1. Biological hypoxia in pre-transplant human pancreatic islets induces transplant failure in diabetic mice.
- Author
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Kato, Hiroyuki, Salgado, Mayra, Mendez, Daniel, Gonzalez, Nelson, Rawson, Jeffrey, Ligot, Doreen, Balandran, Bennie, Orr, Chris, Quijano, Janine, Omori, Keiko, Qi, Meirigeng, Al-Abdullah, Ismail, Mullen, Yoko, Ku, Hsun, Kandeel, Fouad, and Komatsu, Hirotake
- Subjects
Humans ,Animals ,Islets of Langerhans Transplantation ,Mice ,Islets of Langerhans ,Diabetes Mellitus ,Experimental ,Male ,Diabetes Mellitus ,Type 1 ,Hypoxia ,Female ,Cell Hypoxia ,Middle Aged ,Blood Glucose - Abstract
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
- Published
- 2024