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

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Abstract:

Dahl K, Buschard K, Gram DX, d'Apice AJF, Hansen AK. Glucose intolerance in a xenotransplantation model: studies in alpha-gal knockout mice. APMIS 2006;114:805–11.

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 α-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 α-gal-bearing endothelia with natural α-gal antibodies in the human blood mediates hyperacute rejection of the xenograft. Alpha-galactosyl transferase knockout mice (α-GT KO) develop cataract, but no other lesions have been established in these mice. Here we report for the first time that α-GT KO mice have impaired glucose tolerance (p<0.001) and decreased insulin sensitivity (p<0.0001). Homeostasis model assessment shows impaired β-cell function (p<0.05). Similar physiological changes have not been examined in the α-galactosyl transferase pig. However, an association between α-galactosyl transferase knockout and impaired β-cell function could have critical importance for islet xenotransplantation.

Keywords: HOMA; Knockout; alpha-galactosyl transferase; glucose tolerance; mouse model; xenotransplantation

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0463.2006.apm_393.x

Affiliations: 1: Bartholin Institute, Rigshospitalet, 2: Novo Nordisk, Måløv, Denmark, and 3: St. Vincent's Hospital, Immunology Research Centre, Australia 4: The Royal Veterinary and Agricultural University, Department of Veterinary Pathobiology, Division of Laboratory Animal Science and Welfare, Frederiksberg,

Publication date: November 1, 2006

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