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The present study examined how the \u03b2-adrenergic receptor agonist isoprenaline (ISO) protected against DKD by regulating the cyclic GMP\u2013AMP synthase\u2013stimulator of interferon genes (cGAS\u2013STING) signaling pathway through multiple targets. In a streptozotocin-induced diabetic mouse model, ISO treatment improved glomerulosclerosis, reduced podocyte injury and proteinuria, and suppressed renal inflammation. Network pharmacology and molecular docking suggested that, besides activating ADRB1\/2, ISO may interact with AKT1, SRC, GSK3\u03b2, and EGFR, which are involved in cGAS\u2013STING signaling regulation. These findings indicate that ISO alleviates DKD by inhibiting excessive activation of the cGAS\u2013STING pathway through multi-target coordination, providing a new perspective for therapeutic development.<\/jats:p>","DOI":"10.1042\/bsr20250174","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:21:56Z","timestamp":1772986916000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isoprenaline alleviates diabetic kidney disease via multi-target inhibition of the cGAS\u2013STING pathway"],"prefix":"10.1042","volume":"46","author":[{"given":"Runtao","family":"Ma","sequence":"first","affiliation":[{"name":"1School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Song","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"2School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqi","family":"Chen","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianqi","family":"Chen","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangyao","family":"Zhu","sequence":"additional","affiliation":[{"name":"2School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingrong","family":"Pan","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengyu","family":"Ma","sequence":"additional","affiliation":[{"name":"2School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qigui","family":"Mo","sequence":"additional","affiliation":[{"name":"2School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surui","family":"Lu","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuanjie","family":"Yu","sequence":"additional","affiliation":[{"name":"3Radiology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4860-9117","authenticated-orcid":false,"given":"Yi","family":"Guo","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"2026050504013993100_B1","doi-asserted-by":"publisher","first-page":"8561","DOI":"10.1038\/s41467-025-63529-5","article-title":"Prolonged glucagon exposure rewires lipid oxidation and drives diabetic kidney disease progression","volume":"16","author":"Liu","year":"2025","journal-title":"Nat. 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