Investigation of the mechanism of beta-cell failure in diabetes using Wolfram Syndrome as a model
| Project/Area Number |
23390080
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Yamaguchi University |
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Principal Investigator |
TANIZAWA Yukio 山口大学, 医学(系)研究科(研究院), 教授 (00217142)
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| Co-Investigator(Kenkyū-buntansha) |
OHTA Yasuharu 山口大学, 医学部, 准教授 (60448280)
TANABE Katsuya 山口大学, 医学部附属病院, 助教 (00397994)
TAGUCHI Akihiko 山口大学, 医学部, 講師 (20634744)
幡中 雅行 山口大学, 大学院・医学系研究科, 助教 (60572534)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2012: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | 糖尿病 / インスリン / アポトーシス / ストレス / 膵β細胞 / Wolfram症候群 / インスリン分泌 / 小胞体ストレス / β細胞 / ウォルフラム症候群 |
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| Research Abstract |
Wolfram syndrome is an autosomal recessive disorder characterized by insulin deficient diabetes and optic atrophy. Diabetes is caused by pancreatic b-cell apoptosis. In most patients, WFS1 gene is mutated. WFS1 gene is also a type 2 diabetes gene. We conducted a nation-wide survey for the Wolfram syndrome in Japan. In the patients, pancreatic b-cell death is caused by ER stress. In addition, beta-cells are functionally abnormal. That functional failure is at least in part, due to acidification defects inside the secretory granules. WFS1 protein exists on the secretory granule membrane, in addition to the ER membrane. In the secretory granule, it maintains intra-granular acidic milieu, that is important for "priming" of the granule exocytosis. We also studied the mechanism whereby ER stress causes b-cell apoptosis. We found that excessive Gsk-3b activity enhances ATF4 degradation leading to the apoptosis. We also studied relationship between clock genes and b-cell function.
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Report
(4 results)
Research Products
(98 results)
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[Journal Article] A sibling case of Wolfram syndrome with a novel mutation Y652X in WFS12013
Author(s)
Iwasaki N., Fukawa K., Matsuo M., Urano M., Watanabe M., Ono Y., Tanabe K., Tanizawa Y., Ogata M., Ide R., Takizawa M., Nagata S., Osawa M., Uchigata Y., Saito K.
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Journal Title
Diabetology International
Volume: 5
Issue: 2
Pages: 148-153
DOI
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Peer Reviewed
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[Journal Article] Glucose and Fatty Acids Synergize to Promote B-Cell Apoptosis through Activation of Glycogen Synthase Kinase 3β Independent of JNK Activation2011
Author(s)
Tanabe K, Liu Y, Hasan SD, Martinez SC, Cras-Méneur C, Welling CM, Bernal-Mizrachi E, Tanizawa Y, Rhodes CJ, Zmuda E, Hai T, Abumrad NA, Permutt MA
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Glucose and fatty acids synergize to promote B-cell apoptosis through activation of glycogen synthase kinase 3β independent of JNK activation2011
Author(s)
Tanabe K, Liu Y, Hasan SD, Martinez SC, Cras-Meneur C, Welling CM, Bernal-Mizrachi E, Tanizawa Y, Rhodes CJ, Zmuda E, Hai T, Abumrad NA, Permutt MA
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Journal Title
PLoS One
Volume: 26
Issue: 4
Pages: e18146-e18146
DOI
Related Report
Peer Reviewed
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[Presentation] Clock-controlled output gene Dbp is a regulator of Arnt/Hif- 1β gene expression in pancreatic islet β-cells2013
Author(s)
Tanizawa Y., Nakabayashi H., Ohta Y., Yamamoto M., Susuki Y., Taguchi A., Tanabe K., Kondo M., Hatanaka M., Nagao Y.
Organizer
EASD ISLET STUDY GROUP ANNUAL MEETING 2013 (Beta-cell Regeneration and Genome Regulation)
Place of Presentation
Barcelona, Spain
Related Report
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[Presentation] Clock-Controlled Output Gene Dbp is a Regulator of Arnt/Hif-1β Gene Expression in Pancreatic Islet β-Cells2013
Author(s)
Nakabayashi H., Ohta Y., Yamamoto M., Susuki Y., Taguchi A., Tanabe K., Kondo M., Hatanaka M., Nagao Y., Tanizawa Y
Organizer
73th Annual Meeting and Scientific Sessions of the American Diabetes Association
Place of Presentation
Chicago, IL, USA
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[Presentation] Clock-Controlled Output Gene Dbp is a Regulator of Arnt/Hif-1β Gene Expression in Pancreatic Islet β-Cells.2013
Author(s)
Nakabayashi H., Ohta Y., Yamamoto M., Susuki Y., Taguchi A., Tanabe K., Kondo M., Hatanaka M., Nagao Y., Tanizawa Y.
Organizer
73th Annual Meeting and Scientific Sessions of the American Diabetes Association
Place of Presentation
Chicago, IL, USA.
Related Report
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[Presentation] Clock-controlled output gene Dbp is a regulator of Arnt/Hif-1βgene expression in pancreatic islet β-cells.2013
Author(s)
Tanizawa Y., Nakabayashi H., Ohta Y., Yamamoto M., Susuki Y., Taguchi A., Tanabe K., Kondo M., Hatanaka M., Nagao Y.
Organizer
EASD ISLET STUDY GROUP ANNUAL MEETING 2013
Place of Presentation
Barcelona, Spain
Related Report
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[Presentation] Coock-Controlled Output Gene Dbp is a Regulator of Arnt/Hif-1βGene Expression in Pancreatic Islet β-Cells2012
Author(s)
Nakabayashi H., Ohta Y., Yamamoto M., Susuki Y., Tanabe K., Kondo M., Hatanaka M., Nagao Y., Tanizawa Y.
Organizer
The 4th Scientific Meeting of the Asian Association for the Study of Diabetes, 9th International Diabetes Federation Western Pacific Region Congress
Place of Presentation
Kyoto International Conference Center, Japan
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[Presentation] 断面調査に基づく Wolfram 症候群の実態解明2012
Author(s)
松永仁恵,田部勝也,太田康晴,奥屋 茂,和田安彦,中尾雄三,山田祐一郎,雨宮伸,杉原茂孝,岡 芳知,谷澤幸生
Organizer
第55回日本糖尿病学会年次学術集会
Place of Presentation
パシフィコ横浜
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