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 language | English |
|---|---|
| Pages (from-to) | 131-139 |
| Number of pages | 9 |
| Journal | Xenotransplantation |
| Volume | 17 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Mar 2010 |
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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
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 journal › Article
}
TY - JOUR
T1 - Insulin secretion and glucose metabolism in alpha 1,3-galactosyltransferase knock-out pigs compared to wild-type pigs
AU - Casu, Anna
AU - Echeverri, Gabriel J.
AU - Bottino, Rita
AU - Van Der Windt, Dirk J.
AU - He, Jing
AU - Ekser, Burcin
AU - Ball, Suyapa
AU - Ayares, David
AU - Cooper, David K C
PY - 2010/3
Y1 - 2010/3
N2 - 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.
AB - 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.
KW - α1,3-galactosyltransferase gene-knockout
KW - Arginine stimulation test
KW - Glucose metabolism
KW - Intravenous glucose tolerance test
KW - Islets, porcine
KW - Pig
UR - http://www.scopus.com/inward/record.url?scp=77951056004&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951056004&partnerID=8YFLogxK
U2 - 10.1111/j.1399-3089.2010.00572.x
DO - 10.1111/j.1399-3089.2010.00572.x
M3 - Article
C2 - 20522245
AN - SCOPUS:77951056004
VL - 17
SP - 131
EP - 139
JO - Xenotransplantation
JF - Xenotransplantation
SN - 0908-665X
IS - 2
ER -