Insulin secretion and glucose metabolism in alpha 1,3-galactosyltransferase knock-out pigs compared to wild-type pigs

Anna Casu, Gabriel J. Echeverri, Rita Bottino, Dirk J. Van Der Windt, Jing He, Burcin Ekser, Suyapa Ball, David Ayares, David K C Cooper

Research output: Contribution to journalArticle

Abstract

Background: Xenotransplantation of porcine islets could be a valuable alternative to the shortage of human islets for transplantation. To overcome the immunological obstacle of antibody-mediated rejection, pigs homozygous for α1,3-galactosyltransferase gene knock-out (GT-KO) have been produced. The effect of this mutation on glucose metabolism is unknown. Methods: Glucose, insulin, C-peptide and glucagon levels were studied in eight adult pigs (four wild-type [WT] and four GT-KO) during intravenous glucose tolerance test (IVGTT), arginine stimulation test (AST), and insulin tolerance test (ITT). Morphological analysis of the pancreata was also performed. The in vitro insulin response to a high glucose concentration and theophylline were studied in a dynamic perfusion system with isolated islets. Results: Basal and stimulated blood glucose levels were similar in WT and GT-KO pigs. Basal insulin, C-peptide and glucagon were higher in GT-KO pigs. C-peptide and insulin responses to arginine and glucose were also higher in GT-KO animals. The reduction in blood glucose during ITT and IVGTT was similar in WT and GT-KO pigs. The extent of staining for insulin and glucagon in the pancreata were similar. The basal insulin secretion of isolated islets was higher in GT-KO pigs, while stimulation indexes for glucose and theophylline were similar to WT. Conclusions: GT-KO pigs demonstrated differences in glucose metabolism compared to WT pigs, the cause for which remains uncertain. It is unlikely that these differences would in any way affect the outcome of GT-KO porcine islet xenotransplantation.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalXenotransplantation
Volume17
Issue number2
DOIs
Publication statusPublished - Mar 2010

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Galactosyltransferases
Gene Knockout Techniques
Swine
Insulin
Glucose
C-Peptide
Glucagon
Heterologous Transplantation
Theophylline
Glucose Tolerance Test
Arginine
Blood Glucose
Pancreas
N-acetyllactosaminide alpha-1,3-galactosyltransferase
Islets of Langerhans Transplantation
Perfusion
Staining and Labeling
Mutation

Keywords

  • α1,3-galactosyltransferase gene-knockout
  • Arginine stimulation test
  • Glucose metabolism
  • Intravenous glucose tolerance test
  • Islets, porcine
  • Pig

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Casu, A., Echeverri, G. J., Bottino, R., Van Der Windt, D. J., He, J., Ekser, B., ... Cooper, D. K. C. (2010). Insulin secretion and glucose metabolism in alpha 1,3-galactosyltransferase knock-out pigs compared to wild-type pigs. Xenotransplantation, 17(2), 131-139. https://doi.org/10.1111/j.1399-3089.2010.00572.x

Insulin secretion and glucose metabolism in alpha 1,3-galactosyltransferase knock-out pigs compared to wild-type pigs. / Casu, Anna; Echeverri, Gabriel J.; Bottino, Rita; Van Der Windt, Dirk J.; He, Jing; Ekser, Burcin; Ball, Suyapa; Ayares, David; Cooper, David K C.

In: Xenotransplantation, Vol. 17, No. 2, 03.2010, p. 131-139.

Research output: Contribution to journalArticle

Casu, A, Echeverri, GJ, Bottino, R, Van Der Windt, DJ, He, J, Ekser, B, Ball, S, Ayares, D & Cooper, DKC 2010, 'Insulin secretion and glucose metabolism in alpha 1,3-galactosyltransferase knock-out pigs compared to wild-type pigs', Xenotransplantation, vol. 17, no. 2, pp. 131-139. https://doi.org/10.1111/j.1399-3089.2010.00572.x
Casu, Anna ; Echeverri, Gabriel J. ; Bottino, Rita ; Van Der Windt, Dirk J. ; He, Jing ; Ekser, Burcin ; Ball, Suyapa ; Ayares, David ; Cooper, David K C. / Insulin secretion and glucose metabolism in alpha 1,3-galactosyltransferase knock-out pigs compared to wild-type pigs. In: Xenotransplantation. 2010 ; Vol. 17, No. 2. pp. 131-139.
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