{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:28:08Z","timestamp":1791203288235,"version":"4.2.0"},"reference-count":358,"publisher":"Walter de Gruyter GmbH","issue":"2","funder":[{"name":"Department of Biotechnology, Ministry of Science and Technology","award":["BT\/RLF\/Re-entry\/11\/2012"],"award-info":[{"award-number":["BT\/RLF\/Re-entry\/11\/2012"]}]},{"DOI":"10.13039\/501100010892","name":"Department of Science and Technology","doi-asserted-by":"crossref","award":["EMR\/2016\/002798"],"award-info":[{"award-number":["EMR\/2016\/002798"]}],"id":[{"id":"10.13039\/501100010892","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"crossref","award":["(09\/137\/06.2) 2019 EMR-I"],"award-info":[{"award-number":["(09\/137\/06.2) 2019 EMR-I"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University Grants Commission","award":["F.4-5(18-FRP)(IV-Cycle)\/2017(BSR)"],"award-info":[{"award-number":["F.4-5(18-FRP)(IV-Cycle)\/2017(BSR)"]}]},{"name":"Wadhwani Research center for Bioengineering","award":["RD\/0118-DONWR04-001"],"award-info":[{"award-number":["RD\/0118-DONWR04-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The human islet amyloid polypeptide (hIAPP) or amylin, a neuroendocrine peptide hormone, is known to misfold and form amyloidogenic aggregates that have been observed in the pancreas of 90% subjects with Type 2 Diabetes Mellitus (T2DM). Under normal physiological conditions, hIAPP is co-stored and co-secreted with insulin; however, under chronic hyperglycemic conditions associated with T2DM, the overexpression of hIAPP occurs that has been associated with the formation of amyloid deposits; as well as the death and dysfunction of pancreatic \u03b2-islets in T2DM. Hitherto, various biophysical and structural studies have shown that during this process of aggregation, the peptide conformation changes from random structure to helix, then to \u03b2-sheet, subsequently to cross \u03b2-sheets, which finally form left-handed helical aggregates. The intermediates, formed during this process, have been shown to induce higher cytotoxicity in the \u03b2-cells by inducing cell membrane disruption, endoplasmic reticulum stress, mitochondrial dysfunction, oxidative stress, islet inflammation, and DNA damage. As a result, several research groups have attempted to target both hIAPP aggregation phenomenon and the destabilization of preformed fibrils as a therapeutic intervention for T2DM management. In this review, we have summarized structural aspects of various forms of hIAPP viz. monomer, oligomers, proto-filaments, and fibrils of hIAPP. Subsequently, cellular toxicity caused by toxic conformations of hIAPP has been elaborated upon. Finally, the need for performing structural and toxicity studies\n                    <jats:italic>in vivo<\/jats:italic>\n                    to fill in the gap between the structural and cellular aspects has been discussed.\n                  <\/jats:p>","DOI":"10.1515\/hsz-2020-0174","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T10:47:46Z","timestamp":1598611666000},"page":"133-153","source":"Crossref","is-referenced-by-count":58,"title":["Human islet amyloid polypeptide (hIAPP) - a curse in type II diabetes mellitus: insights from structure and toxicity studies"],"prefix":"10.1515","volume":"402","author":[{"given":"Ajit Kumar","family":"Bishoyi","sequence":"first","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratiksha H.","family":"Roham","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune, 411007, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavitha","family":"Rachineni","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreyada","family":"Save","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Asrafuddoza","family":"Hazari","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpy","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune, 411007, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","reference":[{"key":"ref341","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.2337\/db08-0926","article-title":"Degradation of cAMP-responsive element\u2013binding protein by the ubiquitin-proteasome pathway contributes to glucotoxicity in \u03b2-cells and human pancreatic islets","volume":"58","year":"2009","journal-title":"Diabetes"},{"key":"ref2011","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.sbi.2012.11.003","article-title":"Aggregation of islet amyloid polypeptide: from physical chemistry to cell biology","volume":"23","year":"2013a","journal-title":"Curr. 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