Targeting Islets: Metabolic Surgery Is More than a Bariatric Surgery

  • Xi Chen
  • Jingjing Zhang
  • Zhiguang ZhouEmail author
Review Article


Metabolic surgery is an effective therapy for diabetic patients with obesity. The main mechanisms underlying the effects of metabolic surgery include food intake restriction and the accompanying reduced daily caloric intake and changes in gut hormones and bile acid. Insulin resistance and impaired β-cell function contribute to the development of type 2 diabetes. An increasing number of studies have focused on the central role of islet function in type 2 diabetes. In this article, we review the related high-quality literature and summarize the following mechanisms and principles underlying metabolic surgery in the context of islet function protection: (1) reduced glucotoxicity and chronic inflammation help facilitate better β-cell function and the preservation of β-cell mass following metabolic surgery; (2) based on the increased levels of GLP-1 and PYY after metabolic surgery, gut hormones appear to play a significant role in improving β-cell function through the GLP-1R signaling pathways; (3) the bile acid signaling pathway could affect β-cell function; and (4) the GLP-1R and bile acid signaling pathways could also cause other endocrine cells to contribute to islet function.


Metabolic surgery Islet function Obesity Type 2 diabetes mellitus Mechanisms 



International Diabetes Federation


Type 2 diabetes


Roux-en-Y gastric bypass


Sleeve gastrostomy


Bile acid


G protein-coupled receptors


Protein kinase C


Protein kinase A


Insulin receptor substrate-2


Protein kinase B


Transforming growth factor-β


Free fatty acid


Glucagon-like peptide 1




Gastric inhibitory polypeptide


Farnesoid X receptor


G protein-coupled bile acid receptor 5


Area under the curve


Fibroblast growth factor-19


GLP-1 receptor




Nuclear factor-κB



This study was supported by the National Key R&D Program of China (2016YFC1305000, 2016YFC1305001), the National Science and Technology Infrastructure Program (2015BAI12B13), the National Natural Science Foundation of China (81770775, 91749118, 81370017, 81130015, and 81000316), the Planned Science and Technology Project of Hunan Province (2017RS3015) and Natural Science Foundation of Hunan Province, China (14JJ3034), and the National Basic Research Program of China (2014CB910500).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval Statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent Statement

Does not apply.


