The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Studies on Prevention of Experimental Diabetes Mellitus by Means of Some Chemical Substances
Kozo OKAMOTOTetsuro TAIIHiromasa KOSONorihisa TAKENAKATeisuke HAYAKAWAToshihiko IBARAKI
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1955 年 61 巻 supplIII 号 p. 36-61

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1. Eighty-six varieties of chemical substances were tested for their efficacy in preventing alloxan diabetes in white rats and 37 items among them were found effective. 33 of the tested materials were zinc-affine substances, of which. 24 were found diabeto-preventive. Of the remaining 53, which were non-zinc-affine, 14 proved to be effective in prevention.
2. Among the substances proved diabeto-preventive, we found some familiar to us in daily life and physiologically important, including 8 vitamins, mainly in B group, 6 varieties of cholic acids, theobromine, sodium bicarbonate and 7 kinds of amino acids.
3. The minimum effective doses and the duration of the effect were determined for all the preventive substances. The results showed that vitamin B12 had the strongest preventive effect, followed by benzimidazole, salicylaldoxime, sodium thiosulphate, BAL, nicotinamide, cholic acids and dopa.
4. The mechanism of diabeto-prevention was studied using 29 representative varieties of the substances found preventive, and the preventive action was found to be accomplished either intra-pancreatically, extra-pancreatically or both intra-and extra-pancreatically.
5. Of the preventive substances, the zinc-affine varieties were found to act intra-pancreatically, probably intra-insularly, without exception-a finding apparently in support of Okamoto's zinc theory of diabetes mellitus.
6. The non-zinc-affine preventive substances (substances containing SH radicals and the majority of the effective vitamins) showed mechanism of extra--pancreatic prevention in most cases. The SH radicaled substances seemingly prevent diabetes by disposing of and detoxicating alloxan before it reached the pancreas. Such considerations also led us to doubt the tenability of Lazarow's glutathione theory of diabetogenesis.
7. With 12 of the preventive reagents as material, we conducted experiments for prevention of alloxan, dithizone and 8-hydroxyquinaldine diabetes in rabbits and found that the preventive effect was considerably impaired in some of the reagents. In general, the preventive action against alloxan diabetes is weaker in rabbits than in white rats. In some cases, the result may be explained by the lower doses of preventive reagents in ratio of the augmented doses of alloxan. Dithizone diabetes was found more difficult to prevent than the diabetes induced by the two other chemicals, which fact may be interpreted as due to the stronger affinity of dithizone with zinc.
8. Eight varieties of the substances found effective in preventing diabetes in white rats were found also effective in preventing experimental diabetes induced by oxine in guinea pigs in most cases.
9. Many substances with similar chemical formula and belonging to the same family of compounds were found to differ in their action-some being diabetogenic, some diabeto-preventive and the others neither diabetogenic nor preventive. In such cases, their manner of combination with zinc, that is, the fact that they are zinc-affine or not, was found to determine their reaction in regard to diabetes.
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© Tohoku University Medical Press
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