IMMUNOHISTOCHEMICAL DETECTION OF L CELLS IN GASTROINTESTINAL TRACT MUCOSA OF PATIENTS AFTER SURGICAL TREATMENT FOR CONTROL OF TYPE 2 DIABETES MELLITUS

Priscila Costa Estabile, Mara Cristina de Almeida, Eduardo Bauml Campagnoli, Marco Aurelio Santo, Marcos Ricardo da Silva Rodrigues, Fábio Quirillo Milléo, Roberto Ferreira Artoni, Priscila Costa Estabile, Mara Cristina de Almeida, Eduardo Bauml Campagnoli, Marco Aurelio Santo, Marcos Ricardo da Silva Rodrigues, Fábio Quirillo Milléo, Roberto Ferreira Artoni

Abstract

Objective: Type 2 diabetes mellitus (T2DM) is a disease of global impact that has led to an increase in comorbidities and mortality in several countries. Immunoexpression of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (3-36) (PYY3-36) can be used as a scorer in the gastrointestinal tract to analyze L-cell activity in response to T2DM treatment. This study aimed to investigate the presence, location, and secretion of L cells in the small intestine of patients undergoing the form of bariatric surgery denominated adaptive gastroenteromentectomy with partial bipartition.

Methods: Immunohistochemical assays, quantitative real-time polymerase chain reaction (qPCR), and Western blot analysis were performed on samples of intestinal mucosa from patients with T2DM in both the preoperative and postoperative periods.

Results: All results were consistent and indicated basal expression and secretion of GLP-1 and PYY3-36 incretins by L cells. A greater density of cells was demonstrated in the most distal portions of the small intestine. No significant difference was found between GLP-1 and PYY3-36 expression levels in the preoperative and postoperative periods because of prolonged fasting during which the samples were collected.

Conclusion: The greater number of L cells in activity implies better peptide signaling, response, and functioning of the neuroendocrine system.

Conflict of interest statement

Conflict of interest: none

Figures

Figure 1 -. Immunolabeling using the (A)…
Figure 1 -. Immunolabeling using the (A) polyclonal antibody for peptide YY (3-36)and (B) monoclonal antibody for glucagon-like peptide-1. In both panels, note the absence of labeled immune L cells and a background in the region of the gastric fundus (a) and pylorus (b); few immune cells labeled in the region of the jejunum (c) and proximal ileum (d); and greater frequency of labeled active immune L cells in the most distal portions of the ileum (e; f). The paired Student’s t-test was used with the significance level set to 5% (p
Figure -2. mRNA expression levels of glucagon-like…
Figure -2. mRNA expression levels of glucagon-like peptide-1 from the ileum tissue in preoperative (pre) and postoperative (post) periods. Bands above the columns indicate gene expression verified by western blotting. The paired Student’s t-test was used with the significance level set to 5% (p
Figure 3 -. Immunolabeling using the monoclonal…
Figure 3 -. Immunolabeling using the monoclonal antibody for glucagon-like peptide-1. Note the increased number of labeled L cells in the postoperative period (b and d) compared to the preoperative period (a and c). The paired Student’s t-test was used with the significance level set to 5% (p
Figure 4 -. mRNA expression levels of…
Figure 4 -. mRNA expression levels of peptide YY (3-36) from the ileum tissue in preoperative (pre) and postoperative (post) periods. The paired Student’s t-test was used with the significance level set to 5% (p
Figure 5 -. Immunolabeling using the polyclonal…
Figure 5 -. Immunolabeling using the polyclonal antibody for peptide YY (3-36). Note the increased number of labeled L cells in the postoperative period (b and d) compared to the preoperative period (a and c). The paired Student’s t-test was used with the significance level set to 5% (p