  1. 1.
    Cho NH, Shaw JE, Karuranga S. IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271–81.CrossRefPubMedGoogle Scholar
  2. 2.
    Yang W, Lu J, Weng J. Prevalence of diabetes among men and women in China. N Engl J Med. 2010;362(12):1090–101.CrossRefPubMedGoogle Scholar
  3. 3.
    NCD-RisC NRFC. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet. 2016;387(10026):1377–96.CrossRefGoogle Scholar
  4. 4.
    Ramos-Levi AM, Rubio MA. Comment on Rubino et al. metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by International Diabetes Organizations. Diabetes Care 2016;39:861–877. Diabetes Care. 2017;40(7):e90–1.CrossRefPubMedGoogle Scholar
  5. 5.
    ADA. Standards of medical care in diabetes--2009. Diabetes Care. 2009;32 Suppl 1:S13–61.Google Scholar
  6. 6.
    Dixon JB, Zimmet P, Alberti KG. Bariatric surgery: an IDF statement for obese type 2 diabetes. Diabet Med. 2011;28(6):628–42.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Accili D. Lilly lecture 2003: the struggle for mastery in insulin action: from triumvirate to republic. Diabetes. 2004;53(7):1633–42.CrossRefPubMedGoogle Scholar
  8. 8.
    Chawla A, Nguyen KD, Goh YP. Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol. 2011;11(11):738–49.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov. 2014;13(6):465–76.CrossRefGoogle Scholar
  10. 10.
    Shu CJ, Benoist C, Mathis D. The immune system’s involvement in obesity-driven type 2 diabetes. Semin Immunol. 2012;24(6):436–42.CrossRefPubMedGoogle Scholar
  11. 11.
    Ferrannini E. Insulin resistance versus insulin deficiency in non-insulin-dependent diabetes mellitus: problems and prospects. Endocr Rev. 1998;19(4):477–90.CrossRefPubMedGoogle Scholar
  12. 12.
    Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11(2):98–107.CrossRefPubMedGoogle Scholar
  13. 13.
    Cerf ME. Beta cell dysfunction and insulin resistance. Front Endocrinol (Lausanne). 2013;4:37.CrossRefGoogle Scholar
  14. 14.
    Heit JJ, Karnik SK, Kim SK. Intrinsic regulators of pancreatic beta-cell proliferation. Annu Rev Cell Dev Biol. 2006;22:311–38.CrossRefPubMedGoogle Scholar
  15. 15.
    Vangoitsenhoven R, Mathieu C, Van der Schueren B. GLP1 and cancer: friend or foe? Endocr Relat Cancer. 2012;19(5):F77–88.CrossRefPubMedGoogle Scholar
  16. 16.
    Prentki M, Nolan CJ. Islet beta cell failure in type 2 diabetes. J Clin Invest. 2006;116(7):1802–12.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kalupahana NS, Moustaid-Moussa N, Claycombe KJ. Immunity as a link between obesity and insulin resistance. Mol Asp Med. 2012;33(1):26–34.CrossRefGoogle Scholar
  18. 18.
    Lee BC, Lee J. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochim Biophys Acta. 2014;1842(3):446–62.CrossRefPubMedGoogle Scholar
  19. 19.
    Butler PC, Meier JJ, Butler AE. The replication of beta cells in normal physiology, in disease and for therapy. Nat Clin Pract Endocrinol Metab. 2007;3(11):758–68.CrossRefPubMedGoogle Scholar
  20. 20.
    Talchai C, Lin HV, Kitamura T. Genetic and biochemical pathways of beta-cell failure in type 2 diabetes. Diabetes Obes Metab. 2009;11(Suppl 4):38–45.CrossRefPubMedGoogle Scholar
  21. 21.
    Merino B, Alonso-Magdalena P, Lluesma M. Pancreatic alpha-cells from female mice undergo morphofunctional changes during compensatory adaptations of the endocrine pancreas to diet-induced obesity. Sci Rep. 2015;5:11622.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Liu H, Javaheri A, Godar RJ. Intermittent fasting preserves beta-cell mass in obesity-induced diabetes via the autophagy-lysosome pathway. Autophagy. 2017;13(11):1952–68.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Tang C, Ahmed K, Gille A. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat Med. 2015;21(2):173–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Larsen CM, Faulenbach M, Vaag A. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356(15):1517–26.CrossRefPubMedGoogle Scholar
  25. 25.
