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Emerging evidence highlights \u03b2-arrestin2 as a key mediator of apoptosis and fibrosis beyond classical G protein signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Insulin resistance was induced in rats by subcutaneous dexamethasone (10 mg\/kg\/day) for 7 days. The therapeutic effects of carvedilol, phenylephrine, phenylephrine + carvedilol, propranolol, doxazosin, and doxazosin + propranolol were evaluated in relation to glucose homeostasis and pancreatic apoptotic\/fibrotic signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Conclusion:<\/jats:title>\n                    <jats:p>Dexamethasone impaired glucose homeostasis, expanded islet mass, and triggered pancreatic cell apoptosis and fibrosis via upregulated BAX\/Bcl-2 expression ratio, downregulated cAMP, upregulated PKA, ERK1\/2, and CREB expression with elevated PKB activity and reduced FOXO1 expression. % Level of \u03b2-arrestin2 was reduced in pancreatic islets and elevated in exocrine pancreas in relation to the aforementioned modulations. Blockade of \u03b2- or \u03b11-adrenoceptors significantly ameliorated these effects, with combined blockade yielding superior benefits. Carvedilol\u2019s effects were largely \u03b2-mediated, with minor \u03b11 involvement. Low-dose phenylephrine yielded modest improvement, supporting a context-dependent, protective role of \u03b11-adrenoceptor activation during metabolic stress. The dependence of drugs\u2019 effects on \u03b2-arrestin2 highlights its potential as a central regulator of pancreatic remodeling and a promising target in IR-linked pathologies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03946320251365089","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T12:15:18Z","timestamp":1759320918000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of \u03b2 and \u03b11-adrenoceptors in pancreatic regulation of glucose homeostasis, apoptosis, and fibrosis in dexamethasone-treated rats: A new insight into \u03b2-arrestin2 crosstalk with cAMP, PKA-ERK1\/2-CREB, and PKB-FOXO1 signaling pathways"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8637-9204","authenticated-orcid":false,"given":"Nehal S.","family":"Wahba","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Abdelfattah-Hassan","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, College of Applied and Health Sciences, A\u2019Sharqiyah University, Ibra, Sultanate of Oman"},{"name":"Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalia A.","family":"Hemead","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alaa S.","family":"Wahba","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Islam A.A.E.-H.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona F.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam A.","family":"AL-Ghamdi","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"Experimental Biochemistry Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etimad","family":"Huwait","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia"},{"name":"Experimental Biochemistry Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mostafa E.","family":"El-Naggar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Sadat City, Menoufia, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep15954"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-1499"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-13-0189"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2613.2008.00588.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/983453"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2011.06.002"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-214189"},{"key":"e_1_3_3_9_2","first-page":"3275","article-title":"Cellular signaling pathways regulating \u03b2\u2011cell proliferation as a promising therapeutic target in the treatment of diabetes","volume":"16","author":"Jiang WJ","year":"2018","unstructured":"Jiang WJ, Peng YC, Yang KM (2018) Cellular signaling pathways regulating \u03b2\u2011cell proliferation as a promising therapeutic target in the treatment of diabetes. 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