1997 Fiscal Year Final Research Report Summary
Studies on orally active antidiabetic vanadium complexes with low toxicity and long-term action
| Project/Area Number |
08457622
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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 |
医薬分子機能学
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
SAKURAI Hiromu Kyoto Pharm.Univ., Dep.Anal.& Bioinorg.Chem., Prof., 薬学部, 教授 (30065916)
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| Co-Investigator(Kenkyū-buntansha) |
OKA Shigenori Kyoto Pharm.Univ., Dep.Anal.& Bioinorg.Chem., Res.Assist., 薬学部, 助手 (10268097)
YASUI Hiroyuki Kyoto Pharm.Univ., Dep.Anal.& Bioinorg.Chem., Res.Assist., 薬学部, 助手 (20278443)
TAWA Riich Kyoto Pharm.Univ., Dep.Anal.& Bioinorg.Chem., Lec., 薬学部, 講師 (80142587)
KANAMORI Kan Toyama Univ., Fac.Sci., Prof., 理学部, 教授 (00019001)
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| Project Period (FY) |
1996 – 1997
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| Keywords | vanadium / vanadyl complex / diabetes / insulin-like action / nitric oxide / IDDM / NIDDM |
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| Research Abstract |
We studied on development of orally active antidiabetic vanadyl complexes with low toxicity and long-term action to know the structure of the complex-activity relationship. Research was performed in the following steps. (1) Preparation of vanadyl complexes with different coordination modes and analysis of the structure. (2) In vitro evaluation of the complex using rat adipocytes in terms of suppression of free fatty acids and (3) in vivo evaluation of the possible complex, which was given to streptozotocin (STZ)-induced insulin-dependent diabetes mellitus (IDDM) rats or none-insulin-dependent diabetes mellitus (NIDDM) mice by ip injection or oral administration.
From the results for 2 years, we found that a vanadyl-picolinate complex with vo (v_2o_2) coordination mode has a good blood glucose normalizing effect on oral administration. Then we extended our work to find better complexes and found vanadyl-6-methyl-picolinate complex with low toxicity and long-term action when administered orally. The action mechanism of the complex was also analyzed in terms of vanadium organ distribution and pharmacokinetics. Interestingly, the complex was found to be effective on NIDDM mice when given by ip injection or oral administration. On the other hand, vanadium was found to be effective on the protection of development of STZ-induced diabetes. On the basis of the results, vanadium compounds were found to be effective to treat both IDDM and NIDDM in experimental animals as well as to protect the development of IDDM.
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