    Bunck MC, Diamant M, Corner A. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care. 2009;32(5):762–8.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Xu W, Bi Y, Sun Z. Comparison of the effects on glycaemic control and beta-cell function in newly diagnosed type 2 diabetes patients of treatment with exenatide, insulin or pioglitazone: a multicentre randomized parallel-group trial (the CONFIDENCE study). J Intern Med. 2015;277(1):137–50.CrossRefPubMedGoogle Scholar
  27. 27.
    Yang Z, Zhou Z, Li X. Rosiglitazone preserves islet beta-cell function of adult-onset latent autoimmune diabetes in 3 years follow-up study. Diabetes Res Clin Pract. 2009;83(1):54–60.CrossRefPubMedGoogle Scholar
  28. 28.
    Zhao Y, Yang L, Xiang Y. Dipeptidyl peptidase 4 inhibitor sitagliptin maintains beta-cell function in patients with recent-onset latent autoimmune diabetes in adults: one year prospective study. J Clin Endocrinol Metab. 2014;99(5):E876–80.CrossRefPubMedGoogle Scholar
  29. 29.
    Yin YN, Yu QF, Fu N. Effects of four Bifidobacteria on obesity in high-fat diet induced rats. World J Gastroenterol. 2010;16(27):3394–401.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Karamanakos SN, Vagenas K, Kalfarentzos F. Weight loss, appetite suppression, and changes in fasting and postprandial ghrelin and peptide-YY levels after Roux-en-Y gastric bypass and sleeve gastrectomy: a prospective, double blind study. Ann Surg. 2008;247(3):401–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Peterli R, Wolnerhanssen B, Peters T. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial. Ann Surg. 2009;250(2):234–41.CrossRefPubMedGoogle Scholar
  32. 32.
    Peterli R, Borbely Y, Kern B. Early results of the Swiss Multicentre Bypass or Sleeve Study (SM-BOSS): a prospective randomized trial comparing laparoscopic sleeve gastrectomy and roux-en-Y gastric bypass. Ann Surg. 2013;258(5):690–694, 695.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Peterli R, Wolnerhanssen BK, Vetter D. Laparoscopic sleeve gastrectomy versus Roux-Y-gastric bypass for morbid obesity-3-year outcomes of the prospective randomized Swiss Multicenter Bypass or Sleeve Study (SM-BOSS). Ann Surg. 2017;265(3):466–73.CrossRefPubMedGoogle Scholar
  34. 34.
    Ochner CN, Gibson C, Shanik M. Changes in neurohormonal gut peptides following bariatric surgery. Int J Obes. 2011;35(2):153–66.CrossRefGoogle Scholar
  35. 35.
    Lee WJ, Chen CY, Chong K. Changes in postprandial gut hormones after metabolic surgery: a comparison of gastric bypass and sleeve gastrectomy. Surg Obes Relat Dis. 2011;7(6):683–90.CrossRefPubMedGoogle Scholar
  36. 36.
    Thaler JP, Cummings DE. Minireview: hormonal and metabolic mechanisms of diabetes remission after gastrointestinal surgery. Endocrinology. 2009;150(6):2518–25.CrossRefPubMedGoogle Scholar
  37. 37.
    Cummings DE, Weigle DS, Frayo RS. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002;346(21):1623–30.CrossRefPubMedGoogle Scholar
  38. 38.
    Holdstock C, Engstrom BE, Ohrvall M. Ghrelin and adipose tissue regulatory peptides: effect of gastric bypass surgery in obese humans. J Clin Endocrinol Metab. 2003;88(7):3177–83.CrossRefPubMedGoogle Scholar
  39. 39.
    Stoeckli R, Chanda R, Langer I. Changes of body weight and plasma ghrelin levels after gastric banding and gastric bypass. Obes Res. 2004;12(2):346–50.CrossRefPubMedGoogle Scholar
  40. 40.
    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(2):236–42.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Clements RH, Gonzalez QH, Long CI. Hormonal changes after Roux-en-Y gastric bypass for morbid obesity and the control of type-II diabetes mellitus. Am Surg. 2004;70(1):1–4. 4-5PubMedGoogle Scholar
  42. 42.
    DePaula AL, Macedo AL, Schraibman V. Hormonal evaluation following laparoscopic treatment of type 2 diabetes mellitus patients with BMI 20-34. Surg Endosc. 2009;23(8):1724–32.CrossRefPubMedGoogle Scholar
  43. 43.
    Farey JE, Preda TC, Fisher OM. Effect of laparoscopic sleeve gastrectomy on fasting gastrointestinal, pancreatic, and adipose-derived hormones and on non-esterified fatty acids. Obes Surg. 2017;27(2):399–407.CrossRefPubMedGoogle Scholar
  44. 44.
