Yang, Seo-Yun Lee, Jae-Jin Lee, Jin-Hee Lee, Kyungeun Oh, Seung Hoon Lim, Yu-Mi Lee, Myung-Shik Lee, Kong-Joo 2024-01-20T04:02:10Z 2024-01-20T04:02:10Z 2021-09-05 2016-06-15 0264-6021 https://pubs.kist.re.kr/handle/201004/123960 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. English PORTLAND PRESS LTD CALCIUM EXOCYTOSIS POLYMERIZATION NEUROENDOCRINE CYTOSKELETON MECHANISMS ISLET IDENTIFICATION INVOLVEMENT EXPRESSION Secretagogin affects insulin secretion in pancreatic beta-cells by regulating actin dynamics and focal adhesion Article 10.1042/BCJ20160137 1 BIOCHEMICAL JOURNAL, v.473, pp.1791 - 1803 BIOCHEMICAL JOURNAL 473 1791 1803 scie scopus 000377992700012 2-s2.0-84975167686 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article CALCIUM EXOCYTOSIS POLYMERIZATION NEUROENDOCRINE CYTOSKELETON MECHANISMS ISLET IDENTIFICATION INVOLVEMENT EXPRESSION actin calcium-binding protein focal adhesion insulin secretion secretagogin