5.組織化学面より見たラ氏島分泌異常の種々相
スポンサーリンク
概要
- 論文の詳細を見る
In this experiment the mechanism involved in the phenomenon of hypoglycemia induced by the administration of sulfonylurea, and by the administration of leucine in leucine sensitive cases was studied by using sulfonylurea, 1-leucine, and α-ketocarboxylic acids in vivo and in vitro.<BR>1. Sulfonylurea, which has a hypoglycemic effect, is coordinated to zinc ions in vitro and forms an insoluable complex. In an experiment in vivo using <SUP>35</SUP>S-Rastinon, results of autoradiography indicate the complex-formation of sulfonylurea and zinc ions in islets of pancreas. These results suggest, that the release of insulin from islets induced by the disintegration of three dimensional structured complex of zinc ions and insulin in B cells into two dimensional or lineal structured form. It is induced by the chelating of zinc ions with sulfonylurea. Namely, the block of biological activity of stainable zinc in B cells by administered sulfonylurea causes the disintegration of zinc-insulin complex and facilitates the release of insulin from islets.<BR>2. On the basis of results of morphological studies on the pancreas in 2 cases of infantile leucin sensitive hypoglycemia and on insuloma in 3 cases with the leucine sensitivity, it was concluded that, although the normal B cells of islets contain a large quantity of stainable zinc, the insulin producing cells in leucine sensitive cases contain a very small quantity of stainable zinc. And this is one and the only common finding through all cases. It is speculated, that in leucine sensitive cases these small quantities of zinc ions combine with S atoms of S-S bond of insulin, because these S atoms have severaly two electron lone pairs, and the coordinate bond of zinc ions and S atoms is stronger than that of zinc ions and amino acid. Therefore in leucine sensitive cases, zinc ions and insulin barely form the three dimensional structured complex. 1-leucine disintegrates easily into a-ketoisocaproic acid by existence of zinc ions. Therefore the administered leucine cannot remain intact in islets; and a-ketoisocaproic acid (a metobolite of leucine) or its metabolite, reacts in islets. Although the essential amino acids (except leucine) cannot decompose the three dimensional structured complex of zinc-insulin, α-ketoisocaproic acid can decompose the complex. Results of an experiment in vitro support the above mentioned speculation. Namely, the white precipitate, which was deposited by adding an aqueous solution containing zinc chloride into the standard insulin solution, was dissolved by adding an aqueous solution of α-ketoisocaproic acid. Results of an optical rotatory examination in this experiment system also support this specutaion. The same fact occurred in an experiment of α-ketobutyric acid system.<BR>3. Based on this speculation on the mechanism of leucine sensitivity, the hypoglycemic effect of α-ketobutyric acid was studied in leucine sensitive cases. α-ketobutyric acid shows a hypoglycemic effect in cases with leucine sensitivity of human and rat, and this effect is caused by the stimulation of insulin-release from islet induced by the administration of this substance.<BR>From results of these experiments, it is concluded that the release of insulin from islets is strongly influenced by the stainable zinc in B cells. These zinc ions form the three dimensional structured complex with insulin, and the decomposure of this complex induced by the chelating of zinc ions facilitates the release of insulin from islets.<BR>For revealing leucine sensitivity, it may be a very important factor that the quantity of stainable zinc in insulin producing cells is very small, and based upon this factor the mechanism of sensitivity to leucine was discussed.
- 日本内分泌学会の論文