    Jahansouz C, Xu H, Hertzel AV. Bile acids increase independently from hypocaloric restriction after bariatric surgery. Ann Surg. 2016;264(6):1022–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Jorgensen NB, Dirksen C, Bojsen-Moller KN. Improvements in glucose metabolism early after gastric bypass surgery are not explained by increases in total bile acids and fibroblast growth factor 19 concentrations. J Clin Endocrinol Metab. 2015;100(3):E396–406.CrossRefPubMedGoogle Scholar
  46. 46.
    Khan FH, Shaw L, Zhang W. Fibroblast growth factor 21 correlates with weight loss after vertical sleeve gastrectomy in adolescents. Obesity (Silver Spring). 2016;24(11):2377–83.CrossRefGoogle Scholar
  47. 47.
    Steinert RE, Peterli R, Keller S. Bile acids and gut peptide secretion after bariatric surgery: a 1-year prospective randomized pilot trial. Obesity (Silver Spring). 2013;21(12):E660–8.CrossRefGoogle Scholar
  48. 48.
    Ryan KK, Tremaroli V, Clemmensen C. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature. 2014;509(7499):183–8.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Ding L, Sousa KM, Jin L. Vertical sleeve gastrectomy activates GPBAR-1/TGR5 to sustain weight loss, improve fatty liver, and remit insulin resistance in mice. Hepatology. 2016;64(3):760–73.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    McGavigan AK, Garibay D, Henseler ZM. TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice. Gut. 2017;66(2):226–34.CrossRefPubMedGoogle Scholar
  51. 51.
    Ley RE, Backhed F, Turnbaugh P. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005;102(31):11070–5.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Ley RE, Turnbaugh PJ, Klein S. Microbial ecology: Human gut microbes associated with obesity. Nature. 2006;444(7122):1022–3.CrossRefGoogle Scholar
  53. 53.
    Liou AP, Paziuk M, Luevano JJ. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5(178):141r–78r.CrossRefGoogle Scholar
  54. 54.
    Li JV, Ashrafian H, Bueter M. Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk. Gut. 2011;60(9):1214–23.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Zhang H, DiBaise JK, Zuccolo A. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A. 2009;106(7):2365–70.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Furet JP, Kong LC, Tap J. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59(12):3049–57.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Talchai C, Xuan S, Lin HV. Pancreatic beta cell dedifferentiation as a mechanism of diabetic beta cell failure. Cell. 2012;150(6):1223–34.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Taylor BL, Liu FF, Sander M. Nkx6.1 is essential for maintaining the functional state of pancreatic beta cells. Cell Rep. 2013;4(6):1262–75.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Puri S, Akiyama H, Hebrok M. VHL-mediated disruption of Sox9 activity compromises beta-cell identity and results in diabetes mellitus. Genes Dev. 2013;27(23):2563–75.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Guo S, Dai C, Guo M. Inactivation of specific beta cell transcription factors in type 2 diabetes. J Clin Invest. 2013;123(8):3305–16.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Wang Z, York NW, Nichols CG. Pancreatic beta cell dedifferentiation in diabetes and redifferentiation following insulin therapy. Cell Metab. 2014;19(5):872–82.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Cinti F, Bouchi R, Kim-Muller JY. Evidence of beta-cell dedifferentiation in human type 2 diabetes. J Clin Endocrinol Metab. 2016;101(3):1044–54.CrossRefPubMedGoogle Scholar
  63. 63.
    Savage PJ, Bennion LJ, Flock EV. Diet-induced improvement of abnormalities in insulin and glucagon secretion and in insulin receptor binding in diabetes mellitus. J Clin Endocrinol Metab. 1979;48(6):999–1007.CrossRefPubMedGoogle Scholar
  64. 64.
    Greenwood RH, Mahler RF, Hales CN. Improvement in insulin secretion in diabetes after diazoxide. Lancet. 1976;1(7957):444–7.CrossRefPubMedGoogle Scholar
  65. 65.
    Wajchenberg BL. Beta-cell failure in diabetes and preservation by clinical treatment. Endocr Rev. 2007;28(2):187–218.CrossRefPubMedGoogle Scholar
  66. 66.
