{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:43:04Z","timestamp":1760240584075,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T00:00:00Z","timestamp":1563926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>With a global prevalence among adults over 18 years of age approaching 9%, Type 2 diabetes mellitus (T2DM) has reached pandemic proportions and represents a major unmet medical need. To date, no disease modifying treatment is available for T2DM patients. Accumulating evidence suggest that the sensory nervous system is involved in the progression of T2DM by maintaining low-grade inflammation via the vanilloid (capsaicin) receptor, Transient Receptor Potential Vanilloid-1 (TRPV1). In this study, we tested the hypothesis that TRPV1 is directly involved in glucose homeostasis in rodents. TRPV1 receptor knockout mice (Trpv1\u2212\/\u2212) and their wild-type littermates were kept on high-fat diet for 15 weeks. Moreover, Zucker obese rats were given the small molecule TRPV1 antagonist, N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide (BCTC), per os twice-a-day or vehicle for eight days. Oral glucose tolerance and glucose-stimulated insulin secretion was improved by both genetic inactivation (Trpv1\u2212\/\u2212 mice) and pharmacological blockade (BCTC) of TRPV1. In the obese rat, the improved glucose tolerance was accompanied by a reduction in inflammatory markers in the mesenteric fat, suggesting that blockade of low-grade inflammation contributes to the positive effect of TRPV1 antagonism on glucose metabolism. We propose that TRPV1 could be a promising therapeutic target in T2DM by improving glucose intolerance and correcting dysfunctional insulin secretion.<\/jats:p>","DOI":"10.3390\/medsci7080082","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T10:48:19Z","timestamp":1563965299000},"page":"82","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["TRPV1 Antagonists as Novel Anti-Diabetic Agents: Regulation of Oral Glucose Tolerance and Insulin Secretion Through Reduction of Low-Grade Inflammation?"],"prefix":"10.3390","volume":"7","author":[{"given":"Dorte X.","family":"Gram","sequence":"first","affiliation":[{"name":"PILA Pharma, 211 21 Malm\u00f6, Sweden"},{"name":"Former Employee, Research &amp; Development, Novo Nordisk A\/S, 2760 M\u00e5l\u00f8v, Denmark"}]},{"given":"Josefine","family":"Fribo","sequence":"additional","affiliation":[{"name":"Former Employee, Research &amp; Development, Novo Nordisk A\/S, 2760 M\u00e5l\u00f8v, Denmark"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3475-6108","authenticated-orcid":false,"given":"Istvan","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London SW7 2AZ, UK"}]},{"given":"Carsten","family":"Gotfredsen","sequence":"additional","affiliation":[{"name":"Former Employee, Research &amp; Development, Novo Nordisk A\/S, 2760 M\u00e5l\u00f8v, Denmark"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7717-7790","authenticated-orcid":false,"given":"Ana","family":"Charrua","sequence":"additional","affiliation":[{"name":"Institute of Histology and Embryology, Faculty of Medicine, University of Porto, Alameda Prof Hernani Monteiro, 4099-002 Porto, Portugal"}]},{"given":"John B.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Former Employee, Research &amp; Development, Novo Nordisk A\/S, 2760 M\u00e5l\u00f8v, Denmark"},{"name":"Concit Pharma APS, 4450 Jyderup, Denmark"}]},{"given":"Anker J.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Former Employee, Research &amp; Development, Novo Nordisk A\/S, 2760 M\u00e5l\u00f8v, Denmark"}]},{"given":"Arpad","family":"Szallasi","sequence":"additional","affiliation":[{"name":"1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,24]]},"reference":[{"key":"ref_1","unstructured":"Umpierrez, G.E. 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