Recent Insights in Islet Amyloid Polypeptide-Induced Membrane Disruption and Its Role in<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>β</mml:mi></mml:math>-Cell Death in Type 2 Diabetes Mellitus

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  • Lucie Khemtémourian
    Department of Metabolic and Endocrine Diseases, Division of Biomedical Genetics, University Medical Center Utrecht, P.O. Box 85090, 3508 AB Utrecht, The Netherlands
  • J. Antoinette Killian
    Department of Metabolic and Endocrine Diseases, Division of Biomedical Genetics, University Medical Center Utrecht, P.O. Box 85090, 3508 AB Utrecht, The Netherlands
  • Jo W. M. Höppener
    Research group Chemical Biology and Organic Chemistry, Bijvoet Institute and Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
  • Maarten F. M. Engel
    Department of Metabolic and Endocrine Diseases, Division of Biomedical Genetics, University Medical Center Utrecht, P.O. Box 85090, 3508 AB Utrecht, The Netherlands

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<jats:p>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<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>β</mml:mi></mml:math>-cells in type 2 diabetes mellitus (DM2). The mechanism of hIAPP-induced<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>β</mml:mi></mml:math>-cell death is not understood. However, there is growing evidence that hIAPP-induced disruption of<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>β</mml:mi></mml:math>-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<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>β</mml:mi></mml:math>-cell death in DM2.</jats:p>

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