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Duodenal–Jejunal Bypass Surgery Does Not Increase Skeletal Muscle Insulin Signal Transduction or Glucose Disposal in Goto–Kakizaki Type 2 Diabetic Rats

  • Physiology Research
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Abstract

Background

Duodenal–jejunal bypass (DJB) has been shown to reverse type 2 diabetes (T2DM) in Goto–Kakizaki (GK) rats, a rodent model of non-obese T2DM. Skeletal muscle insulin resistance is a hallmark decrement in T2DM. The aim of the current work was to investigate the effects of DJB on skeletal muscle insulin signal transduction and glucose disposal. It was hypothesized that DJB would increase skeletal muscle insulin signal transduction and glucose disposal in GK rats.

Methods

DJB was performed in GK rats. Sham operations were performed in GK and nondiabetic Wistar–Kyoto (WKY) rats. At 2 weeks post-DJB, oral glucose tolerance (OGTT) was measured. At 3 weeks post-DJB, insulin-induced signal transduction and glucose disposal were measured in skeletal muscle.

Results

In GK rats and compared to sham operation, DJB did not (1) improve fasting glucose or insulin, (2) improve OGTT, or (3) increase skeletal muscle insulin signal transduction or glucose disposal. Interestingly, skeletal muscle glucose disposal was similar between WKY-Sham, GK-Sham, and GK-DJB.

Conclusions

Bypassing of the proximal small intestine does not increase skeletal muscle glucose disposal. The lack of skeletal muscle insulin resistance in GK rats questions whether this animal model is adequate to investigate the etiology and treatments for T2DM. Additionally, bypassing of the foregut may lead to different findings in other animal models of T2DM as well as in T2DM patients.

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References

  1. American Diabetes Association. Economic costs of diabetes in the U.S. in 2002. Diabetes Care. 2003;26:917–32.

    Google Scholar 

  2. Brozinick Jr JT, Roberts BR, Dohm GL. Defective signaling through Akt-2 and -3 but not Akt-1 in insulin-resistant human skeletal muscle: potential role in insulin resistance. Diabetes. 2003;52:935–41.

    Article  CAS  PubMed  Google Scholar 

  3. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292:1724–37.

    Article  CAS  PubMed  Google Scholar 

  4. Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122:248–56. e245.

    Article  PubMed  Google Scholar 

  5. Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470–81.

    Article  CAS  PubMed  Google Scholar 

  6. Chou CJ, Membrez M, Blancher F. Gut decontamination with norfloxacin and ampicillin enhances insulin sensitivity in mice. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:127–37. discussion 137–140.

    Article  CAS  PubMed  Google Scholar 

  7. Cohen RV, Schiavon CA, Pinheiro JS, et al. Duodenal–jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22–34 kg/m(2): a report of 2 cases. Surg Obes Relat Dis. 2007;3:195–7.

    Article  PubMed  Google Scholar 

  8. Corcoran MP, Lamon-Fava S, Fielding RA. Skeletal muscle lipid deposition and insulin resistance: effect of dietary fatty acids and exercise. Am J Clin Nutr. 2007;85:662–77.

    CAS  PubMed  Google Scholar 

  9. Dadke S, Kusari J, Chernoff J. Down-regulation of insulin signaling by protein-tyrosine phosphatase 1B is mediated by an N-terminal binding region. J Biol Chem. 2000;275:23642–7.

    Article  CAS  PubMed  Google Scholar 

  10. DeFronzo RA, Ferrannini E, Simonson DC. Fasting hyperglycemia in non-insulin-dependent diabetes mellitus: contributions of excessive hepatic glucose production and impaired tissue glucose uptake. Metabolism. 1989;38:387–95.

    Article  CAS  PubMed  Google Scholar 

  11. DeFronzo RA, Jacot E, Jequier E, et al. The effect of insulin on the disposal of glucose: results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes. 1981;30:1000–7.

    CAS  PubMed  Google Scholar 

  12. Dohm GL, Kasperek GJ, Tapscott EB, et al. Effect of exercise on synthesis and degradation of muscle protein. Biochem J. 1980;188:255–62.

    CAS  PubMed  Google Scholar 

  13. Dolan PL, Tapscott EB, Dorton PJ, et al. Contractile activity restores insulin responsiveness in skeletal muscle of obese Zucker rats. Biochem J. 1993;289(Pt 2):423–6.

