Skip to main content
Top
Published in: Surgical Endoscopy 4/2018

01-04-2018

Understanding intestinal glucose transporter expression in obese compared to non-obese subjects

Authors: Rebecca A. Deal, Yueming Tang, Reid Fletcher, Alfonso Torquati, Philip Omotosho

Published in: Surgical Endoscopy | Issue 4/2018

Login to get access

Abstract

Introduction

The impact of Roux-en-Y gastric bypass (RYGB) on weight loss and co-morbid disease resolution is well established. However, the mechanisms underlying the procedure remain incompletely understood. Intestinal remodeling involving glucose transporters (GLUTs) may play a crucial role. Rat studies have demonstrated morphological adaptation of GLUTs within adipose and intestinal cells in association with the reprogramming of glucose metabolism. There is a limited understanding of the variations in expression amongst GLUT family receptors in the human intestine. The aim of this study was to evaluate and describe jejunal GLUT expression patterns in the obese versus non-obese.

Methods

Tissue samples were collected from 19 adults (age ≥18) patients with morbid obesity undergoing elective RYGB. Specimens were obtained from excess jejunum removed during the stapled jejuno-jejunal anastomosis. All subjects met National Institutes of Health criteria for bariatric surgery (body mass index or BMI ≥40 or ≥35 with obesity-related comorbidities). Exclusion criteria included age less than 18, age greater than 65, patients undergoing a revision procedure, and the presence of a seizure disorder (possible association with GLUT-1 deficiency syndrome). Five samples were obtained from non-obese subjects (average BMI 26.7) without diabetes who were consenting organ donors after brain death. Samples of jejunum from non-obese individuals were obtained at the time of organ procurement. Institutional Review Board and Gift of Hope approval was obtained. Specimens underwent quantitative real-time PCR and Western blotting. Western blot densitometry was performed using Image J software. Student T test was performed using SPSS statistics software.

Results

GLUT-1 and GLUT-7 expression were not detected in the jejunum of either group. No difference in expression pattern was observed for GLUT-2, GLUT-4, and GLUT-9 between the groups. Western blot band density of GLUT-5 to loading control (GADPH) mean ratio was 0.21 (SD = 0.20) in obese specimens compared to 0.56 (SD = 0.17) in non-obese. Densitometry revealed GLUT-5 levels in the jejunum of the obese were significantly lower than non-obese specimens (P < 0.05).

