2006 Fiscal Year Final Research Report Summary
Development of Metal Complexes with Antidialetic Effect
| 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)
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| Project Period (FY) |
2004 – 2006
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| Keywords | diabetes mellitus / metabolic syndrome / vanadium complex / zinc complex / insulin-mimetic action / hypoglycemic effect / drug delivery system |
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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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[Journal Article] Novel vanadyl complexes with quinoxaline N^1,N^4-dioxide derivatives as potent in vitro insulin-mimetic compounds2006
Author(s)
Pabla Noblia, Marisol Vieites, Maria H.Torre, Antonio J.Costa-Filho, Hugo Cerecetto, Mercedes Gonzalez, Maria Laura Lavaggi, Yusuke Adachi, Hiromu Sakurai, Dinorah Gambino
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Journal Title
J. Inorg. Biochem. 100(2)
Pages: 281-287
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] New vanadium(V) complexes with salicylaldehyde semicarbazone derivatives synthesis, characterization, and in vitro insulin-mimetic activity-crystal structure of [V^vO_2(salicylaldehyde semicarbazone)]2004
Author(s)
Pabla Noblia, Enrique J.Baran, Lucia Otero, Patricia Draper, Hugo Cerecetto, Mercedes Gonzalez, Oscar E.Piro, Eduardo E.Castellano, Toshifumi Inohara, Yusuke Adachi, Hiromu Sakurai, Dinorah Gambino
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Journal Title
Eur. J. Inorg. Chem. 2004(2)
Pages: 322-328
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Synthesis and insulinomimetic activities of novel mono- and tetranuclear oxovanadium(IV) complexes with 3-hydroxypyridine-2- carboxylic acid2004
Author(s)
Misaki Nakai, Makoto Obata, Fumi Sekiguchi, Masako Kato, Motoo Shiro, Akio Ichimura, Isamu Kinoshita, Masahiro Mikuriya, Toshifumi Inohara, Kenji Kawabe, Hiromu Sakurai, Chris Orvig, Shigenobu Yano
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Journal Title
J. Inorg. Biochem. 98(1)
Pages: 105-112
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Vanadium2004
Author(s)
Hiromu Sakurai
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Journal Title
Comprehensive Manual for Biochemical and Immunological Aspects of Clinical Pathology (2) 6th Edition, Nippon Rinsho 62(12)
Pages: 322-325
Description
「研究成果報告書概要(欧文)」より
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[Book] 生命元素事典2006
Author(s)
腰井 弘
Total Pages
440
Publisher
オーム社
Description
「研究成果報告書概要(和文)」より
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