Determine the molecular mechanism of insulin gene expression for the regeneration of pancreatic islets
| Project/Area Number |
15590944
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kagawa University |
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Principal Investigator |
ISHIDA Toshihiko Kagawa University, faculty of Medicine, First Department of Internal Medicine, Professor, 医学部, 教授 (50159737)
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| Co-Investigator(Kenkyū-buntansha) |
MURAO Koji Kagawa University, Faculty of Medicine, Assistant Professor, 医学部附属病院, 助手 (20291982)
TOKUMITSU Hiroshi Kagawa University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (20237077)
YOSHITAKA Sayo Kagawa University, Faculty of Medicine, Assistant Professor, 医学部附属病院, 助手 (20343311)
OHNISHI Hiroaki Kagawa University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (90223891)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | insulin / Diabetes Mellitus / glucose / CaMKK / CaMKIV / PREB / IB1 / IB-1 |
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| Research Abstract |
A number of factors have been reported to affect insulin synthesis in beta-cells. Although glucose is the most important regulator of insulin gene expression in pancreatic beta-cells, the mechanisms whereby glucose stimulates insulin gene transcription in response to changes in glucose concentration have not been clarified yet. In this study, we examined the role of the Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaM-K) cascade in transcriptional activation of insulin. RT-PCR, Western blotting, and immunohistochemical staining analysis revealed that CaM-K kinase-alpha (CaM-KKalpha) and CaM-KIV were localized in rat pancreatic beta-cells and their cell line, INS-1. Exposure of INS-1 cells to 11.2 mmol/l glucose elicited an increase of insulin promoter activity as well as upregulation of CaM-KIV activity within 2 min after stimulation. We investigated the influence on insulin promoter activity of the constitutively active form (CaM-KIVc) or dominant-negative mutant (CaM-KIVdn) of CaM-KIV in transfected INS-1 cells. CaM-KIVc alone was sufficient, and the upstream kinase, CaM-KK, was enhanced to upregulate the insulin promoter activity in INS-1 cells. Furthermore, cotransfection of CaM-KIVdn suppressed to a significant degree the glucose-upregulated activity of the insulin promoter. Taken together, these results indicated that the CaM-KK/CaM-KIV cascade might play an important role in glucose-upregulated transcriptional activation of the insulin gene. We have also determined the role of PREB and IB 1 as a transcriptional factor for insulin gene transcription.
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Report
(3 results)
Research Products
(19 results)
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[Journal Article] TRH-stimulated TSH expression involves Islet-Brain-1/c-Jun N-terminal Kinase Interacting protein-1.2004
Author(s)
Abe H, Murao K, Imachi H, Cao WM, Yu X, Yoshida K, Wong NCW, Shupnik MA, Haefliger JA, Waeber G, Ishida T.
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Journal Title
Endocrinology 145
Pages: 5623-5628
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Insulin like growth factor-I Regulation of hepatic scavenger receptor class BI2004
Author(s)
Cao WM, Murao K, Imachi H, Yu X, Dobashi H, Yoshida K, Muraoka T, Kotsuna N, Nagao S, Wong NCW, Ishida T.
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Journal Title
Endocrinology 145
Pages: 5540-5547
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] The role of calcium/calmodulin-dependent protein kinase cascade in glucose upregulation of insulin gene expression.2004
Author(s)
Yu X, Murao K, Sayo Y, Imachi H, Cao WM, Ohtsuka S, Niimi M, Tokumitsu H, Inuzuka H, Wong NC, Kobayashi R, Ishida T.
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Journal Title
Diabetes. 53
Pages: 1475-1481
Description
「研究成果報告書概要(欧文)」より
Related Report
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