (SG) is an effective technique for the treatment of β cell failure.

Methods

The animals operated at an early stage of life, prior to metabolic alterations, were used to study the molecular mechanisms of β cell function improvement after a SG.

Results

β cell function was significantly increased, and islet morphology remained normal, after the SG. The expression of Glut2, Pdx1, MafA, and Nkx6.1 were significantly increased after the SG. The expression of GLP-1 in the colonic tissue, as well as GLP-1R and PKC in islets, was significantly increased after the SG.

Conclusions

β cell dysfunction can be ameliorated by a preventative SG for db/db mice. Maintaining the GLP-1 pathway and key transcript factor (TF) activation contributes to the improvement of β cell function after a preventative SG.

Keywords

Sleeve gastrectomy Pancreatic β cell Islet Transcript factor GLP-1 

Notes

Compliance with Ethical Standards

All of the animal experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health.

Conflict of Interest

The authors declare no conflict of interest.

Statement of Animal Rights

All applicable institutional and/or national guidelines for the care and use of animals were followed.

Funding

This research is supported by grants from Shanghai Natural Science Foundation (14ZR1436600).

Disclosure Statement

The authors have nothing to disclose.

References

  1. 1.
    Tham JC, Howes N, le Roux CW. The role of bariatric surgery in the treatment of diabetes. Ther Adv Chronicle Dis. 2014;5(3):149–57.CrossRefGoogle Scholar
  2. 2.
    Rubino F, Gagner M, Gentileschi P, et al. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg. 2004;240:236–42.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Basso N, Capoccia D, Rizzello M, et al. First-phase insulin secretion, insulin sensitivity, ghrelin, GLP-1, and PYY changes 72 h after sleeve gastrectomy in obese diabetic patients: the gastric hypothesis. Surg Endosc. 2011;25:3540–50.CrossRefPubMedGoogle Scholar
  4. 4.
    Kashyap SR, Daud S, Kelly KR, et al. Acute effects of gastric bypass versus gastric restrictive surgery on beta-cell function and insulinotropic hormones in severely obese patients with type 2 diabetes. Int J Obes (Lond). 2010;34:462–71.CrossRefGoogle Scholar
  5. 5.
    Nannipieri M, Mari A, Anselmino M, et al. The role of beta-cell function and insulin sensitivity in the remission of type 2 diabetes after gastric bypass surgery. J Clin Endocrinol Metab. 2011;96:E1372–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Grong E, Kulseng B, Arbo IB, Nord C, Eriksson M, Ahlgren U, Mårvik R. Sleeve gastrectomy, but not duodenojejunostomy, preserves total beta-cell mass in Goto-Kakizaki rats evaluated by three-dimensional optical projection tomography. Surg Endosc. 2015 Jun 12.Google Scholar
  7. 7.
    Lee WJ, Almulaifi A, Tsou JJ, Ser KH, Lee YC, Chen SC. Laparoscopic sleeve gastrectomy for type 2 diabetes mellitus: predicting the success by ABCD score. Surg Obes Relat Dis. 2014 Dec 31.Google Scholar
  8. 8.
    Khorgami Z, Andalib A, Aminian A, Kroh MD, Schauer PR, Brethauer SA. Predictors of readmission after laparoscopic gastric bypass and sleeve gastrectomy: a comparative analysis of ACS-NSQIP database. Surg Endosc. 2015 Aug 26. [Epub ahead of print].Google Scholar
  9. 9.
    Brethauer SA, Aminian A, Romero-Talamás H, et al. Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus. Ann Surg. 2013;258(4):628–36. discussion 636–7.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Runkel M, Müller S, Brydniak R, et al. Downgrading of type 2 diabetes mellitus (T2DM) after obesity surgery: duration and severity matter. Obes Surg. 2015;25(3):494–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Casella G, Abbatini F, Calì B, et al. Ten-year duration of type 2 diabetes as prognostic factor for remission after sleeve gastrectomy. Surg Obes Relat Dis. 2011;7(6):697–702.CrossRefPubMedGoogle Scholar
  12. 12.
    Bruinsma BG, Uygun K, Yarmush ML, et al. Surgical models of Roux-en-Y gastric bypass surgery and sleeve gastrectomy in rats and mice. Nat Protoc. 2015;10(3):495–507.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Li F, Su Y, Cheng Y, et al. Conditional deletion of Men1 in the pancreatic β-cell leads to glucagon-expressing tumor development. Endocrinology. 2015;156(1):48–57.CrossRefPubMedGoogle Scholar
