| Project/Area Number |
13671151
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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 |
Endocrinology
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| Research Institution | Shinshu University |
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Principal Investigator |
KOMATSU Mitsuhisa Shinshu University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 講師 (90221978)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAUCHI Keishi Shinshu University, Shinshu University Hospital, Associate Professor, 医学部附属病院, 講師 (30191191)
AIZAWA Toru Shinshu University, Center for Health, Safety and Environmental Management, Professor, 健康安全センター, 教授 (90150896)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | insulin release / secretion / acylation / cAMP / Ca2+ / type 2 diabetes / アシル化 / 膵β細胞 / 膵ベータ細胞 / 細胞内Ca^<2+>濃度 |
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| Research Abstract |
Insulin release from pancreatic β-cell is regulated by multiple distinct mechanisms, which are mutually related. Among various insulin secretagogues, glucose is the most powerful and important one. Glucose is known to stimulate insulin release via KATP channel-dependent and -independent mechanisms. Molecular basis for the KATP channel-dependent mechanism has relatively well established. Our research purpose is, therefore, to elucidate the mechanisms of KATP channel-independent pathways. Before this research was started, we and others had obtained considerable amount of evidence that support an involvement of glucose-induced changes in lipid signaling cascades in the KATP channel-independent ones. In particular, protein acylation was implicated as an underlying molecular event in nutrient-induced insulin secretion. In this research period, we have extensively challenged to identify the β-cell proteins that acylated by nutrient such as glucose. Finally, we identified rapidly turning over
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palmitoylated (one form of acylation) 24-kDa proteins from isolated rat pancreatic islets (Endocrinology 144 : 5232-5241, 2003). Knowing that the 24 kDa proteins are targets for nutrient stimuli in the β-cell, we are now trying to reveal nature of the proteins and to study functional roles of the proteins in controlling insulin release under various conditions. Another aspect of the fruits in this research period is that we successfully demonstrate previously unknown effect of CAMP in stimulus-secretion coupling in the β-cell. We found that (1) : cAMP increased readily releasable pool of insulin granules irrespective of the presence or absence of Ca2+, and it induced Ca2+-independent, time-dependent potentiation of subsequent insulin release (Endocrinology 143 : 4203-4209, 2002), (2) ; given cellular cAMP is increased, glucose does trigger insulin release under the condition where glucose is not capable to elevate cytosolic free Ca2+ concentration (Diabetes 51 : S29-S32, 2002). These findings improved our understandings of mechanisms of insulin release. In future, we will approach to mechanisms of impaired insulin secretion in patients with type 2 diabetes by extending our knowledge of the mechanisms of insulin secretion Less
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