{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T14:20:14Z","timestamp":1764771614544,"version":"3.46.0"},"reference-count":149,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Administration of Traditional Chinese Medicine","award":["ZYYCXTD-C-202209"],"award-info":[{"award-number":["ZYYCXTD-C-202209"]}]},{"name":"Sichuan Provincial Administration of TCM","award":["2024zd031"],"award-info":[{"award-number":["2024zd031"]}]},{"name":"Sichuan Provincial Key Laboratory for TCM Regulation of Metabolic Diseases","award":["SZKF202201"],"award-info":[{"award-number":["SZKF202201"]}]},{"name":"Shaanxi Provincial Administration of TCM","award":["2022-ZY-SYS-002"],"award-info":[{"award-number":["2022-ZY-SYS-002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Achieving physiological glucose homeostasis in insulin-deficient diabetes remains challenging because exogenous insulin and devices cannot recapitulate the real-time, glucose-responsive secretion of pancreatic \u03b2-cells. This review aims to delineate the conceptual framework and recent advances in regulating insulin expression and release through gene- and cell-based therapies, emphasizing strategies that approximate native \u03b2-cell dynamics. We summarize progress in glucose-responsive insulin gene expression in hepatocytes, skeletal muscle, intestinal K\/L cells, and residual pancreatic \u03b2-cells via synthetic promoters and circuit engineering that couple metabolic cues to transcription. We then evaluate rapid-release platforms that uncouple biosynthesis from secretion. These include endoplasmic reticulum retention\u2014release switches and engineered vesicle-based exocytosis modules that, when actuated by metabolic, optical, electrical, or small-molecule cues, reproduce first-phase\u2014like insulin kinetics. Finally, we highlight synthetic-biology frameworks integrating chemical, metabolic, optical, electrical, and magnetic inputs to program autonomous and reversible insulin output. We conclude with a focused translational agenda: strengthen biosafety and genetic stability; induce immune tolerance and alleviate reticulum retention stress; ensure durable, tissue-specific expression; standardize non-viral\/viral delivery systems for scalable manufacturing; and integrate molecular circuits with continuous glucose monitors to achieve closed-loop, hypoglycemia-safe control. These priorities will accelerate clinical translation toward intelligent, patient-tailored insulin therapy.<\/jats:p>","DOI":"10.1093\/ejendo\/lvaf231","type":"journal-article","created":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T12:52:11Z","timestamp":1763211131000},"page":"R57-R70","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of insulin expression and release in gene and cell therapy of insulin-deficient diabetes"],"prefix":"10.1093","volume":"193","author":[{"given":"Lifang","family":"Xie","sequence":"first","affiliation":[{"name":"National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University , Chengdu, Sichuan 610064 ,","place":["PR China"]},{"name":"Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University , Hefei, Anhui 230601 ,","place":["PR China"]},{"name":"Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University , Hefei 230601 ,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanling","family":"Lu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University , Chengdu, Sichuan 610064 ,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Physics, The Chinese University of Hong Kong, Shatin , New Territories, Hong Kong SAR 999077 ,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhan","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University , Chengdu, Sichuan 610064 ,","place":["PR 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