Recent insights in islet amyloid polypeptide-induced membrane disruption and its role in beta-cell death in type 2 diabetes mellitus.
The presence of fibrillar protein deposits (amyloid) of human islet amyloid polypeptide (hIAPP) in the pancreatic islets of Langerhans is thought to be related to death of the insulin-producing islet beta-cells in type 2 diabetes mellitus (DM2). The mechanism of hIAPP-induced beta-cell death is not understood. However, there is growing evidence that hIAPP-induced disruption of beta-cell membranes is the cause of hIAPP cytotoxicity. Amyloid cytotoxicity by membrane damage has not only been suggested for hIAPP, but also for peptides and proteins related to other misfolding diseases, like Alzheimer's disease, Parkinson's disease, and prion diseases. Here we review the interaction of hIAPP with membranes, and discuss recent progress in the field, with a focus on hIAPP structure and on the proposed mechanisms of hIAPP-induced membrane damage in relation to beta-cell death in DM2.
Khemtémourian
Lucie
L
Department of Metabolic and Endocrine Diseases, Division of Biomedical Genetics, University Medical Center Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands.
Killian
J Antoinette
JA
Höppener
Jo W M
JW
Engel
Maarten F M
MF
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D016923:Cell Death; D002462:Cell Membrane / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D011487:Protein Conformation; D015398:Signal Transduction
D000682:Amyloid; D058228:Islet Amyloid Polypeptide