title: Death and dysfunction of transplanted β-cells: lessons learned from type 2 diabetes?
abstract: β-Cell replacement by islet transplantation is a potential curative therapy for type 1 diabetes. Despite advancements in islet procurement and immune suppression that have increased islet transplant survival, graft function progressively declines, and many recipients return to insulin dependence within a few years posttransplant. The progressive loss of β-cell function in islet transplants seems unlikely to be explained by allo- and autoimmune-mediated mechanisms alone and in a number of ways resembles β-cell failure in type 2 diabetes. That is, both following transplantation and in type 2 diabetes, islets exhibit decreased first-phase glucose-stimulated insulin secretion, impaired proinsulin processing, inflammation, formation of islet amyloid, signs of oxidative and endoplasmic reticulum stress, and β-cell death. These similarities suggest common mechanisms may underlie loss of insulin production in both type 2 diabetes and islet transplantation and point to the potential for therapeutic approaches used in type 2 diabetes that target the β-cell, such as incretin-based therapies, as adjuncts for immunosuppression in islet transplantation.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Potter
authors.forename: Clara Y
authors.initials: CY
authors.lastname: Westwell-Roper
authors.forename: Agnieszka M
authors.initials: AM
authors.lastname: Klimek-Abercrombie
authors.forename: Garth L
authors.initials: GL
authors.lastname: Warnock
authors.forename: C Bruce
authors.initials: CB
authors.lastname: Verchere
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000473:pathology / Q000502:physiology* / Q000637:transplantation; D016381:Islets of Langerhans Transplantation
chemical_list: D007328:Insulin