{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T11:00:24Z","timestamp":1761562824324,"version":"build-2065373602"},"reference-count":59,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This research was supported by the Basic Science Research Program through the National Re-search Foundation of Korea (NRF) funded by the Ministry of Education","award":["2020R1I1A1A01060627"],"award-info":[{"award-number":["2020R1I1A1A01060627"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human amylin or islet amyloid polypeptide (hIAPP) is synthesized in the pancreatic \u03b2-cells and has been shown to contribute to the pathogenesis of type 2 diabetes (T2D) in vitro and in vivo. This study compared amylin oligomerization\/expression and signal transduction under endoplasmic reticulum (ER) stress and oxidative stress. pCMV-hIAPP-overexpressing INS-1E cells presented different patterns of amylin oligomerization\/expression under ER stress and oxidative stress. Amylin oligomerization\/expression under ER stress showed three amylin oligomers of less than 15 kDa size in pCMV-hIAPP-overexpressing cells, while one band was detected under oxidative stress. Under ER stress conditions, HIF1\u03b1, p-ERK, CHOP, Cu\/Zn-SOD, and Bax were significantly increased in pCMV-hIAPP-overexpressing cells compared to the pCMV-Entry-expressing cells (control), whereas p-Akt, p-mTOR, Mn-SOD, catalase, and Bcl-2 were significantly decreased. Under oxidative stress conditions, HIF1\u03b1, p-ERK, CHOP, Mn-SOD, catalase, and Bcl-2 were significantly reduced in pCMV-hIAPP-overexpressing cells compared to the control, whereas p-mTOR, Cu\/Zn-SOD, and Bax were significantly increased. In mitochondrial oxidative phosphorylation (OXPHOS), the mitochondrial complex I and complex IV were significantly decreased under ER stress conditions and significantly increased under oxidative stress conditions in pCMV-hIAPP-overexpressing cells compared to the control. The present study results demonstrate that amylin undergoes oligomerization under ER stress in pCMV-hIAPP-overexpressing cells. In addition, human amylin overexpression under ER stress in the pancreatic \u03b2 cells may enhance amylin protein aggregation, resulting in \u03b2-cell dysfunction.<\/jats:p>","DOI":"10.3390\/ijms222111341","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T21:29:46Z","timestamp":1634765386000},"page":"11341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Human Islet Amyloid Polypeptide Overexpression in INS-1E Cells Influences Amylin Oligomerization under ER Stress and Oxidative Stress"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1732-8494","authenticated-orcid":false,"given":"Yeong-Min","family":"Yoo","sequence":"first","affiliation":[{"name":"East Coast Life Sciences Institute, College of Life Science, Gangneung-Wonju National University, Gangneung 25457, Gangwon-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Soo","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Marine Life Sciences, College of Life Science, Gangneung-Wonju National University, Gangneung 25457, Gangwon-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1021\/acschembio.8b00690","article-title":"Amyloidogenicity, Cytotoxicity, and Receptor Activity of Bovine Amylin: Implications for Xenobiotic Transplantation and the Design of Nontoxic Amylin Variants","volume":"13","author":"Akter","year":"2018","journal-title":"ACS Chem. 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