{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T02:47:38Z","timestamp":1783565258666,"version":"3.55.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Diabetol"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Telmisartan is a well-established angiotensin II type 1 receptor blocker that improves insulin sensitivity in animal models of obesity and insulin resistance, as well as in humans. Telmisartan has been reported to function as a partial agonist of the peroxisome proliferator-activated receptor (PPAR) \u03b3, which is also targeted by the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase (SIRT1). Here, we investigated the pathways through which telmisartan acts on skeletal muscle, <jats:italic>in vitro<\/jats:italic> as well as <jats:italic>in vivo<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Nine-week-old male <jats:italic>db\/db<\/jats:italic> mice were fed a 60% high-fat diet, with orally administrated either vehicle (carboxymethyl-cellulose, CMC), 5 mg\/kg telmisartan, or 5 mg\/kg telmisartan and 1 mg\/kg GW9662, a selective irreversible antagonist of PPAR\u03b3, for 5 weeks. Effects of telmisartan on <jats:italic>Sirt1<\/jats:italic> mRNA, AMPK phosphorylation, and NAD+\/NADH ratio were determined in C2C12 cultured myocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results and discussion<\/jats:title>\n            <jats:p>Telmisartan treatment improved insulin sensitivity in obese <jats:italic>db\/db<\/jats:italic> mice fed a high-fat diet and led to reduction in the size of hypertrophic pancreatic islets in these mice. Moreover, <jats:italic>in vitro<\/jats:italic> treatment with telmisartan led to increased expression of <jats:italic>Sirt1<\/jats:italic> mRNA in C2C12 skeletal muscle cells; the increase in Sirt1 mRNA in telmisartan-treated C2C12 myoblasts occurred concomitantly with an increase in AMPK phosphorylation, an increase in NAD+\/NADH ratio, and increases in the mRNA levels of PGC1\u03b1, FATP1, ACO, and GLUT4.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our results indicate that telmisartan acts through a PPAR\u03b3-independent pathway, but at least partially exerts its effects by acting directly on skeletal muscle AMPK\/SIRT1 pathways.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1475-2840-11-139","type":"journal-article","created":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T23:13:54Z","timestamp":1352416434000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Telmisartan ameliorates insulin sensitivity by activating the AMPK\/SIRT1 pathway in skeletal muscle of obese db\/db mice"],"prefix":"10.1186","volume":"11","author":[{"given":"Asuka","family":"Shiota","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Shimabukuro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiju","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Soeki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsuko","family":"Uematsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotsugu","family":"Kurobe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norikazu","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Sakaue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Masuzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iichiro","family":"Shimomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Sata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,11,8]]},"reference":[{"key":"560_CR1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/nrn3209","volume":"13","author":"RH Houtkooper","year":"2012","unstructured":"Houtkooper RH, Pirinen E, Auwerx J: Sirtuins as regulators of metabolism and healthspan. 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