{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:17:44Z","timestamp":1765545464845},"reference-count":43,"publisher":"American Diabetes Association","issue":"7","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,7,1]]},"abstract":"<jats:p>Type 2 diabetes results from progressive pancreatic \u03b2-cell dysfunction caused by chronic insulin resistance. Activation of c-Jun NH2-terminal kinase (JNK) inhibits insulin signaling in cultured cells and in vivo and thereby promotes insulin resistance. Conversely, the peroxisome proliferator\u2013activated receptor (PPAR) \u03b3 synthetic ligands thiazolidinediones (TZDs) enhance insulin sensitivity. Here, we show that the TZDs rosiglitazone and troglitazone inhibit tumor necrosis factor-\u03b1\u2013induced JNK activation in 3T3-L1 adipocytes. Our results indicate that PPAR\u03b3 mediates this inhibitory action because 1) it is reproduced by other chemically unrelated PPAR\u03b3 agonist ligands and blocked by PPAR\u03b3 antagonists; 2) it is enhanced by PPAR\u03b3 overexpression; and 3) it is abrogated by PPAR\u03b3 RNA interference. In addition, we show that rosiglitazone inhibits JNK activation and promotes the survival of pancreatic \u03b2-cells exposed to interleukin-1\u03b2. In vivo, the abnormally elevated JNK activity is inhibited in peripheral tissues by rosiglitazone in two distinct murine models of obesity. Moreover, rosiglitazone fails to enhance insulin-induced glucose uptake in primary adipocytes from ob\/ob JNK1\u2212\/\u2212 mice. Accordingly, we demonstrate that the hypoglycemic action of rosiglitazone is abrogated in the diet-induced obese JNK1-deficient mice. In summary, we describe a novel mechanism based on targeting the JNK signaling pathway, which is involved in the hypoglycemic and potentially in the pancreatic \u03b2-cell protective actions of TZDs\/PPAR\u03b3.<\/jats:p>","DOI":"10.2337\/db06-1293","type":"journal-article","created":{"date-parts":[[2007,6,27]],"date-time":"2007-06-27T16:33:45Z","timestamp":1182962025000},"page":"1865-1871","update-policy":"http:\/\/dx.doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":49,"title":["Hypoglycemic Action of Thiazolidinediones\/Peroxisome Proliferator\u2013Activated Receptor \u03b3 by Inhibition of the c-Jun NH2-Terminal Kinase Pathway"],"prefix":"10.2337","volume":"56","author":[{"given":"Julieta","family":"Di\u0301az-Delfi\u0301n","sequence":"first","affiliation":[{"name":"From the Institute for Research in Biomedicine, Scientific Park of Barcelona, and the Department of Biochemistry and Molecular Biology (Pharmacy), University of Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mo\u0300nica","family":"Morales","sequence":"additional","affiliation":[{"name":"From the Institute for Research in Biomedicine, Scientific Park of Barcelona, and the Department of Biochemistry and Molecular Biology (Pharmacy), University of Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carme","family":"Caelles","sequence":"additional","affiliation":[{"name":"From the Institute for Research in Biomedicine, Scientific Park of Barcelona, and the Department of Biochemistry and Molecular Biology (Pharmacy), University of Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031208183100800_R1","unstructured":"Scheen AJ: Obesity and diabetes. 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