1999 Fiscal Year Final Research Report Summary
Characterizetion of glucose-induced signal transduction and its impairment in type 2 diabete
| Project/Area Number |
09470219
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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 |
内分泌・代謝学
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| Research Institution | Kyoto University |
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Principal Investigator |
SEINO Yutaka Dept of Metab. And Clin. Nutr. Kyoto Univ. School of Med, Professor, 医学研究科, 教授 (40030986)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Yuichiro Dept. of Metab. And Clin. Nutr. Kyoto Univ. School of Med., Associate professor, 医学研究科, 助教授 (60283610)
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| Project Period (FY) |
1997 – 1999
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| Keywords | CREM / cAMP / PKA / GIP / insulin gene / glucose-responsive / CaMK TV / ATF2 |
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| Research Abstract |
In pancreatic β-cells, elevated glucose concentration induces not only insulin secretion but also insulin biosynthesis. Intracellular signal mediators including cAMP and calcium ion might act on cAMP responsive elements (CREs) of insulin gene through activation of protein kinase A (PKA) and calmodulin kinase IV (CaMKIV) and increase the expression of insulin gene. In this study, we examined the effects of ATF2 (CRE-BP1) and CREM, both of which belong to the CREB/ATF family and are expressed in pancreatic β-cells. When ATF2 was expressed in isolated rat pancreatic islets, glucose-induced insulin gene expression was augmented, while CREB repressed it. The transactivation domain of ATF2 was activated by CaMKIV but not by PKA. Three residues of threonine were important for the activation by CaMKIV. There are several isorforms of CREM. We found four novel isoforms expressed in pancreatic islets. P and Q domains of CREM were important for glucose-induced insulin expression, interacting with TATA-binding protein and TAF130. These studies demonstrate that transcriptional regulation via CRE is important for glucose-induced insulin gene expression.
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