References

    1. Addison ML, Minnion JS, Shillito JC, Suzuki K, Tan TM, Field BC, Germain-Zito N, Becker-Pauly C, Ghatei MA, Bloom SR, Murphy KG. A role for metalloendopeptidases in the breakdown of the gut hormone, PYY 3-36. Endocrinology. 2011;152(12):4630–4640. doi: 10.1210/en.2011-1195.
    1. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131–2157. doi: 10.1053/j.gastro.2007.03.054.
    1. Brubaker PL. Minireview: update on incretin biology: focus on glucagon-like peptide-1. Endocrinology. 2010;151(5):1984–1989. doi: 10.1210/en.2010-0115.
    1. Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, Bantle JP, Sledge I. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122(3):248–256.e5. doi: 10.1016/j.amjmed.2008.09.041.
    1. De-Cleva R, Cardia L, Vieira-Gadducci A, Greve JM, Santo MA. Lactate can be a marker of metabolic syndrome in severe obesity? Arq Bras Cir Dig. 2021;34(1):e1579. doi: 10.1590/0102-672020210001e1579.
    1. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368(9548):1696–1705. doi: 10.1016/S0140-6736(06)69705-5.
    1. Eissele R, Göke R, Willemer S, Harthus HP, Vermeer H, Arnold R, Göke B. Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest. 1992;22(4):283–291. doi: 10.1111/j.1365-2362.1992.tb01464.x.
    1. Elliott RM, Morgan LM, Tredger JA, Deacon S, Wright J, Marks V. Glucagon-like peptide-1 (7-36) amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns. J Endocrinol. 1993;138(1):159–166. doi: 10.1677/joe.0.1380159.
    1. Gomes MB, Giannella D, Neto, Ed Mendonça, Tambascia MA, Fonseca RM, Réa RR, Macedo G, Modesto J, Filho, Schmid H, Bittencourt AV, et al. Prevalência de sobrepeso e obesidade em pacientes com diabetes mellitus do tipo 2 no Brasil: estudo multicêntrico nacional [Nationwide multicenter study on the prevalence of overweight and obesity in type 2 diabetes mellitus in the Brazilian population] Arq Bras Endocrinol Metabol. 2006;50(1):136–144. doi: 10.1590/s0004-27302006000100019.
    1. Goran MI, Ulijaszek SJ, Ventura EE. Glob Public Health. 1. Vol. 8. 10.1080/17441692.2012.736257: 2013. High fructose corn syrup and diabetes prevalence: a global perspective; pp. 55–64.
    1. Guedes TP, Martins S, Costa M, Pereira SS, Morais T, Santos A, Nora M, Monteiro MP. Detailed characterization of incretin cell distribution along the human small intestine. Surg Obes Relat Dis. 2015;11(6):1323–1331. doi: 10.1016/j.soard.2015.02.011.
    1. Hutch CR, Sandoval D. The Role of GLP-1 in the Metabolic Success of Bariatric Surgery. Endocrinology. 2017;158(12):4139–4151. doi: 10.1210/en.2017-00564.
    1. Jorsal T, Rhee NA, Pedersen J, Wahlgren CD, Mortensen B, Jepsen SL, Jelsing J, Dalbøge LS, Vilmann P, Hassan H, et al. Enteroendocrine K and L cells in healthy and type 2 diabetic individuals. Diabetologia. 2018;61(2):284–294. doi: 10.1007/s00125-017-4450-9.
    1. Korner J, Bessler M, Cirilo LJ, Conwell IM, Daud A, Restuccia NL, Wardlaw SL. Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin. J Clin Endocrinol Metab. 2005;90(1):359–365. doi: 10.1210/jc.2004-1076.
    1. Laurie L., Baggio LL, Drucker DJ. Biology of Incretins: GLP-1 and GIP. Gastroenterology. 2007;(132):2131–2157. doi: 10.1053/j.gastro.2007.03.054.
    1. le Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F, Prasad V, Shurey S, Ghatei MA, Patel AG, Bloom SR. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006;243(1):108–114. doi: 10.1097/01.sla.0000183349.16877.84.
    1. Lundberg JM, Tatemoto K, Terenius L, Hellström PM, Mutt V, Hökfelt T, Hamberger B. Localization of peptide YY (PYY) in gastrointestinal endocrine cells and effects on intestinal blood flow and motility. Proc Natl Acad Sci U S A. 1982;79(14):4471–4475. doi: 10.1073/pnas.79.14.4471.
    1. Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, Nanni G, Pomp A, Castagneto M, Ghirlanda G, Rubino F. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366(17):1577–1585. doi: 10.1056/NEJMoa1200111.
    1. Milléo FQ, Malafaia O, Nassif PAN, Artoni RF, Santo MA. Comparative Study of the Effect of the Capella and Santoro Type II Surgical Techniques for Treatment of Obesity, regarding BMI and Peripheral Triglyceridemia. Rev Bras Videocir. 2006;4(4):151–161.
    1. Molin BD, Netto, Earthman CP, Cravo Bettini S, Grotti Clemente AP, Landi Masquio DC, Farias G, Boritza K, da Silva LG, von der Heyde ME, Dâmaso AR. Early effects of Roux-en-Y gastric bypass on peptides and hormones involved in the control of energy balance. Eur J Gastroenterol Hepatol. 2016;28(9):1050–1055. doi: 10.1097/MEG.0000000000000665.
    1. Motulsky HJ. Prism 5 Statistics Guide. 2007.
    1. Nauck MA, Meier JJ. The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions. Lancet Diabetes Endocrinol. 2016;4(6):525–536. doi: 10.1016/S2213-8587(15)00482-9.
    1. Santoro S, Milleo FQ, Malzoni CE, Klajner S, Borges PC, Santo MA, Campos FG, Artoni RF. Enterohormonal changes after digestive adaptation: five-year results of a surgical proposal to treat obesity and associated diseases. Obes Surg. 2008;18(1):17–26. doi: 10.1007/s11695-007-9371-0.
    1. Santoro S. Stomachs: does the size matter? Aspects of intestinal satiety, gastric satiety, hunger and gluttony. Clinics (Sao Paulo) 2012;67(4):301–303. doi: 10.6061/clinics/2012(04)01.
    1. Santoro S, Aquino CGG, Mota FC, Artoni RF. Does evolutionary biology help the understanding of metabolic surgery? A focused review. Arq Bras Cir Dig. 2020;33(1):e1503. doi: 10.1590/0102-672020190001e1503.
    1. Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, Thomas S, Abood B, Nissen SE, Bhatt DL. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366(17):1567–1576. doi: 10.1056/NEJMoa1200225.
    1. World Health Organization Fact Sheet . Obesity and overweight. 2017. [06 Oct 2020].

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