Effect of type 2 diabetes susceptibility gene Kcnq1 gene region on pancreatic beta cells
| Project/Area Number |
26461382
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| Research Institution | Kobe University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 膵β細胞 / 2型糖尿病感受性遺伝子 / エピジェネティクス / 膵β細胞不全 / Kcnq1ot1 / 2型糖尿病 / インプリンティング |
|---|
| Outline of Final Research Achievements |
Numerous susceptibility genes for type 2 diabetes, including KCNQ1, have been identified in humans by genome-wide analyses and other studies. Experiments with genetically modified mice have also implicated various genes in the pathogenesis of diabetes. However, possible parent-of-origin effects for diabetes susceptibility alleles on disease onset have remained unclear. Here, we show that a mutation at the Kcnq1 locus reduces pancreatic β cell mass in mice via epigenetic modulation only when it is paternally inherited. The noncoding RNA Kcnq1ot1 is expressed from the Kcnq1 locus and regulates the expression of neighboring genes on the paternal allele. We found that disruption of Kcnq1 results in reduced Kcnq1ot1 expression and increased Cdkn1c expression, an imprinted gene encoding a cell cycle inhibitor, only when the mutation is on the paternal allele. Furthermore, histone modification of the Cdkn1c promoter in pancreatic islets was found to contribute to this phenomenon.
|
Report
(4 results)
Research Products
(21 results)
-
[Journal Article] Dietary Mung Bean Protein Reduces Hepatic Steatosis, Fibrosis, and Inflammation in Male Mice with Diet-Induced, Nonalcoholic Fatty Liver Disease.2017
Author(s)
Watanabe H, Inaba Y, Kimura K, Asahara SI, Kido Y, Matsumoto M, Motoyama T, Tachibana N, Kaneko S, Kohno M, Inoue H*.
-
Journal Title
J Nutr.
Volume: 147
Issue: 1
Pages: 52-60
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] Centra insulin-action activates Kupffer cells by suppressing hepatic vagal activation through nicotinic alpha 7 acetylcholine receptor.2016
Author(s)
Kimura K, Tanida M, Nagata N, Inaba Y, Watanabe H, Nagashimada M, Ota T, Asahara S, Kido Y, Matsumoto M, Toshinai K, Nakazato M, Shibamoto T, Kaneko S, Kasuga M, Inoue H
-
Journal Title
Cell reports
Volume: 14
Issue: 10
Pages: 2362-2374
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Paternal allelic mutation at the Kcnq1 locus reduces pancreatic β cell mass via epigenetic modification of Cdkn1c.2015
Author(s)
Asahara S, Etoh H, Inoue H, Teruyama K, Shibutani Y, Ihara Y, Kawada Y, Bartolome A, Hashimoto N, Matsuda T, Koyanagi-Kimura M, Kanno A, Hirota Y, Hosooka T, Nagashima K, Nishimura W, Inoue H, Matsumoto M, Higgins MJ, Yasuda K, Inagaki N, Seino S, Kasuga M, Kido Y.
-
Journal Title
Proceedings of the National Acaddemy of Scienceof the United States of America
Volume: 112(27)
Issue: 27
Pages: 8332-8337
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Regulation of pancreatic β cell mass by cross-interaction between CCAAT enhancer binding protein β induced by endoplasmic reticulum stress and AMP-activated protein kinase activity.2015
Author(s)
Matsuda T, Takahashi H, Mieda Y, Shimizu S, Kawamoto T, Matsuura Y, Takai T, Suzuki E, Koyanagi-Kimura M, Asahara S, Bartolome A, Yokoi N, Inoue H, Ogawa W, Seino S, Kido Y
-
Journal Title
PLoS ONE
Volume: 10
Issue: 6
Pages: e0130757-e0130757
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Pancreatic β cell failure mediated by mTORC1 hyperactivity and autophagic impairment.2014
Author(s)
Bartolome A, Kimura-Koyanagi M, Asahara SI, Guillen C, Inoue H, Teruyama K, Shimizu S, Kanno A, Garcia-Aguilar A, Koike M, Uchiyama Y, Benito M, Noda T, Kido Y
-
Journal Title
Diabetes
Volume: 未定
Issue: 9
Pages: 2996-3008
DOI
NAID
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
