{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:14:19Z","timestamp":1792174459480,"version":"4.4.0"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T00:00:00Z","timestamp":1491436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004879","name":"Collegio Ghislieri di Pavia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004879","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["17736"],"award-info":[{"award-number":["17736"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004710","name":"Fondazione Umberto Veronesi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sirtuin 6 (SIRT6) is a sirtuin family member involved in a wide range of physiologic and disease processes, including cancer and glucose homeostasis. Based on the roles played by SIRT6 in different organs, including its ability to repress the expression of glucose transporters and glycolytic enzymes, inhibiting SIRT6 has been proposed as an approach for treating type 2 diabetes mellitus (T2DM). However, so far, the lack of small\u2010molecule Sirt6 inhibitors has hampered the conduct of\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies to assess the viability of this strategy. We took advantage of a recently identified SIRT6 inhibitor, compound 1, to study the effect of pharmacological Sirt6 inhibition in a mouse model of T2DM (\n                    <jats:italic>i.e.,<\/jats:italic>\n                    in high\u2010fat\u2010diet\u2013fed animals). The administration of the Sirt6 inhibitor for 10 d was well tolerated and improved oral glucose tolerance, it increased the expression of the glucose transporters GLUT1 and \u20104 in the muscle and enhanced the activity of the glycolytic pathway. Sirt6 inhibition also resulted in reduced insulin, triglycerides, and cholesterol levels in plasma. This study represents the first\n                    <jats:italic>in vivo<\/jats:italic>\n                    study of a SIRT6 inhibitor and provides the proof\u2010of\u2010concept that targeting SIRT6 may be a viable strategy for improving glycemic control in T2DM.\u2014Sociali, G., Magnone, M., Ravera, S., Damonte, P., Vigliarolo, T., Von Holtey, M., Vellone, V. G., Millo, E., Caffa, I., Cea, M., Parenti, M. D., Del Rio, A., Murone, M., Mostoslavsky, R., Grozio, A., Nencioni, A., Bruzzone S. Pharmacological Sirt6 inhibition improves glucose tolerance in a type 2 diabetes mouse model. FASEB J. 31, 3138\u20133149 (2017).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201601294r","type":"journal-article","created":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T22:24:56Z","timestamp":1491517496000},"page":"3138-3149","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Pharmacological Sirt6 inhibition improves glucose tolerance in a type 2 diabetes mouse model"],"prefix":"10.1096","volume":"31","author":[{"given":"Giovanna","family":"Sociali","sequence":"first","affiliation":[{"name":"Section of Biochemistry Department of Experimental Medicine Center of Excellence for Biomedical Research (CEBR) University of Genova Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Magnone","sequence":"additional","affiliation":[{"name":"Section of Biochemistry Department of Experimental Medicine Center of Excellence for Biomedical Research (CEBR) University of Genova Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Ravera","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory Department of Pharmacy University of Genova Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Damonte","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Genova Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Vigliarolo","sequence":"additional","affiliation":[{"name":"Section of Biochemistry Department of Experimental Medicine Center of Excellence for Biomedical Research (CEBR) University of Genova Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Von Holtey","sequence":"additional","affiliation":[{"name":"Debiopharm International S.A. Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio G.","family":"Vellone","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences and Integrated Diagnostics University of Genova Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Millo","sequence":"additional","affiliation":[{"name":"Section of Biochemistry Department of Experimental Medicine Center of Excellence for Biomedical Research (CEBR) University of Genova Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Caffa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Genova Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Genova Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Daniele Parenti","sequence":"additional","affiliation":[{"name":"Institute of Organic Synthesis and Photoreactivity (ISOF) National Research Council (CNR) Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Del Rio","sequence":"additional","affiliation":[{"name":"Institute of Organic Synthesis and Photoreactivity (ISOF) National Research Council (CNR) Bologna Italy"},{"name":"Innovamol Srls Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilien","family":"Murone","sequence":"additional","affiliation":[{"name":"Debiopharm International S.A. 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