eprintid: 10148592 rev_number: 8 eprint_status: archive userid: 699 dir: disk0/10/14/85/92 datestamp: 2022-05-17 14:10:44 lastmod: 2022-05-17 14:10:44 status_changed: 2022-05-17 14:10:44 type: article metadata_visibility: show sword_depositor: 699 creators_name: Sevcuka, Adriana creators_name: White, Kenneth creators_name: Terry, Cassandra title: Factors That Contribute to hIAPP Amyloidosis in Type 2 Diabetes Mellitus ispublished: pub divisions: C07 divisions: DF9 divisions: B02 divisions: UCL keywords: Science & Technology, Life Sciences & Biomedicine, Biology, Microbiology, Life Sciences & Biomedicine - Other Topics, human islet amyloid polypeptide, amyloidosis, type 2 diabetes mellitus, aggregation, INSULIN-DEGRADING ENZYME, ENDOPLASMIC-RETICULUM STRESS, OXIDATIVE STRESS, THERAPEUTIC TARGET, POLYPEPTIDE IAPP, BETA, AMYLIN, MEMBRANE, MECHANISM, DEGRADATION note: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. abstract: Cases of Type 2 Diabetes Mellitus (T2DM) are increasing at an alarming rate due to the rise in obesity, sedentary lifestyles, glucose-rich diets and other factors. Numerous studies have increasingly illustrated the pivotal role that human islet amyloid polypeptide (hIAPP) plays in the pathology of T2DM through damage and subsequent loss of pancreatic β-cell mass. HIAPP can misfold and form amyloid fibrils which are preceded by pre-fibrillar oligomers and monomers, all of which have been linked, to a certain extent, to β-cell cytotoxicity through a range of proposed mechanisms. This review provides an up-to-date summary of recent progress in the field, highlighting factors that contribute to hIAPP misfolding and aggregation such as hIAPP protein concentration, cell stress, molecular chaperones, the immune system response and cross-seeding with other amyloidogenic proteins. Understanding the structure of hIAPP and how these factors affect amyloid formation will help us better understand how hIAPP misfolds and aggregates and, importantly, help identify potential therapeutic targets for inhibiting amyloidosis so alternate and more effective treatments for T2DM can be developed. date: 2022-04-01 date_type: published publisher: MDPI official_url: https://doi.org/10.3390/life12040583 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1950433 doi: 10.3390/life12040583 medium: Electronic pii: life12040583 lyricists_name: Terry, Cassandra lyricists_id: CTERR78 actors_name: Terry, Cassandra actors_id: CTERR78 actors_role: owner full_text_status: public publication: Life volume: 12 number: 4 article_number: 583 pages: 19 event_location: Switzerland citation: Sevcuka, Adriana; White, Kenneth; Terry, Cassandra; (2022) Factors That Contribute to hIAPP Amyloidosis in Type 2 Diabetes Mellitus. Life , 12 (4) , Article 583. 10.3390/life12040583 <https://doi.org/10.3390/life12040583>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10148592/1/life-12-00583.pdf