Death and Dysfunction of Transplanted β-Cells: Lessons Learned From Type 2 Diabetes?

  1. C. Bruce Verchere1,2,3
  1. 1Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
  2. 2Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada
  3. 3Department of Surgery, University of British Columbia, Vancouver, BC, Canada
  1. Corresponding author: C. Bruce Verchere, bverchere{at}cfri.ca.

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.

  • Received April 20, 2012.
  • Accepted October 1, 2013.

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