Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression.
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| Abstract |
Pdx-1 plays important roles both in the development of the pancreas and in maintaining pancreatic beta cell function. However, the role of Pdx-1 in the regulation of insulin release is not well established. We previously demonstrated that Pdx-1 overcomes the defect in insulin release from the insulin-producing cells derived from small hepatocytes (SHCs). Insulin secretion is regulated in vivo by the sequential events triggered by the increase of intracellular Ca(2+)-concentration in response to high glucose concentration. In the present study, we identified a new target of Pdx-1 involved in insulin release. Pdx-1 positively regulates the transcription of the gene encoding synaptotagmin 1 (Syt1) (a Ca(2+)-sensor that plays a central role in insulin release) through Pdx-1-binding sites within the 3' regulatory region of the Syt1 gene. We further demonstrated the essential role of Pdx-1 in insulin secretion by the gene knock-down strategy. Small interfering RNA (siRNA) directed against Pdx-1 specifically reduced the levels of Pdx-1 protein and Syt1 transcript in insulinoma lines. Our data indicate that Pdx-1 might contribute to the regulation of insulin release by promoting Syt1 expression in vivo, and provide useful information for future therapy of diabetes mellitus.
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| Authors | Natsuki Nakajima-Nagata, Manabu Sugai, Tomonori Sakurai, Jun-ichi Miyazaki, Yasuhiko Tabata, Akira Shimizu |
| Journal | Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 318 Issue 3 Pg. 631-5 (Jun 04 2004) ISSN: 0006-291X [Print] United States |
| PMID | 15144884 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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