Biological hypoxia in pre-transplant human pancreatic islets induces transplant failure in diabetic mice

Evaluating the quality of isolated human islets before transplantation is crucial for predicting the success in treating Type 1 diabetes. The current gold standard involves time-intensive in vivo transplantation into diabetic immunodeficient mice. Given the susceptibility of isolated islets to hypox...

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Bibliographic Details
Published in:Scientific reports 2024-05, Vol.14 (1), p.12402-11, Article 12402
Main Authors: Kato, Hiroyuki, Salgado, Mayra, Mendez, Daniel, Gonzalez, Nelson, Rawson, Jeffrey, Ligot, Doreen, Balandran, Bennie, Orr, Chris, Quijano, Janine C., Omori, Keiko, Qi, Meirigeng, Al-Abdullah, Ismail H., Mullen, Yoko, Ku, Hsun Teresa, Kandeel, Fouad, Komatsu, Hirotake
Format: Article
Language:English
Subjects:
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Animals
Blood Glucose - metabolism
Cell Hypoxia
Diabetes
Diabetes mellitus (insulin dependent)
Diabetes Mellitus, Experimental - therapy
Diabetes Mellitus, Type 1 - metabolism
Female
Gene expression
Humanities and Social Sciences
Humans
Hypoxia
Hypoxia - metabolism
Immunodeficiency
Islet cells
Islets of Langerhans - metabolism
Islets of Langerhans Transplantation - methods
Male
Mice
Middle Aged
multidisciplinary
Pancreatic islet transplantation
Regression analysis
Science
Science (multidisciplinary)
Transplantation
Transplants & implants
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Summary:Evaluating the quality of isolated human islets before transplantation is crucial for predicting the success in treating Type 1 diabetes. The current gold standard involves time-intensive in vivo transplantation into diabetic immunodeficient mice. Given the susceptibility of isolated islets to hypoxia, we hypothesized that hypoxia present in islets before transplantation could indicate compromised islet quality, potentially leading to unfavorable outcomes. To test this hypothesis, we analyzed expression of 39 hypoxia-related genes in human islets from 85 deceased donors. We correlated gene expression profiles with transplantation outcomes in 327 diabetic mice, each receiving 1200 islet equivalents grafted into the kidney capsule. Transplantation outcome was post-transplant glycemic control based on area under the curve of blood glucose over 4 weeks. In linear regression analysis, DDIT4 (R = 0.4971, P  
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-61604-3