Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/28341
Title: Investigation of the roles of two Rac1 effectors phosphatidylinositol-5 kinase 1a and p21-activated kinase 1 in insulin-secreting cells
Authors: ZHANG JIPING
Keywords: phosphatidylinositol-4-phosphate 5-kinase, p21-activated kinase, insulin secretion, glucotoxicity, pancreatic beta cells, Rac
Issue Date: 9-Jun-2009
Source: ZHANG JIPING (2009-06-09). Investigation of the roles of two Rac1 effectors phosphatidylinositol-5 kinase 1a and p21-activated kinase 1 in insulin-secreting cells. ScholarBank@NUS Repository.
Abstract: Rac1 has been proved to participate in glucose- and cAMP-induced insulin secretion through regulation of actin cytoskeleton previously. In my study, the knockdown of PIP5K-I alpha and PAK1, two critical downstream effectors of Rac1, was achieved by using RNA interference technique in INS-1 cells. PIP5K-I alpha knockdown disrupted F-actin structure and caused changes in glucose metabolism, membrane potential, intracellular Ca 2+ concentration and PIP2 distribution. The incremental insulin release over basal stimulated by high glucose and forskolin was inhibited in PIP5K-I alpha knockdown cells, suggesting a role of PIP5K-I alpha in both the proximal and distal steps of signaling cascades in insulin secretion. On the other hand, PAK1 knockdown had no effect on either insulin secretion or actin cytoskeleton, but rescued prolonged exposure to high glucose induced cell death and blocked activation of caspase-3 partially. P38 MAPK was activated downstream of PAK1 upon glucotoxicity and may, at least in part, mediate the pro-apoptotic role of PAK1. The latter part suggests that PAK1 is involved in control of beta-cell death and glucotoxicity.
URI: http://scholarbank.nus.edu.sg/handle/10635/28341
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