REVIEW ARTICLE
Metabolic stress, IAPP and islet amyloid
J. Montane,
A. Klimek-Abercrombie,
K. J. Potter,
C. Westwell-Roper,
C. Bruce Verchere,
J. Montane
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
Search for more papers by this authorA. Klimek-Abercrombie
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
Search for more papers by this authorK. J. Potter
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
Search for more papers by this authorC. Westwell-Roper
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
Search for more papers by this authorCorresponding Author
C. Bruce Verchere
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
Department of Surgery, Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada
Correspondence to: Bruce Verchere, PhD, Child & Family Research Institute, 950 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4.
E-mail: bverchere@cfri.ca
Search for more papers by this author
J. Montane,
A. Klimek-Abercrombie,
K. J. Potter,
C. Westwell-Roper,
C. Bruce Verchere,
J. Montane
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
Search for more papers by this authorA. Klimek-Abercrombie
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
Search for more papers by this authorK. J. Potter
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
Search for more papers by this authorC. Westwell-Roper
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
Search for more papers by this authorCorresponding Author
C. Bruce Verchere
Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
Department of Surgery, Child & Family Research Institute, University of British Columbia, Vancouver, BC, Canada
Correspondence to: Bruce Verchere, PhD, Child & Family Research Institute, 950 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4.
E-mail: bverchere@cfri.ca
Search for more papers by this authorAbstract
Amyloid forms within pancreatic islets in type 2 diabetes from aggregates of the β-cell peptide islet amyloid polypeptide (IAPP). These aggregates are toxic to β-cells, inducing β-cell death and dysfunction, as well as inciting islet inflammation. The β-cell is subject to a number of other stressors, including insulin resistance and hyperglycaemia, that may contribute to amyloid formation by increasing IAPP production by the β-cell. β-Cell dysfunction, evident as impaired glucose-stimulated insulin secretion and defective prohormone processing and exacerbated by metabolic stress, is also a likely prerequisite for islet amyloid formation to occur in type 2 diabetes. Islet transplants in patients with type 1 diabetes face similar stressors, and are subject to rapid amyloid formation and impaired proinsulin processing associated with progressive loss of β-cell function and mass. Declining β-cell mass is predicted to increase metabolic demand on remaining β-cells, promoting a feed-forward cycle of β-cell decline.
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