Elucidation of the mechanism of pancreas development and its application for the regenerative medicine
| Project/Area Number |
14571067
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
NOMURA Masatoshi Kyushu University, Hospital, Research associate, 大学病院, 助手 (30315080)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OKABE Taijirou Kyushu University, Hospital, Research associate, 大学病院, 助手 (40264030)
GOTO Kiminobu Kyushu University, Hospital, Research associate, 大学病院, 助手 (90284512)
YANASE Toshihiko Kyushu University, Graduate School of Medical Science, Associate Professor, 大学院・医学研究院, 助教授 (30239818)
NAWATA Hajime Kyushu University, Graduate School of Medical Science, Professor, 大学院・医学研究院, 教授 (10038820)
|
|---|
| Project Period (FY) |
2002 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
|---|
| Keywords | Activin / Smad2 / Pancreatic beta cell / Knock out mouse / Insulin / Transgenic mouse / ノックアウトマウス / Smad / アクチビン受容体 / ES細胞 |
|---|
| Research Abstract |
1) Pancreas beta cell-specific gene disruption of Smad2 in mice
To investigate the role of Smad2 in pancreatic β cells, we have used the Cre-loxP system to specifically disrupt Smad2 gene in the β cells. We crossed the mice homozygous for a floxed allele of Smad2 (Smad2^<loxC/loxC>) with Ins-Cre mice that express the Cre recombinase under the control of the rat insulin promoter to obtain Smad2^<loxC/loxC>Ins-Cre (Smad2βKO).
Smad2βKO mice show a defective insulin secretion in response to glucose and a progressive impairment of glucose tolerance. Interestingly, histological analysis revealed that pancreas islets in Smad2βKO were bigger that those in control littermates, suggesting that Smad2 is involved in not only insulin secretion but also proliferation of β cells.
2) Conditional expression of activin type IB receptor in pancreas β cells in mice.
We first generated the transgenic mice carrying a transgene construct in which green fluorescence protein (GFP) gene flanked by directly repeated
… More
loxP sequences was placed under the control of chicken β-actin promoter and followed by the constitutive active form of activin type IB receptor (ActRIBCA) gene and an IRES βgeo cassette (ActRIBCATg). The transgene directs the expression of ActRIBCA upon the Cre-mediated excision of the loxP-flanked GFP gene. To achieve R cell specific ActRIBCA transgenic mouse (ActRIBCAβS-Tg), we crossed ActRIBCATg mice with Ins-Cre mice. The resultant mice exhibited a defective insulin secretion in response to glucose and a progressive impairment of glucose tolerance. The electrophysiological analysis performed with isolated β cells revealed that the function of K_<ATP> channel of β cells of the mutant mice was dramatically attenuated. The impairment of insulin release in the mutant mice may be explained, at least in part, by the alteration of the function of K_<ATP> channels.
Our results suggested an important role for signaling by the ActRIB-Smad2 in both glucose sensing and insulin secretion in type 2 diabetes. Less
|
Report
(4 results)
Research Products
(15 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Publications] Zhao, Y., Goto, K., Saitoh, M., Yanase, T., Nomura, M., Okabe, T., Takayanagi, R., Nawata, H.: "Activation function-1 domain of androgen receptor contributes to the interaction between subnuclear splicing factor compartment and nuclear receptor compartment"J Biol Chem. 277. 30031-30039 (2002)
