Glucose intolerance in a xenotransplantation model: studies in alpha-gal knockout mice

Kirsten Dahl, Karsten Buschard, Dorte X. Gram, Anthony J.F. d'Apice, Axel Kornerup Hansen

    9 Citations (Scopus)

    Abstract

    Xenotransplantation holds the promise of replacing failing human organs with organs of animal origin. Transplantation of pancreatic islets from pigs to humans might restore glucose homeostasis and offer diabetic patients considerable improvement in their quality of life. The alpha-gal epitope, present in all mammals except humans, apes and Old World monkeys, is a decisive obstruction to successful xenotransplantation of vascularized organs as the reaction of alpha-gal-bearing endothelia with natural alpha-gal antibodies in the human blood mediates hyperacute rejection of the xenograft. Alpha-galactosyl transferase knockout mice (alpha-GT KO) develop cataract, but no other lesions have been established in these mice. Here we report for the first time that alpha-GT KO mice have impaired glucose tolerance (p < 0.001) and decreased insulin sensitivity (p < 0.0001). Homeostasis model assessment shows impaired beta-cell function (p < 0.05). Similar physiological changes have not been examined in the alpha-galactosyl transferase pig. However, an association between alpha-galactosyl transferase knockout and impaired beta-cell function could have critical importance for islet xenotransplantation.
    Original languageEnglish
    JournalActa Pathologica Microbiologica et Immunologica Scandinavica
    Volume114
    Issue number11
    Pages (from-to)805-811
    Number of pages7
    ISSN0903-4641
    Publication statusPublished - 2006

    Keywords

    • Former LIFE faculty
    • glucose
    • alpha-gal epitope
    • Xenotransplantation
    • Glucose intolerance

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