{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:52:35Z","timestamp":1792785155250,"version":"4.5.0"},"reference-count":34,"publisher":"Georg Thieme Verlag KG","funder":[{"name":"Shanghai Science and Technology Innovation Action\n                        Plan","award":["20ZR1470100"],"award-info":[{"award-number":["20ZR1470100"]}]},{"name":"National Natural Science Foundation\n                        of China","award":["82104257"],"award-info":[{"award-number":["82104257"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Insulin resistance is a central pathological feature underlying various\n                        metabolic disorders, involving complex mechanisms and multi-organ\n                        dysfunction. This study investigates the role of the acute-phase protein\n                        orosomucoid in systemic glucose homeostasis.<\/jats:p>\n                  <jats:p>This study utilized high-fat diet\u2013induced obese mice to model insulin\n                        resistance. The genetic deletion of orosomucoid 1 was applied, and the\n                        metabolic effects of exogenous orosomucoid administration were examined.\n                        Molecular analysis included assessing protein kinase B phosphorylation. The\n                        dependency of observed benefits on specific receptors was tested using\n                        pharmacological inhibition of C\u2013C chemokine receptor type 5 and evaluation\n                        of the leptin receptor\u2019s role.<\/jats:p>\n                  <jats:p>We demonstrate that genetic deletion of orosomucoid 1 induces insulin\n                        resistance, whereas exogenous orosomucoid administration improves glucose\n                        tolerance and insulin sensitivity in high-fat diet mice. At the molecular\n                        level, orosomucoid augments insulin-induced protein kinase B\n                        phosphorylation. Notably, these metabolic benefits are independent of the\n                        leptin receptor but are critically dependent on the C\u2013C chemokine receptor\n                        type 5, as demonstrated by pharmacological inhibition.<\/jats:p>\n                  <jats:p>Our findings establish orosomucoid as an endogenous insulin sensitizer via\n                        the C\u2013C chemokine receptor type 5\/protein kinase B pathway, coordinately\n                        ameliorating insulin resistance across multiple metabolic organs and\n                        highlighting its therapeutic potential as a novel target for metabolic\n                        disorders.<\/jats:p>","DOI":"10.1055\/a-2958-3521","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:33:12Z","timestamp":1790897592000},"source":"Crossref","is-referenced-by-count":0,"title":["Orosomucoid Enhances Insulin Sensitivity via the C\u2013C Chemokine\n                    Receptor Type 5\/Protein Kinase B Axis"],"prefix":"10.1055","author":[{"given":"Pengyuan","family":"Wang","sequence":"first","affiliation":[{"name":"Naval Medical University, China","place":["Shanghai"],"department":["Department of Clinical Pharmacy, School of Pharmacy"]},{"name":"No. 981 Hospital of the PLA, Hebei, China","place":["Chengde"],"department":["Department of Gastroenterology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Sun","sequence":"first","affiliation":[{"name":"Naval Medical University, China","place":["Shanghai"],"department":["Department of Clinical Pharmacy, School of Pharmacy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0566-9718","authenticated-orcid":false,"given":"Xia","family":"Liu","sequence":"additional","affiliation":[{"name":"Naval Medical University, China","place":["Shanghai"],"department":["Department of Clinical Pharmacy, School of Pharmacy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41392-022-01073-0","article-title":"Trends in insulin resistance: insights into mechanisms and therapeutic\n                    strategy","volume":"7","author":"M Li","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1118848","DOI":"10.3389\/fendo.2023.1118848","article-title":"Pharmacological approaches to the prevention of type 2 diabetes mellitus","volume":"14","author":"P Majety","year":"2023","journal-title":"Front Endocrinol"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1146\/annurev-physiol-031620-095920","article-title":"Effects of SGLT2 inhibitors on kidney and cardiovascular function","volume":"83","author":"V 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