Antidiabetic effects of duodenojejunal bypass in an experimental model of diabetes induced by a high-fat diet

Authors

  • M. Woods,

    1. Children's Health Research Institute, University of Western Ontario, London
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  • Z. Lan,

    1. Department of Surgery, University of Western Ontario, London
    2. Department of Multi-Organ Transplant Program, London Health Sciences Center, London
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  • J. Li,

    1. Children's Health Research Institute, University of Western Ontario, London
    2. Department of Physiology and Pharmacology, University of Western Ontario, London
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  • M. B. Wheeler,

    1. Department of Physiology, University of Toronto, Toronto, Ontario, Canada
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  • H. Wang,

    1. Department of Surgery, University of Western Ontario, London
    2. Department of Multi-Organ Transplant Program, London Health Sciences Center, London
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  • R. Wang

    Corresponding author
    1. Children's Health Research Institute, University of Western Ontario, London
    2. Department of Physiology and Pharmacology, University of Western Ontario, London
    3. Department of Medicine, University of Western Ontario, London
    • Victoria Research Laboratories, Room A5-140, 800 Commissioners Road East, London, Ontario, N6C 2V5, Canada
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  • Presented in part to the Annual Meeting of the American Association of Anatomists, New Orleans, Louisiana, USA, April 2009, and published in abstract form as FASEB J 2009; 23(Meeting Abstract Suppl): 825.8

Abstract

Background:

Obese patients with type II diabetes who undergo bariatric surgery revert to normal blood glucose and insulin levels, and develop a dramatic increase in insulin sensitivity. However, the mechanisms involved are unknown. This study characterized pancreatic islet and duodenojejunal enteroendocrine cells in normal mice and those with diabetes induced by a high-fat diet (HFD) following duodenojejunal bypass (DJB).

Methods:

C57BL/6J mice, fed for 8 weeks either a normal diet (n = 10) or a HFD (n = 10) resulting in a hyperglycaemic state, underwent DJB (connection of the distal end of the jejunum to the distal stomach and direction of biliopancreatic secretions to the distal jejunum). Metabolic and immunohistological analyses were carried out on the pancreas and gastrointestinal tract.

Results:

A significant decrease in fasting blood glucose was observed in normal-DJB and HFD-DJB mice 1 week after the operation, with improved glucose tolerance at 4 weeks. There were no changes in pancreatic β-cell mass, but an increase in the ratio of α-cell to β-cell mass was observed in the DJB groups. Furthermore, the number of cells expressing Pdx-1, glucagon-like peptide 1, pancreatic polypeptide and synaptophysin was increased in the bypassed duodenum and/or gastrojejunum of the DJB groups.

Conclusion:

Both normal and obese diabetic mice that underwent DJB displayed improved glucose tolerance and a reduction in fasting blood glucose, which mimicked findings in obese diabetic patients following bariatric surgery. The present data suggest that an increase in specific enteroendocrine cell populations may play a critical role in normalizing glucose homeostasis. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

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