Evidence map›Paper›PMID 25382150›Full record

ArticleXenotransplantation

Glucose metabolism in pigs expressing human genes under an insulin promoter.

Martin Wijkstrom, Rita Bottino, Hayoto Iwase, Hidetaka Hara, Burcin Ekser, Dirk van der Windt, Cassandra Long, Frederico G S Toledo, Carol J Phelps, Massimo Trucco and 2 more

Open access · greenAbstract read
In one paragraph

Article in Xenotransplantation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
5.9field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 39 citations in OpenAlex.

  1. Contributions of Europeans to Xenotransplantation Research: 2. Pig Islet and Cell Xenotransplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Review
  2. Double transgenic neonatal porcine islets as an alternative source for beta cell replacement therapy.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  3. Pig Xenotransplantation in Beta Cell Replacement: Addressing Challenges and Harnessing Potential for Type 1 Diabetes Therapy.Transplant international : official journal of the European Society for Organ Transplantation · 2024
    Review
  4. Review
  5. Review
  6. Article
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  10. [Research progress on the donor cell sources of pancreatic islet transplantation for treatment of diabetes mellitus].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2018
    Review
  11. The Future of Islet Transplantation Is Now.Frontiers in medicine · 2018
    Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Re-engineering islet cell transplantation.Pharmacological research · 2015
    Review
  18. Article
  19. Article
  20. Pig-to-monkey islet xenotransplantation using multi-transgenic pigs.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2014
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Martin WijkstromThomas E. Starzl Transplantation Institute, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Rita Bottino
Hayoto Iwase
Hidetaka Hara
Burcin Ekser
Dirk van der Windt
Cassandra Long
Frederico G S Toledo
Carol J Phelps
Massimo Trucco
David K C Cooper
David Ayares
University of Pittsburgh · US

Funding

University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8M
Prolonging life-supported pig kidney and heart graft survival in baboons by suppressing inflammationU19AI090959 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COOPER, DAVID KC · 2010 to 2024
$26.3M
Interdisciplinary Training in Transplantation BiologyT32AI074490 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Angus W Thomson · 2007 to 2026
$4.2M
Thromboregulation to Prevent Thrombotic MicroangiopathyU01AI068642 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COOPER, DAVID KC · 2005 to 2008
$2.7M
NCATS NIH HHS UL1 TR000005NIAID NIH HHS T32 AI 074490NIAID NIH HHS T32 AI074490NIAID NIH HHS U01 AI068642NIAID NIH HHS U19 AI090959NIAID NIH HHS U19 AI090959-01PHS HHS R21 A1074844
6 · The paper itself

Abstract

backgroundXenotransplantation of porcine islets can reverse diabetes in non-human primates. The remaining hurdles for clinical application include safe and effective T-cell-directed immunosuppression, but protection against the innate immune system and coagulation dysfunction may be more difficult to achieve. Islet-targeted genetic manipulation of islet-source pigs represents a powerful tool to protect against graft loss. However, whether these genetic alterations would impair islet function is unknown.

methodsOn a background of α1,3-galactosyltransferase gene-knockout (GTKO)/human (h)CD46, additional genes (hCD39, human tissue factor pathway inhibitor, porcine CTLA4-Ig) were inserted in different combinations under an insulin promoter to promote expression in islets (confirmed by immunofluorescence). Seven pigs were tested for baseline and glucose/arginine-challenged levels of glucose, insulin, C-peptide, and glucagon.

resultsThis preliminary study did not show definite evidence of β-cell deficiencies, even when three transgenes were expressed under the insulin promoter. Of seven animals, all were normoglycemic at fasting, and five of seven had normal glucose disposal rates after challenge. All animals exhibited insulin, C-peptide, and glucagon responses to both glucose and arginine challenge; however, significant interindividual variation was observed.

conclusionsMultiple islet-targeted transgenic expression was not associated with an overtly detrimental effect on islet function, suggesting that complex genetic constructs designed for islet protection warrants further testing in islet xenotransplantation models.

Indexed as

Promoter Regions, GeneticAbataceptAnimalsAnimals, Genetically ModifiedAntigens, CDApyraseArginineBlood GlucoseCell LineC-PeptideFastingFibroblastsGalactosyltransferasesGene Expression RegulationGene Knockout TechniquesGenes, SyntheticAbataceptalpha-1,3-galactosyltransferase 1, porcineAntigens, CDApyraseArginineBlood GlucoseCD39 antigenCD46 protein, humanC-PeptideGalactosyltransferasesGlucagonGlucoseInsulinlipoprotein-associated coagulation inhibitorLipoproteinsMembrane Cofactor ProteinRecombinant Fusion Proteinsarginine stimulation testC-peptidegenetic engineeringglucagoninsulinIVGTTpigxenotransplantation

Identifiers

PMID25382150
PMCPMC4329053
OpenAlexW1995107329

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.