Reduction of Intestinal Electrogenic Glucose Absorption After Duodenojejunal Bypass in a Mouse Model
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
The role of intestinal glucose absorption in reducing glycemic levels after duodenojejunal bypass (DJB) is unclear. We hypothesized that DJB surgery decreases intestinal electrogenic glucose absorption by sodium glucose co-transporter 1 (SGLT1), leading to decreased glucose absorption and reduced blood glucose. Six groups of C57/BL6 mice were studied (n = 6 each) 2 weeks, 1 month, and 2 months after DJB or sham surgery.
Daily weight and food intake were measured for 1 month and an oral glucose tolerance test was performed 2 months after surgery. Electrogenic glucose absorption was quantified in an Ussing chamber according to the sodium-dependent increase of short-circuit current (Isc). Intestinal morphology was assessed by hematoxylin and eosin staining. Expression of SGLT1 was determined by quantitative PCR and Western blotting.
The DJB mice lost weight compared with the sham group and exhibited significant adaptive changes, with increased villus height, crypt depth, and villus surface area. Oral glucose absorption was significantly reduced in the DJB mice compared with the sham group. Glucose-induced Isc was significantly lower in the DJB mice than in the sham mice 1 and 2 months after surgery, indicating that SGLT1 activity was reduced after DJB. Transcript levels and protein abundance of SGLT1 after DJB were also decreased compared with the sham group.
DJB surgery reduced intestinal glucose absorption by reducing the activity and expression of the glucose transporter SGLT1, which represents a potential therapeutic target for patients with diabetes.
- Whiting DR, Guariguata L, Weil C, et al. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 2011;94(3):311–21. PMID: 22079683. CrossRef
- Danaei G, Finucane MM, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet. 2011;378(9785):31–40. PMID: 21705069. CrossRef
- Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366(17):1567–76. PMID: 22449319. CrossRef
- Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366(17):1577–85. PMID: 22449317. CrossRef
- Keating CL, Dixon JB, Moodie ML, et al. Cost-efficacy of surgically induced weight loss for the management of type 2 diabetes: a randomized controlled trial. Diabetes Care. 2009;32(4):580–4. PMID: 19171726. CrossRef
- Friedman MN, Sancetta AJ, Magovern GJ. The amelioration of diabetes mellitus following subtotal gastrectomy. Surg Gynecol Obstet. 1955;100(2):201–4. PMID: 13238177.
- Michalakis K, le Roux C. Gut hormones and leptin: impact on energy control and changes after bariatric surgery—what the future holds. Obes Surg. 2012;22(10):1648–57. PMID: 22692670. CrossRef
- Bosello O, Armellini F, Pelloso M, et al. Glucose tolerance in jejunoileal bypass for morbid obesity: a fifteen month follow-up. Diabete Metab. 1978;4(3):159–62. PMID: 710676.
- Ackerman NB. Observations on the improvements in carbohydrate metabolism in diabetic and other morbidly obese patients after jejunoileal bypass. Surg, Gynecol Obstet. 1981;152(5):581–6. PMID: 7013122.
- Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004;239(1):1–11. PMID: 14685093. CrossRef
- Isbell JM, Tamboli RA, Hansen EN, et al. The importance of caloric restriction in the early improvements in insulin sensitivity after Roux-en-Y gastric bypass surgery. Diabetes Care. 2010;33(7):1438–42. PMID: 20368410. CrossRef
- Stearns AT, Balakrishnan A, Tavakkolizadeh A. Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport. Am J Physiol Gastrointest Liver Physiol. 2009;297(5):G950–7. PMID: 20501442. CrossRef
- Gorboulev V, Schurmann A, Vallon V, et al. Na(+)-d-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes. 2012;61(1):187–96. PMID: 22124465. CrossRef
- Dyer J, Wood IS, Palejwala A, et al. Expression of monosaccharide transporters in intestine of diabetic humans. Am J Physiol Gastrointest Liver Physiol. 2002;282(2):G241–8. PMID: 11804845.
- Lan Z, Zassoko R, Liu W, et al. Development of techniques for gastrojejunal bypass surgery in obese mice. Microsurgery. 2010;30(4):289–95. PMID: 20049916.
