{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T23:12:51Z","timestamp":1717801971256},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,9,29]],"date-time":"2014-09-29T00:00:00Z","timestamp":1411948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label \/><jats:p>Ghrelin is a physiological\u2010active peptide with growth hormone\u2010releasing activity, orexigenic activity, etc. In addition, the recent study has also suggested that ghrelin possesses the pathophysiological abilities related with type 2 diabetes. However, the ghrelin\u2010direct\u2010effects implicated in type 2 diabetes on peripheral tissues have been still unclear, whereas its actions on the central nervous system (CNS) appear to induce the development of diabetes. Thus, to assess its peripheral effects correlated with diabetes, we investigated the regulatory mechanisms about adipokines, which play a central role in inducing peripheral insulin resistance, secreted from mature 3T3\u2010L1 adipocytes stimulated with ghrelin <jats:italic>in vitro<\/jats:italic> .<\/jats:p><jats:p>The stimulation with 50\u2009nmol\/L ghrelin for 24\u2009h resulted in the significant 1.9\u2010fold increase on vascular endothelial growth factor\u2010120 (VEGF<jats:sub>120<\/jats:sub>) releases (p\u2009&lt;\u20090.01) and the 1.7\u2010fold on monocyte chemoattractant protein\u20101 (MCP\u20101) (p\u2009&lt;\u20090.01) from 3T3\u2010L1 adipocytes, respectively, while ghrelin failed to enhance tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), interleukin\u20101\u03b2 (IL\u20101\u03b2), IL\u20106, IL\u201010 and adiponectin secretions. In addition, Akt phosphorylation on Ser473 and c\u2010Jun NH<jats:sub>2<\/jats:sub>\u2010terminal protein kinase (JNK) phosphorylation on Thr183\/Tyr185 were markedly enhanced 1.4\u2010fold (p\u2009&lt;\u20090.01) and 1.6\u2010fold (p\u2009&lt;\u20090.01) in the ghrelin\u2010stimulated adipocytes, respectively. Furthermore, the treatment with LY294002\u2009(50\u2009\u03bcmol\/L) and Wortmannin (10nmol\/L), inhibitors of phosphatidylinositol 3\u2010kinase (PI3K), significantly decreased the amplified VEGF<jats:sub>120<\/jats:sub> secretion by 29% (p\u2009&lt;\u20090.01) and 28% (p\u2009&lt;\u20090.01) relative to the cells stimulated by ghrelin alone, respectively, whereas these inhibitors had no effects on increased MCP\u20101 release. On the other hand, JNK inhibitor SP600125\u2009(10\u2009\u03bcmol\/L) clearly reduced the increased MCP\u20101, but not VEGF<jats:sub>120<\/jats:sub>, release by 35% relative to the only ghrelin\u2010stimulated cells (p\u2009&lt;\u20090.01).<\/jats:p><jats:p>In conclusion, ghrelin can enhance the secretions of proinflammatory adipokines, VEGF<jats:sub>120<\/jats:sub> and MCP\u20101, but fails to affect IL\u201010 and adiponectin which are considered to be anti\u2010inflammatory adipokines. Moreover, this augmented VEGF<jats:sub>120<\/jats:sub> release is invited through the activation of PI3K pathways and the MCP\u20101 is through JNK pathways. Consequently, our results strongly suggest that ghrelin can induce the development of diabetes via its direct\u2010action in peripheral tissues as well as via in CNS. J. Cell. Physiol. 230: 199\u2013209, 2015. \u00a9 2014 The Authors. <jats:italic>Journal of Cellular Physiology<\/jats:italic> Published by Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.24699","type":"journal-article","created":{"date-parts":[[2014,6,24]],"date-time":"2014-06-24T05:59:51Z","timestamp":1403589591000},"page":"199-209","source":"Crossref","is-referenced-by-count":5,"title":["Ghrelin Augments the Expressions and Secretions of Proinflammatory Adipokines, VEGF<sub>120<\/sub> and MCP\u20101, in Differentiated 3T3\u2010L1 Adipocytes"],"prefix":"10.1002","volume":"230","author":[{"given":"Atsuko","family":"Kitahara","sequence":"first","affiliation":[{"name":"Third Department of Internal Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuto","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Third Department of Internal 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