Conclusion

The absence of GLUT-1 expression in both the obese and non-obese groups is consistent with the established view of GLUT-1 being abundantly present in fetal intestine but diminished to negligible levels by adulthood. Decreased GLUT-5 expression in samples from subjects with obesity compared to non-obese samples may represent a down-regulation of gene expression amongst the obese. The differential expression of GLUT-5 suggests a possible role in obesity. Studies of GLUT family expression will aid in understanding the impact of intestinal remodeling on obesity.
Literature
2.
go back to reference Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, Thomas S, Abood B, Nissen SE, Bhatt DL (2012) Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 366:1567–1576CrossRefPubMedPubMedCentral Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, Thomas S, Abood B, Nissen SE, Bhatt DL (2012) Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 366:1567–1576CrossRefPubMedPubMedCentral
3.
go back to reference Sjöström L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, Dahlgren S, Larsson B, Narbro K, Sjöström CD, Sullivan M, Wedel H, Swedish Obese Subjects Study Scientific Group (2004) Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 351:2683–2693CrossRefPubMed Sjöström L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, Dahlgren S, Larsson B, Narbro K, Sjöström CD, Sullivan M, Wedel H, Swedish Obese Subjects Study Scientific Group (2004) Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 351:2683–2693CrossRefPubMed
4.
go back to reference Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, Barakat HA, deRamon RA, Israel G, Dolezal JM (1995) Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 222:339–350 (discussion 350–2) CrossRefPubMedPubMedCentral Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, Barakat HA, deRamon RA, Israel G, Dolezal JM (1995) Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 222:339–350 (discussion 350–2) CrossRefPubMedPubMedCentral
5.
go back to reference Schauer PR, Burguera B, Ikramuddin S, Cottam D, Gourash W, Hamad G, Eid GM, Mattar S, Ramanathan K, Barinas-Mitchell E, Rao RH, Kuller L, Kelley D (2003) Effect of laparoscopic Roux-en-Y gastric bypass on type-2 diabetes mellitus. Ann Surg 238:467–484 (discussion 84–5) PubMedPubMedCentral Schauer PR, Burguera B, Ikramuddin S, Cottam D, Gourash W, Hamad G, Eid GM, Mattar S, Ramanathan K, Barinas-Mitchell E, Rao RH, Kuller L, Kelley D (2003) Effect of laparoscopic Roux-en-Y gastric bypass on type-2 diabetes mellitus. Ann Surg 238:467–484 (discussion 84–5) PubMedPubMedCentral
6.
go back to reference Saeidi N, Meoli L, Nestoridi E, Gupta NK, Kvas S, Kucharczyk J, Bonab AA, Fischman AJ, Yarmush ML, Stylopoulos N (2013) Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Science 341:406–410CrossRefPubMedPubMedCentral Saeidi N, Meoli L, Nestoridi E, Gupta NK, Kvas S, Kucharczyk J, Bonab AA, Fischman AJ, Yarmush ML, Stylopoulos N (2013) Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Science 341:406–410CrossRefPubMedPubMedCentral
7.
go back to reference Thorens B (1996) Glucose transporters in the regulation of intestinal, renal, and liver glucose fluxes. Am J Physiol 270:G541–G553PubMed Thorens B (1996) Glucose transporters in the regulation of intestinal, renal, and liver glucose fluxes. Am J Physiol 270:G541–G553PubMed
8.
go back to reference Mueckler M, Thorens B (2013) The SLC2 (GLUT) family of membrane transporters. Mol Asp Med 34:121–138CrossRef Mueckler M, Thorens B (2013) The SLC2 (GLUT) family of membrane transporters. Mol Asp Med 34:121–138CrossRef
9.
go back to reference Pascual JM, Ronen GM (2015) Glucose transporter type 1 deficiency (G1D) at 25 (1990–2015): presumptions, facts, and the lives of persons with this rare disease. Pediatr Neurol 53:379–393CrossRefPubMedPubMedCentral Pascual JM, Ronen GM (2015) Glucose transporter type 1 deficiency (G1D) at 25 (1990–2015): presumptions, facts, and the lives of persons with this rare disease. Pediatr Neurol 53:379–393CrossRefPubMedPubMedCentral
10.
go back to reference Tang Y, Zhang L, Forsyth CB, Shaikh M, Song S, Keshavarzian A (2015) The role of miR-212 and iNOS in alcohol-induced intestinal barrier dysfunction and steatohepatitis. Alcohol Clin Exp Res 39:1632–1641CrossRefPubMedPubMedCentral Tang Y, Zhang L, Forsyth CB, Shaikh M, Song S, Keshavarzian A (2015) The role of miR-212 and iNOS in alcohol-induced intestinal barrier dysfunction and steatohepatitis. Alcohol Clin Exp Res 39:1632–1641CrossRefPubMedPubMedCentral
11.
