Abnormality of O-GlcNAcylation and pathogenesis of beta cell dysfunction
| Project/Area Number |
15K09383
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
SEKINE OSAMU 滋賀医科大学, 医学部, 助教 (00402719)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | O-GlcNAc修飾 / 膵β細胞 / インスリン分泌 / 糖尿病 / O-結合型糖修飾 / 膵臓 |
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| Outline of Final Research Achievements |
O-GlcNAcylation is characterized by the addition of N-acetylglucosamine to various proteins by O-GlcNAc transferase (OGT) as the post-translational modification and serves in sensing intracellular nutrients by modulating various cellular process. Abnormality of O-GlcNAcylation may be associated with the pathogenesis of metabolic disease such as diabetes mellitus. We investigated insulin secretion and pancreatic beta cell function using tamoxifen-inducible pancreatic beta cell-specific Ogt-KO mice. These mice displayed transient hypoglycemia associated with higher insulin secretion and accelerated adiposity (early phase), followed by subsequent hyperglycemia with insulin depletion accompanied by beta cell apoptosis (late phase). In addition, tamoxifen-inducible global Ogt-KO mice exhibited a lethal phenotype from 4 weesks post injection. These findings suggest that O-GlcNAcylation plays a crucial role in pancreatic beta cell function and survival under physiological conditions.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] O-GlcNAcylation plays a physiologically important role in glucose homeostasis in pancreatic β cells rather than in insulin target tissues2017
Author(s)
Shogo Ida, Katsutaro Morino, Osamu Sekine, Natsuko Ohashi, Shinji Kume, Tokuhiro Chano, Kanako Iwasaki, Norio Harada, Nobuya Inagaki, Satoshi Ugi, Hiroshi Maegawa
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Journal Title
Diabetologia (in press)
Volume: -
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] O-linked β-N-acetylglucosamine modification of proteins is essential for foot process maturation and survival in podocytes.2017
Author(s)
Ono S, Kume S, Yasuda-Yamahara M, Yamahara K, Takeda N, Chin-Kanasaki M, Araki H, Sekine O, Yokoi H, Mukoyama M, Uzu T, Araki SI, Maegawa H.
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Journal Title
Nephrol Dial Transplant.
Volume: 未定
Issue: 9
Pages: 000-000
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal.2015
Author(s)
Nagayama K, Morino K, Sekine O, Nakagawa F, Ishikado A, Iwasaki H, Okada T, Tawa M, Sato D, Imamura T, Nishio Y, Ugi S, Kashiwagi A, Okamura T, Maegawa H
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Journal Title
Nutrients
Volume: 7(9)
Issue: 9
Pages: 8112-8126
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Sonoda N, Morimoto A, Ugi S, Morino K, Sekine O, Nemoto K, Godai K, Maegawa H, Miyamatsu N. Predictors for Mild and Severe Hypoglycemia in Insulin-Treated Japanese Diabetic Patients.2015
Author(s)
Sonoda N, Morimoto A, Ugi S, Morino K, Sekine O, Nemoto K, Godai K, Maegawa H, Miyamatsu N
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Journal Title
PLoS One
Volume: 10(6)
Issue: 6
Pages: e0130584-e0130584
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Lack of O-GlcNAcylation Enhances Exercise-Dependent Glucose Utilization through Amp Kinase Activation in Skeletal Muscle2017
Author(s)
KOICHIRO MURATA, KATSUTARO MORINO, SHOGO IDA, NATSUKO OHASHI, HIROTAKA IWASAKI, MENGISTU LEMECHA SHUKARE, OSAMU SEKINE, SHINJI KUME, SHI YOUNG PARK, CHEOL SOO CHOI, SATOSHI UGI, HIROSHI MAEGAWA
Organizer
American Diabetes Association 77th
Related Report
Int'l Joint Research
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