title: Isolated human islets require hyperoxia to maintain islet mass, metabolism, and function.
abstract: Pancreatic islet transplantation has been recognized as an effective treatment for Type 1 diabetes; however, there is still plenty of room to improve transplantation efficiency. Because islets are metabolically active they require high oxygen to survive; thus hypoxia after transplant is one of the major causes of graft failure. Knowing the optimal oxygen tension for isolated islets would allow a transplant team to provide the best oxygen environment during pre- and post-transplant periods. To address this issue and begin to establish empirically determined guidelines for islet maintenance, we exposed in vitro cultured islets to different partial oxygen pressures (pO2) and assessed changes in islet volume, viability, metabolism, and function. Human islets were cultured for 7 days in different pO2 media corresponding to hypoxia (90 mmHg), normoxia (160 mmHg), and hyerpoxia (270 or 350 mmHg). Compared to normoxia and hypoxia, hyperoxia alleviated the loss of islet volume, maintaining higher islet viability and metabolism as measured by oxygen consumption and glucose-stimulated insulin secretion responses. We predict that maintaining pre- and post-transplanted islets in a hyperoxic environment will alleviate islet volume loss and maintain islet quality thereby improving transplant outcomes.
authors.affiliation: Division of Developmental and Translational Diabetes and Endocrinology Research, Department of Diabetes and Metabolic Researches, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA. Electronic address: hkomatsu@coh.org.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Komatsu
authors.affiliation: Department of Electrical Engineering, California Institute of Technology, 1200 E California Blvd. MC 136-93, Pasadena, CA 91125, USA.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Kang
authors.affiliation: Division of Developmental and Translational Diabetes and Endocrinology Research, Department of Diabetes and Metabolic Researches, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Leonard
authors.initials: L
authors.lastname: Medrano
authors.affiliation: Division of Developmental and Translational Diabetes and Endocrinology Research, Department of Diabetes and Metabolic Researches, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Barriga
authors.affiliation: Division of Developmental and Translational Diabetes and Endocrinology Research, Department of Diabetes and Metabolic Researches, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mendez
authors.affiliation: Division of Developmental and Translational Diabetes and Endocrinology Research, Department of Diabetes and Metabolic Researches, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rawson
authors.affiliation: Division of Developmental and Translational Diabetes and Endocrinology Research, Department of Diabetes and Metabolic Researches, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Omori
authors.affiliation: Division of Developmental and Translational Diabetes and Endocrinology Research, Department of Diabetes and Metabolic Researches, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ferreri
authors.affiliation: Department of Electrical Engineering, California Institute of Technology, 1200 E California Blvd. MC 136-93, Pasadena, CA 91125, USA.
authors.forename: Yu-Chong
authors.initials: YC
authors.lastname: Tai
authors.affiliation: Division of Developmental and Translational Diabetes and Endocrinology Research, Department of Diabetes and Metabolic Researches, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Fouad
authors.initials: F
authors.lastname: Kandeel
authors.affiliation: Division of Developmental and Translational Diabetes and Endocrinology Research, Department of Diabetes and Metabolic Researches, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mullen
mesh_terms: D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000502:physiology*; D009924:Organ Culture Techniques / Q000379:methods*; D010100:Oxygen / Q000378:metabolism*
chemical_list: D007328:Insulin; D010100:Oxygen
keywords: Hyperoxia; Hypoxia; Insulin secretion; Islet viability; Islet volume; Oxygen consumption rate