go back to reference Tang Y, Banan A, Forsyth CB, Fields JZ, Lau CK, Zhang LJ, Keshavarzian A (2008) Effect of alcohol on miR-212 expression in intestinal epithelial cells and its potential role in alcoholic liver disease. Alcohol Clin Exp Res 32:355–364CrossRefPubMed Tang Y, Banan A, Forsyth CB, Fields JZ, Lau CK, Zhang LJ, Keshavarzian A (2008) Effect of alcohol on miR-212 expression in intestinal epithelial cells and its potential role in alcoholic liver disease. Alcohol Clin Exp Res 32:355–364CrossRefPubMed
12.
go back to reference Thomas S, Schauer P (2010) Bariatric surgery and the gut hormone response. Nutr Clin Pract 25:175–182CrossRefPubMed Thomas S, Schauer P (2010) Bariatric surgery and the gut hormone response. Nutr Clin Pract 25:175–182CrossRefPubMed
14.
go back to reference Abdeen G, le Roux CW (2016) Mechanisms underlying weight loss and complications of Roux-en-Y gastric bypass. A review. Obes Surg 26:410–421CrossRefPubMed Abdeen G, le Roux CW (2016) Mechanisms underlying weight loss and complications of Roux-en-Y gastric bypass. A review. Obes Surg 26:410–421CrossRefPubMed
15.
go back to reference van Dijk SJ, Molloy PL, Varinli H, Morrison JL, Muhlhauser BS, Members of EpiSCOPE (2015) Epigenetics and human obesity. Int J Obes (Lond) 39:85–97CrossRef van Dijk SJ, Molloy PL, Varinli H, Morrison JL, Muhlhauser BS, Members of EpiSCOPE (2015) Epigenetics and human obesity. Int J Obes (Lond) 39:85–97CrossRef
16.
go back to reference Heymsfield SB, Wadden TA (2017) Mechanisms, pathophysiology, and management of obesity. N Engl J Med 376:254–266CrossRefPubMed Heymsfield SB, Wadden TA (2017) Mechanisms, pathophysiology, and management of obesity. N Engl J Med 376:254–266CrossRefPubMed
17.
go back to reference Muekler M, Thorens B (2013) The SLC2 (GLUT) family of membrane transporters. Mol Asp Med 34(2–3):121–138CrossRef Muekler M, Thorens B (2013) The SLC2 (GLUT) family of membrane transporters. Mol Asp Med 34(2–3):121–138CrossRef
18.
go back to reference Stumpel F, Burcelin R, Jungermann K, Thorens B (2001) Normal kinetics of intestinal glucose absorption in the absence of GLUT2: evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum. Proc Natl Acad Sci USA 98(20):11330–11335CrossRefPubMedPubMedCentral Stumpel F, Burcelin R, Jungermann K, Thorens B (2001) Normal kinetics of intestinal glucose absorption in the absence of GLUT2: evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum. Proc Natl Acad Sci USA 98(20):11330–11335CrossRefPubMedPubMedCentral
19.
go back to reference Hevener AL, Reichart D, Olefsky J (2000) Exercise and thiazolidinedione therapy normalize insulin action in the obese Zucker fatty rat. Diabetes 49(12):2154–2159CrossRefPubMed Hevener AL, Reichart D, Olefsky J (2000) Exercise and thiazolidinedione therapy normalize insulin action in the obese Zucker fatty rat. Diabetes 49(12):2154–2159CrossRefPubMed
20.
go back to reference Kim JC (2016) The effect of exercise training combined with PPARγ agonist on skeletal muscle glucose uptake and insulin sensitivity in induced diabetic obese Zucker rats. J Exerc Nutr Biochem 20(2):42–50CrossRef Kim JC (2016) The effect of exercise training combined with PPARγ agonist on skeletal muscle glucose uptake and insulin sensitivity in induced diabetic obese Zucker rats. J Exerc Nutr Biochem 20(2):42–50CrossRef
22.
go back to reference Garcia-Herrera J, Abad B, Rodriguez-Yoldi MJ (2003) Effect of lipopolysaccharide on d-fructose transport across rabbit jejunum. Inflamm Res 52:177–184CrossRefPubMed Garcia-Herrera J, Abad B, Rodriguez-Yoldi MJ (2003) Effect of lipopolysaccharide on d-fructose transport across rabbit jejunum. Inflamm Res 52:177–184CrossRefPubMed
23.
go back to reference Garcia-Herrera J, Navarro MA, Marca MC, de la Osada J, Rodriguez-Yoldi MJ (2004) The effect of tumor necrosis factor-alpha on d-fructose intestinal transport in rabbits. Cytokine 25:21–30CrossRefPubMed Garcia-Herrera J, Navarro MA, Marca MC, de la Osada J, Rodriguez-Yoldi MJ (2004) The effect of tumor necrosis factor-alpha on d-fructose intestinal transport in rabbits. Cytokine 25:21–30CrossRefPubMed
24.
go back to reference Jurjus A, Barada K, Khoury N, Assef MD, Foltzer CJ, Reimund JM, Kedinger M (2006) Morphological and biochemical alterations in the jejunum following iodoacetamide-induced colitis in rats. Can J Physiol Pharmacol 84:1191–1203CrossRefPubMed Jurjus A, Barada K, Khoury N, Assef MD, Foltzer CJ, Reimund JM, Kedinger M (2006) Morphological and biochemical alterations in the jejunum following iodoacetamide-induced colitis in rats. Can J Physiol Pharmacol 84:1191–1203CrossRefPubMed
25.
go back to reference Lertanekawattana S, Wichatrong T, Chaisiri K, Uchikawa R, Arizono N (2005) Expression of cytokines and monosaccharide transporters in the duodenal mucosa of patients with gastrointestinal symptoms in rural Thailand. Southeast Asian J Trop Med Public Health 36:923–930PubMed Lertanekawattana S, Wichatrong T, Chaisiri K, Uchikawa R, Arizono N (2005) Expression of cytokines and monosaccharide transporters in the duodenal mucosa of patients with gastrointestinal symptoms in rural Thailand. Southeast Asian J Trop Med Public Health 36:923–930PubMed
