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

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

SN - 0903-465X

VL - 114

SP - 805

EP - 811

JO - APMIS. Supplementum

JF - APMIS. Supplementum

IS - 11

ER -