{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T22:46:19Z","timestamp":1761518779790},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,7,14]],"date-time":"2005-07-14T00:00:00Z","timestamp":1121299200000},"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":[[2006,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human islet\u2010derived precursor cells (hIPCs) and human pancreatic ductal carcinoma (PANC\u20101) cells can be induced to form aggregates that subsequently differentiate into hormone\u2010expressing islet\u2010like cell aggregates (ICAs). We show that challenge of hIPCs or PANC\u20101 cells with thrombin or trypsin resulted in stimulation of signaling via the inositol\u2010<jats:italic>tris<\/jats:italic>\u2010phosphate second messenger pathway leading to rapid, transient increases in cytosolic calcium ion concentration in the majority of the cells. Because we found that hIPCs, PANC\u20101 cells, human fetal pancreas, and human adult islets express two protease\u2010activated receptors (PARs), PAR\u20101 and PAR\u20102, we tested whether the effects of thrombin and trypsin were mediated, at least in part, by these receptors. Peptide agonists that are relatively specific for PAR\u20101 (SFLLRN\u2010amide) or PAR\u20102 (SLIGRL\u2010amide) stimulated increases in inositol phosphates and cytosolic calcium ion concentration, and increased the phosphorylation of <jats:italic>Rho<\/jats:italic>, a small G\u2010protein associated with cytoskeletal changes affecting cellular morphology and migration. Most importantly, we show that these agonists increased the rate of hIPC aggregation leading to the formation of more viable, smaller ICAs. Our data show that thrombin and trypsin accelerate aggregation, an early stage of hIPC differentiation in vitro, and imply that pancreatic trypsin and thrombin may be involved in islet development in vivo. J. Cell. Physiol. 206: 322\u2013328, 2006. 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