{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:49:41Z","timestamp":1791035381136,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2002,7,8]],"date-time":"2002-07-08T00:00:00Z","timestamp":1026086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2002,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Exendin\u20104 (EX\u20104), a long acting agonist of GLP\u20101, induces an endocrine phenotype in Capan\u20101 cells. Under culture conditions which include serum, \u223c10% of the cells contain insulin and glucagon. When exposed to EX\u20104 (0.1 nM, up to 5 days), the number of cells containing insulin and glucagon increased to \u223c40%. Western blot analysis detected a progressive increase in protein levels of glucokinase and GLUT2 over 3 days of EX\u20104 treatment. We explored the sequence of activation of certain transcription factors known to be essential for the beta cell phenotype: PDX\u20101, Beta2\/NeuroD, and hepatocyte nuclear factor 3\u03b2 (HNF3\u03b2). Double immunostaining showed that PDX\u20101 coexisted with insulin and glucagon in EX\u20104\u2010treated cells. Treatment caused an increase in PDX\u20101 protein levels by 24 h and induced its nuclear translocation. Beta2\/NeuroD protein levels also increased progressively over 24 h. HNF3\u03b2 protein level increased twofold as early as 6 h after EX\u20104 treatment. EMSA results indicated that EX\u20104 caused a 12\u2010fold increase in HNF3\u03b2 binding to PDX\u20101 promoter area II. Beta2\/NeuroD protein levels progressively increased after 24 h treatment. Differentiation to insulin\u2010producing cells was also seen when Capan\u20101 cells were transfected with <jats:italic>pdx\u20101<\/jats:italic>, with 80% of these cells expressing insulin 3 days after transfection. <jats:italic>PDX\u20101<\/jats:italic> antisense totally inhibited such conversion. During the differentiation of duct cells to endocrine cells, cAMP levels (EX\u20104 is a ligand for the GLP\u20101, G\u2010protein coupled receptor) and MAP kinase activity increased. Our results indicate that EX\u20104 activates adenylyl cyclase and MAP kinase which, in turn, may lead to activation of transcription factors necessary for an endocrine phenotype. 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