TY - JOUR
T1 - Metabolic stress, IAPP and islet amyloid
AU - Montané Mogas, Joel
AU - Klimek-Abercrombie, A.
AU - Potter, K. J.
AU - Westwell-Roper, C.
AU - Verchere, C. Bruce
N1 - The authors wish to acknowledge funding support from the Canadian Institutes of Health Research (CIHR; MOP-14862) and the Canadian Diabetes Association (CDA; OG-3-11-3413-CV) for the studies described in this manuscript. C. Bruce Verchere is an investigator of the Child & Family Research Institute and the Irving K Barber Chair in Diabetes Research at the University of British Columbia. J. Montane is supported by a post-doctoral fellowship from the Juvenile Diabetes Research Foundation, A. Klimek-Abercrombie by the CIHR Transplant Training Program, C. Westwell-Roper by a Vanier Canada Graduate Scholarship, and K. J. Potter by a Rx&D/CIHR MD PhD Studentship and CDA.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Amylin
KW - Diabetes
KW - Insulin
KW - β-cell
UR - http://www.scopus.com/inward/record.url?scp=84865578671&partnerID=8YFLogxK
UR - https://www.webofscience.com/wos/woscc/full-record/WOS:000308038300009
U2 - 10.1111/j.1463-1326.2012.01657.x
DO - 10.1111/j.1463-1326.2012.01657.x
M3 - Article
C2 - 22928566
AN - SCOPUS:84865578671
SN - 1462-8902
VL - 14
SP - 68
EP - 77
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - Suppl. 3
ER -