{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:45:57Z","timestamp":1791297957524,"version":"4.1.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Glucose-dependent insulinotropic polypeptide (GIP) acts as a glucose-dependent growth factor for beta-cells. Here we show that GIP and glucose also act synergistically as anti-apoptotic factors for beta-cells, using the well-differentiated beta-cell line, INS-1. Mitogenic and anti-apoptotic signaling of GIP were dependent upon pleiotropic activation of protein kinase A (PKA)\/cAMP regulatory element binder (CREB), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-kinase)\/PKB signaling modules. The signaling modules activated by GIP were dependent on glucose metabolism and calcium influx and were tightly linked by multiple activating and inhibiting cross-talk. These interactions included: (i) a central role of tyrosine phosphorylation for stimulation of PKA\/CREB, MAPK and PI3-kinase\/PKB, (ii) inhibition of PKA\/CREB by the MAPK pathway at the level of MAPK kinase-1 or downstream, (iii) activation of MAPK signaling by PI3-kinase and PKA at the level of extracellular-signal regulated kinase 1\/2 or upstream, and (iv) activation of PKB by MAPK and PKA signaling at the level of PKB or upstream. Furthermore, we demonstrated inhibition of CREB signaling by Ca(2+)\/calmodulin kinase I\/IV. These results indicated that GIP acts as a mitogenic and anti-apoptotic factor for beta-cells by pleiotropic activation of tightly linked signaling pathways in beta-cells.<\/jats:p>","DOI":"10.1677\/joe.0.1740233","type":"journal-article","created":{"date-parts":[[2004,12,2]],"date-time":"2004-12-02T18:42:13Z","timestamp":1102012933000},"page":"233-246","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":154,"title":["Mechanisms of mitogenic and anti-apoptotic signaling by glucose-dependent insulinotropic polypeptide in beta(INS-1)-cells"],"prefix":"10.1530","volume":"174","author":[{"given":"A","family":"Trumper","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Trumper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Horsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/174\/2\/233.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.bioscientifica.com\/joe\/article-pdf\/174\/2\/233\/109997\/233.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/joe\/article-pdf\/174\/2\/233\/109997\/233.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T10:56:02Z","timestamp":1783508162000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/joe\/article\/174\/2\/233\/20286\/Mechanisms-of-mitogenic-and-anti-apoptotic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,8,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2002,8,1]]}},"URL":"https:\/\/doi.org\/10.1677\/joe.0.1740233","relation":{},"ISSN":["1479-6805","0022-0795"],"issn-type":[{"value":"1479-6805","type":"electronic"},{"value":"0022-0795","type":"print"}],"subject":[],"published":{"date-parts":[[2002,8,1]]}}}