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Intensive insulin therapy for POHG is often ineffective and may even worsen patient outcomes. Non-invasive focused ultrasound stimulation (FUS) of glucose-sensing abdominal neurons improves glucose metabolism in animal models of diabetes, but its potential role in treating POHG remains unknown. In this study, we explored whether FUS of the superior mesenteric plexus (SMP) alters insulin sensitivity and post-operative fasting blood glucose (FBG) in a swine model of surgical stress-induced POHG. In each of 3 anesthetized animals, FUS targeting the porta hepatis (PH) of the liver or the SMP was delivered and insulin sensitivity was assessed in each case. In another series of experiments, 4 animals received SMP-FUS and 3 sham stimulation, after which surgical stress was induced via small bowel resection. In the 7 surgically operated animals, insulin sensitivity was measured before and after SMP-FUS (or sham), and fasting blood glucose (FBG) was measured before and 16\u00a0h after surgery. In all animals, insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp (HEC) method. Results: SMP-FUS elicits a greater increase in insulin sensitivity than PH-FUS. On the day of surgery, SMP-FUS increases insulin sensitivity, compared to sham treatment. The day after surgery, surgically operated animals develop mild hyperglycemia. SMP-FUS-treated animals have higher FBG than sham-FUS-treated animals. No clear relationship is observed between FUS-induced changes in insulin sensitivity and next-day FBG. Conclusion: While SMP-FUS improves insulin sensitivity during surgery, it may exacerbate POHG.<\/jats:p>","DOI":"10.1186\/s42234-025-00176-7","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T23:02:33Z","timestamp":1750201353000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of focused ultrasound neuromodulation of the superior mesenteric plexus on insulin sensitivity and post-operative hyperglycemia in a swine model of surgical stress"],"prefix":"10.1186","volume":"11","author":[{"given":"Weiguo","family":"Song","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaled","family":"Qanud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dane A.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jared M.","family":"Huston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3967-8164","authenticated-orcid":false,"given":"Stavros","family":"Zanos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"176_CR1","doi-asserted-by":"publisher","first-page":"892086","DOI":"10.3389\/fimmu.2022.892086","volume":"13","author":"U Ahmed","year":"2022","unstructured":"Ahmed U, Graf JF, Daytz A, Yaipen O, Mughrabi I, Jayaprakash N, Cotero V, Morton C, Deutschman CS, Zanos S, Puleo C. 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Brain Stimul. 2023;16(3):703\u201311.","journal-title":"Brain Stimul"}],"container-title":["Bioelectronic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42234-025-00176-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s42234-025-00176-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42234-025-00176-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T23:02:36Z","timestamp":1750201356000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioelecmed.biomedcentral.com\/articles\/10.1186\/s42234-025-00176-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,18]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["176"],"URL":"https:\/\/doi.org\/10.1186\/s42234-025-00176-7","relation":{},"ISSN":["2332-8886"],"issn-type":[{"value":"2332-8886","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,18]]},"assertion":[{"value":"10 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experiments were approved by the IACUC of the Feinstein Institute.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors consent for publication of this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14"}}