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Secretagogin affects insulin secretion in pancreatic beta-cells by regulating actin dynamics and focal adhesion

Title
Secretagogin affects insulin secretion in pancreatic beta-cells by regulating actin dynamics and focal adhesion
Authors
Yang, Seo-YunLee, Jae-JinLee, Jin-HeeLee, KyungeunOh, Seung HoonLim, Yu-MiLee, Myung-ShikLee, Kong-Joo
Ewha Authors
이공주
SCOPUS Author ID
이공주scopus
Issue Date
2016
Journal Title
BIOCHEMICAL JOURNAL
ISSN
0264-6021JCR Link1470-8728JCR Link
Citation
vol. 473, pp. 1791 - 1803
Keywords
actincalcium-binding proteinfocal adhesioninsulin secretionsecretagogin
Publisher
PORTLAND PRESS LTD
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Secretagogin (SCGN), a Ca2+-binding protein having six EF-hands, is selectively expressed in pancreatic beta-cells and neuroendocrine cells. Previous studies suggested that SCGN enhances insulin secretion by functioning as a Ca2+-sensor protein, but the underlying mechanism has not been elucidated. The present study explored the mechanism by which SCGN enhances glucose-induced insulin secretion in NIT-1 insulinoma cells. To determine whether SCGN influences the first or second phase of insulin secretion, we examined how SCGN affects the kinetics of insulin secretion in NIT-1 cells. We found that silencing SCGN suppressed the second phase of insulin secretion induced by glucose and H2O2, but not the first phase induced by KCl stimulation. Recruitment of insulin granules in the second phase of insulin secretion was significantly impaired by knocking down SCGN in NIT-1 cells. In addition, we found that SCGN interacts with the actin cytoskeleton in the plasma membrane and regulates actin remodelling in a glucose-dependent manner. Since actin dynamics are known to regulate focal adhesion, a critical step in the second phase of insulin secretion, we examined the effect of silencing SCGN on focal adhesion molecules, including FAK (focal adhesion kinase) and paxillin, and the cell survival molecules ERK1/2 (extracellular-signal-regulated kinase 1/2) and Akt. We found that glucose-and H2O2-induced activation of FAK, paxillin, ERK1/2 and Akt was significantly blocked by silencing SCGN. We conclude that SCGN controls glucose-stimulated insulin secretion and thus may be useful in the therapy of Type 2 diabetes.
DOI
10.1042/BCJ20160137
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약학대학 > 약학과 > Journal papers
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