    Zhou X, Qian B, Ji N. Pancreatic hyperplasia after gastric bypass surgery in a GK rat model of non-obese type 2 diabetes. J Endocrinol. 2016;228(1):13–23.CrossRefPubMedGoogle Scholar
  67. 67.
    Qian B, Zhou X, Li B. Reduction of pancreatic beta-cell dedifferentiation after gastric bypass surgery in diabetic rats. J Mol Cell Biol. 2014;6(6):531–4.CrossRefPubMedGoogle Scholar
  68. 68.
    Roslin MS, Dudiy Y, Weiskopf J. Comparison between RYGB, DS, and VSG effect on glucose homeostasis. Obes Surg. 2012;22(8):1281–6.CrossRefPubMedGoogle Scholar
  69. 69.
    Mari A, Manco M, Guidone C. Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function. Diabetologia. 2006;49(9):2136–43.CrossRefPubMedGoogle Scholar
  70. 70.
    Nannipieri M, Mari A, Anselmino M. 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(9):E1372–9.CrossRefPubMedGoogle Scholar
  71. 71.
    Chiellini C, Iaconelli A, Familiari P. Study of the effects of transoral gastroplasty on insulin sensitivity and secretion in obese subjects. Nutr Metab Cardiovasc Dis. 2010;20(3):202–7.CrossRefPubMedGoogle Scholar
  72. 72.
    Bosello O, Armellini F, Pelloso M. Glucose tolerance in jejunoileal bypass for morbid obesity: a fifteen month follow-up. Diabete Metab. 1978;4(3):159–62.PubMedGoogle Scholar
  73. 73.
    Sirinek KR, O’Dorisio TM, Hill D. Hyperinsulinism, glucose-dependent insulinotropic polypeptide, and the enteroinsular axis in morbidly obese patients before and after gastric bypass. Surgery. 1986;100(4):781–7.PubMedGoogle Scholar
  74. 74.
    Karayiannakis AJ, Syrigos KN, Zbar A. The effect of vertical banded gastroplasty on glucose-induced beta-endorphin response. J Surg Res. 1998;80(2):123–8.CrossRefPubMedGoogle Scholar
  75. 75.
    Kopp HP, Kopp CW, Festa A. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol. 2003;23(6):1042–7.CrossRefPubMedGoogle Scholar
  76. 76.
    Korner J, Inabnet W, Febres G. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes. 2009;33(7):786–95.CrossRefGoogle Scholar
  77. 77.
    de Carvalho CP, Marin DM, de Souza AL. GLP-1 and adiponectin: effect of weight loss after dietary restriction and gastric bypass in morbidly obese patients with normal and abnormal glucose metabolism. Obes Surg. 2009;19(3):313–20.CrossRefPubMedGoogle Scholar
  78. 78.
    De Paula AL, Stival AR, Halpern A. Improvement in insulin sensitivity and beta-cell function following ileal interposition with sleeve gastrectomy in type 2 diabetic patients: potential mechanisms. J Gastrointest Surg. 2011;15(8):1344–53.CrossRefPubMedGoogle Scholar
  79. 79.
    Lee WJ, Ser KH, Chong K. Laparoscopic sleeve gastrectomy for diabetes treatment in nonmorbidly obese patients: efficacy and change of insulin secretion. Surgery. 2010;147(5):664–9.CrossRefPubMedGoogle Scholar
  80. 80.
    Umeda LM, Silva EA, Carneiro G. Early improvement in glycemic control after bariatric surgery and its relationships with insulin, GLP-1, and glucagon secretion in type 2 diabetic patients. Obes Surg. 2011;21(7):896–901.CrossRefPubMedGoogle Scholar
  81. 81.
    Campos GM, Rabl C, Peeva S. Improvement in peripheral glucose uptake after gastric bypass surgery is observed only after substantial weight loss has occurred and correlates with the magnitude of weight lost. J Gastrointest Surg. 2010;14(1):15–23.CrossRefPubMedGoogle Scholar
  82. 82.
    Laferrere B, Heshka S, Wang K. Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes. Diabetes Care. 2007;30(7):1709–16.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Cummings DE, Cohen RV. Response to Comment on: Cohen et al. Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity. Diabetes Care 2012;35:1420–1428. Diabetes Care. 2013;36(4):e59.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Cummings DE. Metabolic surgery for type 2 diabetes. Nat Med. 2012;18(5):656–8.CrossRefPubMedGoogle Scholar
  85. 85.