26.
go back to reference Gregor MF, Hotamisligil GS (2011) Inflammation mechanisms in obesity. Annu Rev Immunol 29:4115–4145CrossRef Gregor MF, Hotamisligil GS (2011) Inflammation mechanisms in obesity. Annu Rev Immunol 29:4115–4145CrossRef
27.
go back to reference Chessman C (2008) GLUT7: a new intestinal facilitated hexose transporter. Am J Physiol Endocrinol Metab 295(2):E238–E241CrossRef Chessman C (2008) GLUT7: a new intestinal facilitated hexose transporter. Am J Physiol Endocrinol Metab 295(2):E238–E241CrossRef
28.
go back to reference Li Q, Manolescu A, Ritzel M, Yao S, Slugoski M, Young JD, Chen X-Z, Cheeseman CI (2004) Cloning and functional characterization of the human GLUT7 isoform SLC2A7 from the small intestine. Am J Physiol Gastrointest Liver Physiol 287(1):G236–G242CrossRefPubMed Li Q, Manolescu A, Ritzel M, Yao S, Slugoski M, Young JD, Chen X-Z, Cheeseman CI (2004) Cloning and functional characterization of the human GLUT7 isoform SLC2A7 from the small intestine. Am J Physiol Gastrointest Liver Physiol 287(1):G236–G242CrossRefPubMed
29.
go back to reference Doblado M, Mobley KH (2009) Facilitative glucose transporter 9, a unique hexose and urate transporter. Am J Physiol Endocrinol Metab 297(4):E831–E835CrossRefPubMedPubMedCentral Doblado M, Mobley KH (2009) Facilitative glucose transporter 9, a unique hexose and urate transporter. Am J Physiol Endocrinol Metab 297(4):E831–E835CrossRefPubMedPubMedCentral
30.
go back to reference Bueter M, Löwenstein C, Olbers T, Wang M, Cluny NL, Bloom SR, Sharkey KA, Lutz TA, le Roux CW (2010) Gastric bypass increases energy expenditure in rats. Gastroenterology 138:1845–1853CrossRefPubMed Bueter M, Löwenstein C, Olbers T, Wang M, Cluny NL, Bloom SR, Sharkey KA, Lutz TA, le Roux CW (2010) Gastric bypass increases energy expenditure in rats. Gastroenterology 138:1845–1853CrossRefPubMed
31.
go back to reference Mumphrey MB, Patterson LM, Zheng H, Berthoud HR (2013) Roux-en-Y gastric bypass surgery increases number but not density of CCK-, GLP-1, 5-HT-, and neurotensin-expressing enteroendocrine cells in rats. Neurogastroenterol Motil 25:e70–e79. doi:10.1111/nmp.12034 CrossRefPubMed Mumphrey MB, Patterson LM, Zheng H, Berthoud HR (2013) Roux-en-Y gastric bypass surgery increases number but not density of CCK-, GLP-1, 5-HT-, and neurotensin-expressing enteroendocrine cells in rats. Neurogastroenterol Motil 25:e70–e79. doi:10.​1111/​nmp.​12034 CrossRefPubMed
32.
go back to reference Stearns AT, Balakrishnan A, Tavakkolizadeh A (2009) Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport. Am J Physiol Gastrointest Liver Physiol 297:G950–G957CrossRefPubMedPubMedCentral Stearns AT, Balakrishnan A, Tavakkolizadeh A (2009) Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport. Am J Physiol Gastrointest Liver Physiol 297:G950–G957CrossRefPubMedPubMedCentral
33.
go back to reference le Roux CW, Borg C, Wallis K, Vincent RP, Bueter M, Goodlad R, Ghatei MA, Patel A, Bloom SR, Aylwin SJ (2010) Gut hypertrophy after gastric bypass is associated with increased glucagon-like peptide 2 and intestinal crypt cell proliferation. Ann Surg 252:50–56CrossRefPubMed le Roux CW, Borg C, Wallis K, Vincent RP, Bueter M, Goodlad R, Ghatei MA, Patel A, Bloom SR, Aylwin SJ (2010) Gut hypertrophy after gastric bypass is associated with increased glucagon-like peptide 2 and intestinal crypt cell proliferation. Ann Surg 252:50–56CrossRefPubMed
34.
go back to reference Cavin JB, Couvelard A, Lebtahi R, Ducroc R, Arapis K, Voitellier E, Cluzeaud F, Gillard L, Hourseau M, Mikail N, Ribeiro-Parenti L, Kapel N, Marmuse JP, Bado A, Gall ML (2016) Differences in alimentary glucose absorption and intestinal disposal of blood glucose after Roux-en-Y gastric bypass vs sleeve gastrectomy. Gastroenterology 150:454–464CrossRefPubMed Cavin JB, Couvelard A, Lebtahi R, Ducroc R, Arapis K, Voitellier E, Cluzeaud F, Gillard L, Hourseau M, Mikail N, Ribeiro-Parenti L, Kapel N, Marmuse JP, Bado A, Gall ML (2016) Differences in alimentary glucose absorption and intestinal disposal of blood glucose after Roux-en-Y gastric bypass vs sleeve gastrectomy. Gastroenterology 150:454–464CrossRefPubMed
Metadata
Title
Understanding intestinal glucose transporter expression in obese compared to non-obese subjects
Authors
Rebecca A. Deal
Yueming Tang
Reid Fletcher
Alfonso Torquati
Philip Omotosho
Publication date
01-04-2018
Publisher
Springer US
Published in
Surgical Endoscopy / Issue 4/2018
Print ISSN: 0930-2794
Electronic ISSN: 1432-2218
DOI
https://doi.org/10.1007/s00464-017-5858-5

Other articles of this Issue 4/2018

Surgical Endoscopy 4/2018 Go to the issue