    CAS  PubMed  Google Scholar 

  14. Ferzli GS, Dominique E, Ciaglia M, et al. Clinical improvement after duodenojejunal bypass for nonobese type 2 diabetes despite minimal improvement in glycemic homeostasis. World J Surg. 2009;33:972–9.

    Article  CAS  PubMed  Google Scholar 

  15. Friedman JE, Dohm GL, Leggett-Frazier N, et al. Restoration of insulin responsiveness in skeletal muscle of morbidly obese patients after weight loss. Effect on muscle glucose transport and glucose transporter GLUT4. J Clin Invest. 1992;89:701–5.

    Article  CAS  PubMed  Google Scholar 

  16. Geloneze B, Geloneze SR, Fiori C, et al. Surgery for nonobese type 2 diabetic patients: an interventional study with duodenal–jejunal exclusion. Obes Surg. 2009;19:1077–83.

    Article  PubMed  Google Scholar 

  17. Krein SL, Funnell MM, Piette JD. Economics of diabetes mellitus. Nurs Clin North Am. 2006;41:499–511. v–vi.

    Article  PubMed  Google Scholar 

  18. Krook A, Kawano Y, Song XM, et al. Improved glucose tolerance restores insulin-stimulated Akt kinase activity and glucose transport in skeletal muscle from diabetic Goto–Kakizaki rats. Diabetes. 1997;46:2110–4.

    Article  CAS  PubMed  Google Scholar 

  19. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  CAS  PubMed  Google Scholar 

  20. Membrez M, Blancher F, Jaquet M, et al. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB J. 2008;22:2416–26.

    Article  CAS  PubMed  Google Scholar 

  21. Movassat J, Bailbe D, Lubrano-Berthelier C, et al. Follow-up of GK rats during prediabetes highlights increased insulin action and fat deposition despite low insulin secretion. Am J Physiol Endocrinol Metab. 2008;294:E168–75.

    Article  CAS  PubMed  Google Scholar 

  22. Petersen KF, Shulman GI. Etiology of insulin resistance. Am J Med. 2006;119:S10–6.

    Article  PubMed  Google Scholar 

  23. Pories WJ, Caro JF, Flickinger EG, et al. The control of diabetes mellitus (NIDDM) in the morbidly obese with the Greenville gastric bypass. Ann Surg. 1987;206:316–23.

    Article  CAS  PubMed  Google Scholar 

  24. Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222:339–50. discussion 350–332.

    Article  CAS  PubMed  Google Scholar 

  25. Portha B, Serradas P, Bailbe D, et al. Beta-cell insensitivity to glucose in the GK rat, a spontaneous nonobese model for type II diabetes. Diabetes. 1991;40:486–91.

    Article  CAS  PubMed  Google Scholar 

  26. Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006;244:741–9.

    Article  PubMed  Google Scholar 

  27. 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;239:1–11.

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by an East Carolina University Research Development grant (TP Gavin) and a National Institute on Health grant-R01 DK046121 (GL Dohm).

Conflicts of Interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Human Performance Laboratory, East Carolina University, 363 Ward Sports Medicine Bldg., Greenville, NC, 27858, USA

    Timothy P. Gavin, Ruben C. Sloan III, Eric Z. Lukosius, Melissa A. Reed, Robert D. McKernie & Kushal Parikh

  2. Department of Exercise and Sport Science, East Carolina University, Greenville, NC, 27858, USA

    Timothy P. Gavin, Ruben C. Sloan III, Eric Z. Lukosius, Melissa A. Reed, Robert D. McKernie & Kushal Parikh

  3. Department of Physiology, East Carolina University, Greenville, NC, 27858, USA

    Timothy P. Gavin, Robert D. McKernie, Kushal Parikh, J. William Price, Edward B. Tapscott & G. Lynis Dohm

  4. Department of Surgery, East Carolina University, Greenville, NC, 27858, USA

    John R. Pender, Van Boghossian, Jacqueline J. Carter & Walter J. Pories

  5. East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, 27858, USA

    Timothy P. Gavin

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  1. Timothy P. Gavin
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Correspondence to Timothy P. Gavin.

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Gavin, T.P., Sloan, R.C., Lukosius, E.Z. et al. Duodenal–Jejunal Bypass Surgery Does Not Increase Skeletal Muscle Insulin Signal Transduction or Glucose Disposal in Goto–Kakizaki Type 2 Diabetic Rats. OBES SURG 21, 231–237 (2011). https://doi.org/10.1007/s11695-010-0304-y

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