    Ramracheya RD, McCulloch LJ, Clark A. PYY-dependent restoration of impaired insulin and glucagon secretion in type 2 diabetes following Roux-En-Y gastric bypass surgery. Cell Rep. 2016;15(5):944–50.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Alarcon C, Boland BB, Uchizono Y. Pancreatic beta-cell adaptive plasticity in obesity increases insulin production but adversely affects secretory function. Diabetes. 2016;65(2):438–50.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Martinussen C, Bojsen-Moller KN, Dirksen C. Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass. Am J Physiol Endocrinol Metab. 2015;308(6):E535–44.CrossRefPubMedGoogle Scholar
  88. 88.
    Ehses JA, Perren A, Eppler E. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes. 2007;56(9):2356–70.CrossRefPubMedGoogle Scholar
  89. 89.
    Richardson SJ, Willcox A, Bone AJ. Islet-associated macrophages in type 2 diabetes. Diabetologia. 2009;52(8):1686–8.CrossRefPubMedGoogle Scholar
  90. 90.
    Boni-Schnetzler M, Thorne J, Parnaud G. Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta -cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation. J Clin Endocrinol Metab. 2008;93(10):4065–74.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Eguchi K, Manabe I, Oishi-Tanaka Y. Saturated fatty acid and TLR signaling link beta cell dysfunction and islet inflammation. Cell Metab. 2012;15(4):518–33.CrossRefPubMedGoogle Scholar
  92. 92.
    Jones HB, Nugent D, Jenkins R. Variation in characteristics of islets of Langerhans in insulin-resistant, diabetic and non-diabetic-rat strains. Int J Exp Pathol. 2010;91(3):288–301.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Masters SL, Dunne A, Subramanian SL. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1beta in type 2 diabetes. Nat Immunol. 2010;11(10):897–904.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Youm YH, Adijiang A, Vandanmagsar B. Elimination of the NLRP3-ASC inflammasome protects against chronic obesity-induced pancreatic damage. Endocrinology. 2011;152(11):4039–45.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Nicol LE, Grant WF, Comstock SM. Pancreatic inflammation and increased islet macrophages in insulin-resistant juvenile primates. J Endocrinol. 2013;217(2):207–13.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Maedler K, Sergeev P, Ris F. Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest. 2017;127(4):1589.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Cancello R, Rouault C, Guilhem G. Urokinase plasminogen activator receptor in adipose tissue macrophages of morbidly obese subjects. Obes Facts. 2011;4(1):17–25.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Dillard TH, Purnell JQ, Smith MD. Omentectomy added to Roux-en-Y gastric bypass surgery: a randomized, controlled trial. Surg Obes Relat Dis. 2013;9(2):269–75.CrossRefPubMedGoogle Scholar
  99. 99.
    Moschen AR, Molnar C, Geiger S. Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor alpha expression. Gut. 2010;59(9):1259–64.CrossRefPubMedGoogle Scholar
  100. 100.
    Pardina E, Ferrer R, Baena-Fustegueras JA. Only C-reactive protein, but not TNF-alpha or IL6, reflects the improvement in inflammation after bariatric surgery. Obes Surg. 2012;22(1):131–9.CrossRefPubMedGoogle Scholar
  101. 101.
    Haider DG, Schindler K, Prager G. Serum retinol-binding protein 4 is reduced after weight loss in morbidly obese subjects. J Clin Endocrinol Metab. 2007;92(3):1168–71.CrossRefPubMedGoogle Scholar
  102. 102.
    Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131–57.CrossRefPubMedGoogle Scholar
  103. 103.
    Ye J, Hao Z, Mumphrey MB. GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents. Am J Physiol Regul Integr Comp Physiol. 2014;306(5):R352–62.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Wilson-Perez HE, Chambers AP, Ryan KK. 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
  105. 105.
    Bottcher G, Ahren B, Lundquist I. Peptide YY: intrapancreatic localization and effects on insulin and glucagon secretion in the mouse. Pancreas. 1989;4(3):282–8.CrossRefPubMedGoogle Scholar
  106. 106.
    Upchurch BH, Aponte GW, Leiter AB. Expression of peptide YY in all four islet cell types in the developing mouse pancreas suggests a common peptide YY-producing progenitor. Development. 1994;120(2):245–52.PubMedGoogle Scholar
  107. 107.
