Secretagogin affects insulin secretion in pancreatic β-cells by regulating actin dynamics and focal adhesion
- Secretagogin affects insulin secretion in pancreatic β-cells by regulating actin dynamics and focal adhesion
- 이경은; Seo-Yun Yang; Jae-Jin Lee; Jin-Hee Lee; Seung Hoon Oh; Yu-Mi Lim; Myung-Shik Lee; Kong-Joo Lee
- actin; calcium-binding protein; focal adhesion; insulin secretion; secretagogin
- Issue Date
- The Biochemical journal
- VOL 473, NO 12-1803
- Secretagogin (SCGN), a Ca2+ -binding protein having six EF-hands, is selectively expressed in pancreatic β-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.
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