{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:21:19Z","timestamp":1787721679461,"version":"build-2784847793"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Semaglutide is effective for type 2 diabetes mellitus (T2DM) but limited by dose-dependent gastrointestinal adverse effects. As electroacupuncture (EA) possesses glucose-lowering effects, this study investigates the therapeutic potential and mechanism of combining EA with semaglutide to facilitate dose reduction while maintaining efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice were divided into: the model group(T2DM), the high\/normal\/low-dose semaglutide group (SH, SN, SL), the normal\/low-dose semaglutide + EA at ST25 group (ST25N, ST25L), and the EA at ST25 group (ST25). The\n                      <jats:italic>db\/m<\/jats:italic>\n                      mice served as the control group (CON). Blood glucose regulation was assessed via random\/fasting blood glucose and oral glucose tolerance test (OGTT). To evaluate glycemic control and lipid profiles, HbA1c and insulin levels were quantified via ELISA, and T-CHO, TG, LDL-C, and HDL-C via biochemical kits. GLP-1R expression and \u03b2-cell abundance were assessed by immunofluorescence, and pancreatic apoptosis by TUNEL staining. PKA, pPKA, Bcl-2, Bax, and GLP-1R were analyzed by Western blot. Male Sprague\u2013Dawley (SD) rats were separated into 2 groups: the normal-dose semaglutide rats group (RSN) and the normal-dose semaglutide + EA at ST25 rats group (RST25N). LC-MS\/MS was employed to measure the concentrations of semaglutide in the plasma and pancreas, thereby evaluating the influence of EA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EA enhances the effects of semaglutide on improving glycemic control and lipid metabolism, with significant reductions in random\/fasting blood glucose, HbA1c, TCHO, TG and LDL-C levels, improvements in OGTT, insulin and HDL-C levels, and longer duration of controlled blood glucose within the target range, Furthermore, EA combined with semaglutide showed a marked increase in pancreatic \u03b2-cells, with the increased expression of pancreatic GLP-1R, PKA, pPKA and Bcl-2, the reduced expression of Bax, increased concentration of semaglutide in plasma and pancreas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>EA combined with normal- or low-dose semaglutide achieved glycemic control comparable to, or even better than, high-dose semaglutide alone, and its mechanism may be related to its enhancement of GLP-1R to inhibit \u03b2-cell apoptosis and the increased concentration of semaglutide in plasma and pancreas. EA thus has great potential to reduce the dose of semaglutide to alleviate its side effects while ensuring its clinical efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1880819","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:52:30Z","timestamp":1787719950000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Electroacupuncture enables semaglutide dose sparing in type 2 diabetes by boosting drug concentration and suppressing \u03b2-cell apoptosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinyi","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayue","family":"Wu","sequence":"additional","affiliation":[{"name":"Key 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