| Project/Area Number |
16001003
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
Chemistry
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
SAKURAI Hiromu Kyoto Pharmaceutical University, Pharmacology, Professor, 薬学部, 教授 (30065916)
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| Co-Investigator(Kenkyū-buntansha) |
YASUI Hiroyuki Kyoto Pharmaceutical University, Pharmacology, Assistant Professor, 薬学部, 助教授 (20278443)
YOSHIKAWA Yutaka Kyoto Pharmaceutical University, Pharmacology, Research Assistant, 薬学部, 助手 (20388028)
HIROMURA Makoto Kyoto Pharmaceutical University, Pharmacology, Post Doctor, 薬学部, PD (30411036)
小嶋 良種 大阪市立大学, 大学院・理学研究科, 特任教授 (40047139)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥135,330,000 (Direct Cost: ¥104,100,000、Indirect Cost: ¥31,230,000)
Fiscal Year 2006: ¥36,660,000 (Direct Cost: ¥28,200,000、Indirect Cost: ¥8,460,000)
Fiscal Year 2005: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2004: ¥72,670,000 (Direct Cost: ¥55,900,000、Indirect Cost: ¥16,770,000)
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| Keywords | diabetes mellitus / metabolic syndrome / vanadium complex / zinc complex / insulin-mimetic action / hypoglycemic effect / drug delivery system / 糖尿病治療 / ドラッグデリバリー系 / ポルフィリン錯体 / 糖尿病治療薬 / インスリン注射 / 金属錯体 / バナジウム / 亜鉛 / アリキシン / インスリンシグナル伝達経路 |
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| Research Abstract |
Diabetes mellitus (DM) with a common pathogenesis of hyperglycemia is classified into two types; insulin-dependent type 1 DM characterized by the absence of insulin synthesis and secretion in the pancreas, and non-insulin-dependent type 2 DM characterized by insulin resistance due to obesity.
The former is treated only by daily insulin injections and the latter needs exercise and diet control along with the administration of oral synthetic medicines. Daily insulin injections are associated with physical and spiritual burden, and, in addition, the long-term insulin injections leads to the formation of self-antibodies in some patients. The administration of oral medicines causes the pancreas to discontinue insulin synthesis because of a reduced insulin demand. This in turn necessitates the need for insulin injections. In order to overcome the defects of insulin injections and oral medicines, we have planed to develop new antidiabetic agents with a novel mechanism of action. For this purpose, we used metal complexes to treat both types of DM in experimental animals. On the basis of the results, we found the followng facts. (1) A new in vitro evaluation system was established in terms of glucose uptake and inhibition of free fatty acid release in the adipocytes, (2) In vanadyl (+4)-picolinate complexes, the importance of the substituent position rather than the electronic effect was conclude to enhance the hypoglycemic activity of the complexes. (3) In the study on structure-activity relationship for vanadyl- and zinc-3-hydroxypyrone complexes, excellent allixin-related complexes, which improve not only antidiabetic state but also anti-metabolic syndromes, were found, (4) The complexes have been revealed to act on the insulin signaling cascade, and finally to transport the glucose transporter 4 in the cell membranes, and (5) Some drug delivery systems were proposed for vanadyl compounds. From these facts, several complexes for clinical trials in the future were proposed.
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