Effect of daf2 on insulin secreating cells and target cells

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(Role of daf2 on insulin-secreting cells)To examine the role of daf2 gene on insulin-secreting cells, we used the pancreatic-cells expressing daf2 gene. Previous report indicated that the mutation of daf2 induce the inhibitory effect of apoptosis in the cells. Although menin is a nuclear protein and interacts with daf2, its role in the pathogenesis of MEN 1-related endocrine tumors including insulinoma remains unknown. In this study, we examined the effects of daf2 and menin on the human insulin production. INS-1 cells were then co-transfected with the menin expression vector and a luciferase reporter gene linked to 235 bp from the rat insulin gene 5'-flanking region (pINS-LUC). Promoter activity of the insulin gene was significantly decreased in the co-transfected cells as compared to mock-transfected controls. Rat insulinoma cell line, INS-1 were transfected with the menin expression vector and stably transfected cell clones were used to examine the insulin secretion. In the cells with high level expression of menin, both insulin secretion and thymidine incorporation into DNA were inhibited as compared to mock-transfected cells. On the other hand, the rate of apoptosis of menin-transfected cells was increased as compared to mock-transfeced cells.(The role of daf2 on scavenger receptor gene expression in vascular smooth muscle cell)The secreted protein, Gas6 is encoded by the growth arrest-specific gene 6, has been originally identified as the ligand of the Axl receptor tyrosine kinase, and upregulated the expression of the class A scavenger receptor (SRA) in the pathogenesis of atherosclerosis and foam cell formation in human vascular smooth muscle cells (HVSMCs). These results indicated that daf2 induced the apoptosis in the smooth muscle cell mediated by Gas6.