    Chandarana K, Batterham R. Curr Opin Endocrinol Diabetes Obes. 2008;15(1):65–72.CrossRefPubMedGoogle Scholar
  108. 108.
    Boey D, Sainsbury A, Herzog H. The role of peptide YY in regulating glucose homeostasis. Peptides. 2007;28(2):390–5.CrossRefPubMedGoogle Scholar
  109. 109.
    Sam AH, Gunner DJ, King A. Selective ablation of peptide YY cells in adult mice reveals their role in beta cell survival. Gastroenterology. 2012;143(2):459–68.CrossRefPubMedGoogle Scholar
  110. 110.
    Shi YC, Loh K, Bensellam M. Pancreatic PYY is critical in the control of insulin secretion and glucose homeostasis in female mice. Endocrinology. 2015;156(9):3122–36.CrossRefPubMedGoogle Scholar
  111. 111.
    Garibay D, Lou J, Lee SA. Beta cell GLP-1R signaling alters alpha cell proglucagon processing after vertical sleeve gastrectomy in mice. Cell Rep. 2018;23(4):967–73.CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Mokadem M, Zechner JF, Margolskee RF. Effects of Roux-en-Y gastric bypass on energy and glucose homeostasis are preserved in two mouse models of functional glucagon-like peptide-1 deficiency. Mol Metab. 2014;3(2):191–201.CrossRefPubMedGoogle Scholar
  113. 113.
    Sachdev S, Wang Q, Billington C. FGF 19 and bile acids increase following Roux-en-Y gastric bypass but not after medical management in patients with type 2 diabetes. Obes Surg. 2016;26(5):957–65.CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Nemati R, Lu J, Dokpuang D. Increased bile acids and FGF19 after sleeve gastrectomy and Roux-en-Y gastric bypass correlate with improvement in type 2 diabetes in a randomized trial. Obes Surg. 2018;28(9):2672–86.CrossRefPubMedGoogle Scholar
  115. 115.
    Kohli R, Kirby M, Setchell KD. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Am J Physiol Gastrointest Liver Physiol. 2010;299(3):G652–60.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Cariou B, van Harmelen K, Duran-Sandoval D. The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice. J Biol Chem. 2006;281(16):11039–49.CrossRefPubMedGoogle Scholar
  117. 117.
    Prawitt J, Abdelkarim M, Stroeve JH. Farnesoid X receptor deficiency improves glucose homeostasis in mouse models of obesity. Diabetes. 2011;60(7):1861–71.CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Morton GJ, Matsen ME, Bracy DP. FGF19 action in the brain induces insulin-independent glucose lowering. J Clin Invest. 2013;123(11):4799–808.CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Ryan KK, Kohli R, Gutierrez-Aguilar R. Fibroblast growth factor-19 action in the brain reduces food intake and body weight and improves glucose tolerance in male rats. Endocrinology. 2013;154(1):9–15.CrossRefPubMedGoogle Scholar
  120. 120.
    Baud G, Daoudi M, Hubert T. Bile diversion in Roux-en-Y gastric bypass modulates sodium-dependent glucose intestinal uptake. Cell Metab. 2016;23(3):547–53.CrossRefPubMedGoogle Scholar
  121. 121.
    Whalley NM, Pritchard LE, Smith DM. Processing of proglucagon to GLP-1 in pancreatic alpha-cells: is this a paracrine mechanism enabling GLP-1 to act on beta-cells? J Endocrinol. 2011;211(1):99–106.CrossRefPubMedGoogle Scholar
  122. 122.
    Kumar DP, Rajagopal S, Mahavadi S. Activation of transmembrane bile acid receptor TGR5 stimulates insulin secretion in pancreatic beta cells. Biochem Biophys Res Commun. 2012;427(3):600–5.CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Kumar DP, Asgharpour A, Mirshahi F. Activation of transmembrane bile acid receptor TGR5 modulates pancreatic islet alpha cells to promote glucose homeostasis. J Biol Chem. 2016;291(13):6626–40.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Metabolism and Endocrinology, The Second Xiangya Hospital and Diabetes Center, Institute of Metabolism and Endocrinology and National Clinical Research Center for Metabolic DiseasesCentral South UniversityChangshaChina
  2. 2.Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education; National Clinical Research Center for Metabolic Diseases; Metabolic Syndrome Research Center, the Second Xiangya HospitalCentral South UniversityChangshaChina

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