  14. 14.
    Guillam MT, Hümmler E, Schaerer E, et al. Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Nat Genet. 1997;17(3):327–30.CrossRefPubMedGoogle Scholar
  15. 15.
    Pan FC, Wright C. Pancreas organogenesis: from bud to plexus to gland. Dev Dyn. 2011;240(3):530–65.CrossRefPubMedGoogle Scholar
  16. 16.
    Wang H, Brun T, Kataoka K, et al. MAFA controls genes implicated in insulin biosynthesis and secretion. Diabetologia. 2007;50(2):348–58.CrossRefPubMedGoogle Scholar
  17. 17.
    Homo-Delarche F, Calderari S, Irminger JC, et al. Islet inflammation and fibrosis in a spontaneous model of type 2 diabetes, the GK rat. Diabetes. 2006;55(6):1625–33.CrossRefPubMedGoogle Scholar
  18. 18.
    Baetens D, Stefan Y, Ravazzola M, et al. Alteration of islet cell populations in spontaneously diabetic mice. Diabetes. 1978;27:1–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Kahn SE. Clinical review 135: the importance of beta-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab. 2001;86(9):4047–58.PubMedGoogle Scholar
  20. 20.
    Eickhoff H, Guimarães A, Louro TM, et al. Insulin resistance and beta cell function before and after sleeve gastrectomy in obese patients with impaired fasting glucose or type 2 diabetes. Surg Endosc. 2015;29(2):438–43.CrossRefPubMedGoogle Scholar
  21. 21.
    Mallipedhi A, Min T, Prior SL, et al. Association between the preoperative fasting and postprandial C-peptide AUC with resolution of type 2 diabetes 6 months following bariatric surgery. Metabolism. 2015;64(11):1556–63.CrossRefPubMedGoogle Scholar
  22. 22.
    Ramos-Leví AM, Matía P, Cabrerizo L, et al. C-peptide levels predict type 2 diabetes remission after bariatric surgery. Nutr Hosp. 2013;28(5):1599–603.PubMedGoogle Scholar
  23. 23.
    Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.CrossRefPubMedGoogle Scholar
  24. 24.
    Ahlgren U, Jonsson J, Jonsson L, et al. Specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the β-cell phenotype and maturity onset diabetes. Genes Dev. 1998;12(12):1763–8.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Reimer MK, Ahrén B. Altered beta-cell distribution of pdx1 and GLUT-2 after a short-term challenge with a high-fat diet in C57BL/6J mice. Diabetes. 2002;51 Suppl 1:S138–43.CrossRefPubMedGoogle Scholar
  26. 26.
    Waeber G, Thompson N, Nicod P, et al. Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. Mol Endocrinol. 1996;19:1327–34.Google Scholar
  27. 27.
    Aramata S, Han SI, Kataoka K. Roles and regulation of transcription factor MafA in islet B-cells. Endocr J. 2007;54:659–66.CrossRefPubMedGoogle Scholar
  28. 28.
    Raum JC, Gerrish K, Artner I, et al. FoxA2, Nkx2.2, and PDX-1 regulate islet beta-cell-specific mafA expression through conserved sequences located between base pairs −8118 and −7750 upstream from the transcription start site. Mol Cell Biol. 2006;26(15):5735–43.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Wang X, Cahill CM, Piñeyro MA, et al. Glucagon-like peptide-1 regulates the beta cell transcription factor, PDX-1, in insulinoma cells. Endocrinology. 1999;140(10):4904–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Jiménez A, Mari A, Casamitjana R, et al. GLP-1 and glucose tolerance after sleeve gastrectomy in morbidly obese subjects with type 2 diabetes. Diabetes. 2014;63(10):3372–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Wilson-Pérez HE, Chambers AP, Ryan KK, et al. Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like Peptide 1 receptor deficiency. Diabetes. 2013;62(7):2380–5.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Xu G, Kaneto H, Laybutt DR, et al. Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes. Diabetes. 2007;56(6):1551–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Feng Li
    • 1
    Email author
  • Chunjun Sheng
    • 1
  • Kexiu Song
    • 1
  • Manna Zhang
    • 1
  • Le Bu
    • 1
  • Peng Yang
    • 1
  • Hui Sheng
    • 1
  • Hong Li
    • 1
  • Shen Qu
    • 1
    Email author
  1. 1.Department of Endocrinology and Metabolism, Shanghai Tenth People’s HospitalTong-Ji UniversityShangHaiChina

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