title: Intraportal islet oxygenation.
abstract: Islet transplantation (IT) is a promising therapy for the treatment of diabetes. The large number of islets required to achieve insulin independence limit its cost-effectiveness and the number of patients who can be treated. It is believed that >50% of islets are lost in the immediate post-IT period. Poor oxygenation in the early post-IT period is recognized as a possible reason for islet loss and dysfunction but has not been extensively studied. Several key variables affect oxygenation in this setting, including (1) local oxygen partial pressure (pO(2)), (2) islet oxygen consumption, (3) islet size (diameter, D), and (4) presence or absence of thrombosis on the islet surface. We discuss implications of oxygen-limiting conditions on intraportal islet viability and function. Of the 4 key variables, the islet size appears to be the most important determinant of the anoxic and nonfunctional islet volume fractions. Similarly, the effect of thrombus formation on the islet surface may be substantial. At the University of Minnesota, average size distribution data from clinical alloislet preparations (n = 10) indicate that >150-µm D islets account for only ~30% of the total islet number, but >85% of the total islet volume. This suggests that improved oxygen supply to the islets may have a profound impact on islet survivability and function since most of the β-cell volume is within large islets which are most susceptible to oxygen-limiting conditions. The assumption that the liver is a suitable islet transplant site from the standpoint of oxygenation should be reconsidered.
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Suszynski
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Efstathios S
authors.initials: ES
authors.lastname: Avgoustiniatos
authors.affiliation: Department of Surgery, University of Arizona, Tucson, AZ, USA kkpapas@surgery.arizona.edu.
authors.forename: Klearchos K
authors.initials: KK
authors.lastname: Papas
mesh_terms: D000818:Animals; D016923:Cell Death; D015687:Cell Hypoxia; D048429:Cell Size; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000601:surgery*; D006085:Graft Survival; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D016896:Treatment Outcome
chemical_list: D010100:Oxygen
keywords: anoxia; hypoxia; intraportal transplant; islet transplant; oxygenation