Analysis of protein kinases relating to glucotoxicity
| Project/Area Number |
21770144
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Functional biochemistry
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| Research Institution | Kagawa University |
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Principal Investigator |
SUEYOSHI Noriyuki Kagawa University, 農学部, 准教授 (90346635)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | 糖尿病 / 糖毒性 / プロテインキナーゼ / CaMKIV / マルチPK抗体 / 2型糖尿病 / Calpain |
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| Research Abstract |
Glucotoxicity is a critical component of the pathophysiology of type 2 diabetes mellitus ; however, the molecular mechanisms of glucotoxicity are still not fully understood. In this study, we analyzed the protein kinase that correlated with insulin synthesis in INS-1 cells under glucotoxic conditions. When expression patterns of protein kinases in INS-1 cells were analyzed by Western blotting with Multi-PK antibodies, a kinase of 63 kd was significantly reduced concomitant with the decrease of insulin secretion under glucotoxic conditions. Judging from the molecular size of a native kinase/cyanogen bromide fragment and pI value, the 63-kd protein kinase was deduced to be CaMKIV. The decreased CaMKIV levels under glucotoxic conditions recovered to original levels after changing the medium to a normal glucose concentration. Recombinant CaMKIV was degraded in a Ca^<2+>-dependent manner by incubation with cell lysates from INS-1 cells under glucotoxic conditions, and degradation was protected by calpain inhibitor. Furthermore, CaMKIV was reduced in the pancreatic islets of diabetic Otsuka Long-Evans Tokushima fatty rats, whereas that of nondiabetic Long-Evans Tokushima Otsuka rats was not. This study suggests that the abnormal regulation of CaMKIV is a component of β-cell dysfunction caused by high glucose.
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Report
(3 results)
Research Products
(59 results)
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[Journal Article] The DNA-binding activity of mouse DNA methyltransferase 1 is regulated by phosphorylation with casein kinase 1delta/epsilon.2010
Author(s)
Sugiyama Y., Hatano N., Sueyoshi N., Suui N., Su N., SuN., Suuuuu N., Suetake I., Tajima S., Kinoshita E., Kinoshita-Kikuta E., Koike T., Kameshita I.
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Journal Title
Biochemical Journal 427(3)
Pages: 489-497
Related Report
Peer Reviewed
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[Journal Article] Ca^2+/calmodulin-dependent protein kinase phosphatase (CaMKP) is indispensable for normal embryogenesis in zebrafish, Danio rerio.2009
Author(s)
Sueyoshi, N., Nimura, T., Ishida, A., Taniguchi, T., Yoshimura, Y., Ito, M., Shigeri, Y., Kameshita, I.
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Journal Title
Arch.Biochem.Biophys. 488
Pages: 48-59
Related Report
Peer Reviewed
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[Journal Article] Novel Ca^2+/calmodulin-dependent protein kinase expressed in actively growing mycelia of the basidiomycetous mushroom Coprinus cinereus.2009
Author(s)
Kaneko, K., Yamada, Y., Sueyoshi, N., Watanabe, A., Asada, Y., Kameshita, I.
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Journal Title
Biochim.Biophys.Acta 1790
Pages: 71-79
Related Report
Peer Reviewed
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[Journal Article] Mechanistic insights into the hydrolysis and synthesis of ceramide by neutral ceramidase.2009
Author(s)
Inoue, T., Okino, N., Kakuta, Y., Hijikata, A., Okano, H., Goda, H.M., Tani, M., Sueyoshi, N., Kambayashi, K., Matsumura, H., Kai, Y., Ito, M.
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Journal Title
J.Biol.Chem. 284
Pages: 9566-9577
Related Report
Peer Reviewed
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