{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:31:16Z","timestamp":1773307876848,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31602021"],"award-info":[{"award-number":["31602021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["qnyncw-kqlhtxm"],"award-info":[{"award-number":["qnyncw-kqlhtxm"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Collection, Utilization and Innovation of Animal Resources by Research Institutes and Enterprises of Chongqing","award":["31602021"],"award-info":[{"award-number":["31602021"]}]},{"name":"Collection, Utilization and Innovation of Animal Resources by Research Institutes and Enterprises of Chongqing","award":["qnyncw-kqlhtxm"],"award-info":[{"award-number":["qnyncw-kqlhtxm"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epinephrine influences the function of pancreatic \u03b2-cells, primarily through the \u03b12A-adrenergic receptor (\u03b12A-AR) on their plasma membrane. Previous studies indicate that epinephrine transiently suppresses insulin secretion, whereas prolonged exposure induces its compensatory secretion. Nonetheless, the impact of epinephrine-induced \u03b12A-AR signaling on the survival and function of pancreatic \u03b2-cells, particularly the impact of reprogramming after their removal from sustained epinephrine stimulation, remains elusive. In the present study, we applied MIN6, a murine insulinoma cell line, with 3 days of high concentration epinephrine incubation and 2 days of standard incubation, explored cell function and activity, and analyzed relevant regulatory pathways. The results showed that chronic epinephrine incubation led to the desensitization of \u03b12A-AR and enhanced insulin secretion. An increased number of docked insulin granules and impaired Syntaxin-2 was found after chronic epinephrine exposure. Growth curve and cell cycle analyses showed the inhibition of cell proliferation. Transcriptome analysis showed the occurrence of endoplasmic reticulum stress (ER stress) and oxidative stress, such as the presence of BiP, CHOP, IRE1, ATF4, and XBP, affecting cellular endoplasmic reticulum function and survival, along with UCP2, OPA1, PINK, and PRKN, associated with mitochondrial dysfunction. Consequently, we conclude that chronic exposure to epinephrine induces \u03b12A-AR desensitization and leads to ER and oxidative stress, impairing protein processing and mitochondrial function, leading to modified pancreatic \u03b2-cell secretory function and cell fate.<\/jats:p>","DOI":"10.3390\/ijms25137029","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T05:11:39Z","timestamp":1719465099000},"page":"7029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Chronic Epinephrine-Induced Endoplasmic Reticulum and Oxidative Stress Impairs Pancreatic \u03b2-Cells Function and Fate"],"prefix":"10.3390","volume":"25","author":[{"given":"Ran","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingpeng","family":"Yao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6490-5923","authenticated-orcid":false,"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5851-0439","authenticated-orcid":false,"given":"Sean W.","family":"Limesand","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9256-8856","authenticated-orcid":false,"given":"Yongju","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7960-7352","authenticated-orcid":false,"given":"Xiaochuan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"166","DOI":"10.2337\/diabetes.54.1.166","article-title":"Predictors of and Longitudinal Changes in Insulin Sensitivity and Secretion Preceding Onset of Type 2 Diabetes","volume":"54","author":"Lyssenko","year":"2005","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41574-020-0325-0","article-title":"Insights into pancreatic islet cell dysfunction from type 2 diabetes mellitus genetics","volume":"16","author":"Krentz","year":"2020","journal-title":"Nat. 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