2013 Fiscal Year Final Research Report
Analysis of Foxo1-regulated genes using Foxo1-deficient pancreatic beta cells
| Project/Area Number |
23617011
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Integrated Nutrition Science
|
|---|
| Research Institution | Mukogawa Women's University Junior College Division (2013)
Osaka University (2011-2012) |
|---|
Principal Investigator |
YAMATO Eiji 武庫川女子大学短期大学部, 食生活学科, 教授 (20273667)
|
|---|
| Project Period (FY) |
2011 – 2013
|
| Keywords | Foxo1 / 膵ベータ細胞 / インスリン分泌 / アポトーシス |
|---|
| Research Abstract |
We produced a beta-cell line with inducible Foxo1 deletion. We generated a conditional knockout mouse line, in which Cre deletes the Foxo1 gene. We then established a beta-cell line from an insulinoma induced in this knockout mouse by the beta-cell-specific expression of SV40T antigen. In this cell line, designated MIN6-Foxo1flox/flox, adenovirus-mediated Cre expression ablates the Foxo1 gene, generating MIN6-Foxo1-KO cells. Using these knockout and floxed cell lines, we found that Foxo1 ablation enhanced the glucose-stimulated insulin secretion (GSIS) at high glucose concentrations and enhanced beta-cell proliferation. We also conducted DNA microarray analyses of MIN6-Foxo1-KO cells infected with either an adenovirus vector expressing a constitutively active FOXO1 or a control vector and identified several Foxo1-regulated genes. These cells should be useful for further studies on Foxo1's roles in beta-cells and may lead to novel strategies for treatment of type 2 diabetes mellitus.
|
