Metabolic stress, IAPP and islet amyloid.

J Montane, A Klimek-Abercrombie, K J Potter, C Westwell-Roper, C Bruce Verchere

Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.

Diabetes, obesity & metabolism 2012 Oct

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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. © 2012 Blackwell Publishing Ltd.

Citation

J Montane, A Klimek-Abercrombie, K J Potter, C Westwell-Roper, C Bruce Verchere. Metabolic stress, IAPP and islet amyloid. Diabetes, obesity & metabolism. 2012 Oct;14 Suppl 3:68-77