- Liu W, Zassoko R, Mele T, et al. Establishment of duodenojejunal bypass surgery in mice: a model designed for diabetic research. Microsurgery. 2008;28(3):197–202. PMID: 18286660. CrossRef
- Woods M, Lan Z, Li J, et al. Antidiabetic effects of duodenojejunal bypass in an experimental model of diabetes induced by a high-fat diet. Br J Surg. 2011;98(5):686–96. PMID: 21381002. CrossRef
- Clarke LL. A guide to Ussing chamber studies of mouse intestine. Am J Physiol Gastrointest Liver Physiol. 2009;296(6):G1151–66. PMID: 19342508. CrossRef
- Artunc F, Rexhepaj R, Volkl H, et al. Impaired intestinal and renal glucose transport in PDK-1 hypomorphic mice. Am J Physiol Regul Integr Comp Physiol. 2006;291(5):R1533–8. PMID: 16741145. CrossRef
- Rexhepaj R, Rotte A, Gu S, et al. Tumor suppressor gene adenomatous polyposis coli downregulates intestinal transport. Pflugers Arch. 2011;461(5):527–36. PMID: 21476133. CrossRef
- Ray EC, Avissar NE, Sax HC. Methods used to study intestinal nutrient transport: past and present. J Surg Res. 2002;108(1):180–90. PMID: 12472108. CrossRef
- Whang EE, Dunn JC, Joffe H, et al. Enterocyte functional adaptation following intestinal resection. J Surg Res. 1996;60(2):370–4. PMID: 8598671. CrossRef
- Rexhepaj R, Alesutan I, Gu S, et al. SGK1-dependent stimulation of intestinal SGLT1 activity by vitamin D. Pflugers Arch. 2011;462(3):489–94. PMID: 21735060. CrossRef
- Nasir O, Artunc F, Wang K, et al. Downregulation of mouse intestinal Na(+)-coupled glucose transporter SGLT1 by gum arabic (Acacia senegal). Cell Physiol Biochem. 2010;25(2-3):203–10. PMID: 20110681. CrossRef
- Herrmann J, Schroder B, Klinger S, et al. Segmental diversity of electrogenic glucose transport characteristics in the small intestines of weaned pigs. Comp Biochem Physiol A Mol Integr Physiol. 2012;163(1):161–9. PMID: 22683689. CrossRef
- Stearns AT, Balakrishnan A, Radmanesh A, et al. Relative contributions of afferent vagal fibers to resistance to diet-induced obesity. Dig Dis Sci. 2012;57(5):1281–90. Epub 2011/12/06. PMID: 22138962. CrossRef
- Hyland NP, Rybicka JM, Ho W, et al. Adaptation of intestinal secretomotor function and nutrient absorption in response to diet-induced obesity. Neurogastroenterol Motil. 2010;22(6):e602–71. PMID: 20426798. CrossRef
- Balen D, Ljubojevic M, Breljak D, et al. Revised immunolocalization of the Na+- d-glucose cotransporter SGLT1 in rat organs with an improved antibody. Am J Physiol Cell Physiol. 2008;295(2):C475–89. PMID: 18524944. CrossRef
- Fatima J, Iqbal CW, Houghton SG, et al. Hexose transporter expression and function in mouse small intestine: role of diurnal rhythm. J Gastrointest Surg. 2009;13(4):634–41. PMID: 19082670. CrossRef
- Houghton SG, Iqbal CW, Duenes JA, et al. Coordinated, diurnal hexose transporter expression in rat small bowel: implications for small bowel resection. Surgery. 2008;143(1):79–93. PMID: 18154936. CrossRef
- Castaneda-Sceppa C, Castaneda F. Sodium-dependent glucose transporter protein as a potential therapeutic target for improving glycemic control in diabetes. Nutr Rev. 2011;69(12):720–9. PMID: 22133196. CrossRef
- Los EL, Wolters H, Stellaard F, et al. Intestinal capacity to digest and absorb carbohydrates is maintained in a rat model of cholestasis. Am J Physiol Gastrointest Liver Physiol. 2007;293(3):G615–22. PMID: 17627970. CrossRef
- Hirsh AJ, Cheeseman CI. Cholecystokinin decreases intestinal hexose absorption by a parallel reduction in SGLT1 abundance in the brush-border membrane. J Biol Chem. 1998;273(23):14545–9. PMID: 9603969. CrossRef
- Reduction of Intestinal Electrogenic Glucose Absorption After Duodenojejunal Bypass in a Mouse Model
Volume 23, Issue 9 , pp 1361-1369
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Duodenojejunal bypass
- Bariatric surgery
- Ussing chamber
- Glucose absorption
- Industry Sectors
- Author Affiliations
- 1. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery; First Affiliated Hospital, School of Medicine; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health; Key Laboratory of Organ Transplantation, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China