Glucose intolerance in a xenotransplantation model: studies in alpha-gal knockout mice
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Glucose intolerance in a xenotransplantation model : studies in alpha-gal knockout mice. / Dahl, Kirsten; Buschard, Karsten; Gram, Dorte X.; d'Apice, Anthony J.F.; Hansen, Axel Kornerup.
I: Acta Pathologica Microbiologica et Immunologica Scandinavica, Bind 114, Nr. 11, 2006, s. 805-811.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Glucose intolerance in a xenotransplantation model
T2 - studies in alpha-gal knockout mice
AU - Dahl, Kirsten
AU - Buschard, Karsten
AU - Gram, Dorte X.
AU - d'Apice, Anthony J.F.
AU - Hansen, Axel Kornerup
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - Former LIFE faculty
KW - glukose
KW - glucose
KW - alpha-gal epitope
KW - Xenotransplantation
KW - Glucose intolerance
M3 - Journal article
VL - 114
SP - 805
EP - 811
JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
SN - 0903-4641
IS - 11
ER -
ID: 8041827