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肌醇六磷酸通过激活蛋白激酶C刺激胰岛素的非Ca2+介导分泌并引发Ca2+介导的胰岛素胞吐作用。

Inositol hexakisphosphate stimulates non-Ca2+-mediated and primes Ca2+-mediated exocytosis of insulin by activation of protein kinase C.

作者信息

Efanov A M, Zaitsev S V, Berggren P O

机构信息

The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute, Karolinska Hospital, S-17176 Stockholm, Sweden.

出版信息

Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4435-9. doi: 10.1073/pnas.94.9.4435.

Abstract

D-myo-inositol 1,2,3,4,5,6-hexakisphosphate (InsP6), formed via complex pathways of inositol phosphate metabolism, composes the main bulk of inositol polyphosphates in the cell. Relatively little is known regarding possible biological functions for InsP6. We now show that InsP6 can modulate insulin exocytosis in permeabilized insulin-secreting cells. Concentrations of InsP6 above 20 microM stimulated insulin secretion at basal Ca2+-concentration (30 nM) and primed Ca2+-induced exocytosis (10 microM), both effects being due to activation of protein kinase C. Our results suggest that InsP6 can play an important modulatory role in the regulation of processes such as exocytosis in insulin-secreting cells. The specific role for InsP6 can then be to recruit secretory granules to the site of exocytosis.

摘要

D-肌醇1,2,3,4,5,6-六磷酸(InsP6)通过肌醇磷酸代谢的复杂途径形成,构成细胞中肌醇多磷酸的主要部分。关于InsP6可能的生物学功能,人们所知相对较少。我们现在表明,InsP6可以调节透化的胰岛素分泌细胞中的胰岛素胞吐作用。高于20微摩尔的InsP6浓度在基础Ca2+浓度(30纳摩尔)时刺激胰岛素分泌,并引发Ca2+诱导的胞吐作用(10微摩尔),这两种效应均归因于蛋白激酶C的激活。我们的结果表明,InsP6在调节胰岛素分泌细胞中的胞吐作用等过程中可以发挥重要的调节作用。InsP6的具体作用可能是将分泌颗粒募集到胞吐作用部位。

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