Linking hIAPP misfolding and aggregation with type 2 diabetes mellitus: a structural perspective

Hassan, Shahab, White, Kenneth and Terry, Cassandra (2022) Linking hIAPP misfolding and aggregation with type 2 diabetes mellitus: a structural perspective. Bioscience reports, 42 (5). pp. 1-24. ISSN 1573-4935

Abstract

There are over 40 identified human disorders that involve certain proteins folding incorrectly, accumulating in the body causing damage to cells and organs and causing disease. Type 2 Diabetes Mellitus is one of these protein misfolding disorders and involves human islet amyloid polypeptide misfolding and accumulating in parts of the body, primarily in the pancreas causing damage to islet cells and affecting glucose regulation. In this review, we have summarised our current understanding of what causes hIAPP to misfold, what conformations are found in different parts of the body with a particular focus on what is known about the structure of hIAPP and how this links to Type 2 Diabetes Mellitus. Understanding the molecular basis behind these misfolding events is essential for understanding the role of hIAPP to develop better therapeutics since type 2 diabetes currently affects over 4.9 million people in the UK alone and is predicted to increase as our population ages.

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