Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity.
Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity.
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DOI：
10.1038/srep06689
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发表时间：
2014-10-21
影响因子：
4.6
通讯作者：
Moriyama Y
中科院分区：
文献类型：
--
作者：
Sakamoto S;Miyaji T;Hiasa M;Ichikawa R;Uematsu A;Iwatsuki K;Shibata A;Uneyama H;Takayanagi R;Yamamoto A;Omote H;Nomura M;Moriyama Y
神经内分泌细胞将ATP储存在分泌颗粒中，并将其沿着激素释放，这些激素可能在称为嘌呤能化学传递的过程中引发各种细胞反应。虽然囊泡核苷酸转运蛋白（VNUT）已被证明参与囊泡储存和ATP的释放，但其在体内的生理相关性远未得到很好的理解。在Vnut基因敲除（Vnut−/−）小鼠中，我们发现肾上腺嗜铬颗粒和胰岛中胰岛素颗粒的功能性VNUT丧失导致了几种显著的影响。Vnut−/−小鼠的嗜铬颗粒中不存在囊泡ATP蓄积和去极化依赖性ATP释放。在Vnut−/−小鼠的胰腺β细胞中也不存在葡萄糖响应性ATP释放，而葡萄糖响应性胰岛素分泌比野生型组织中更大程度地增强。由于胰岛素敏感性增加，Vnut−/−小鼠在禁食时表现出改善的葡萄糖耐量和低血糖。这些结果表明VNUT在体内神经内分泌细胞囊泡储存和释放ATP中的重要作用，并表明囊泡ATP和/或其降解产物在儿茶酚胺和胰岛素分泌中充当反馈调节剂，从而调节血糖稳态。
Neuroendocrine cells store ATP in secretory granules and release it along with hormones that may trigger a variety of cellular responses in a process called purinergic chemical transmission. Although the vesicular nucleotide transporter (VNUT) has been shown to be involved in vesicular storage and release of ATP, its physiological relevance in vivo is far less well understood. In Vnut knockout (Vnut−/−) mice, we found that the loss of functional VNUT in adrenal chromaffin granules and insulin granules in the islets of Langerhans led to several significant effects. Vesicular ATP accumulation and depolarization-dependent ATP release were absent in the chromaffin granules of Vnut−/− mice. Glucose-responsive ATP release was also absent in pancreatic β-cells in Vnut−/− mice, while glucose-responsive insulin secretion was enhanced to a greater extent than that in wild-type tissue. Vnut−/− mice exhibited improved glucose tolerance and low blood glucose upon fasting due to increased insulin sensitivity. These results demonstrated an essential role of VNUT in vesicular storage and release of ATP in neuroendocrine cells in vivo and suggest that vesicular ATP and/or its degradation products act as feedback regulators in catecholamine and insulin secretion, thereby regulating blood glucose homeostasis.
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影响因子：
7.3
作者：
HILLAIREBUYS, D;BERTRAND, G;LOUBATIERESMARIANI, MM
通讯作者：
LOUBATIERESMARIANI, MM
DOI：
10.1016/j.ijdevneu.2005.07.004
发表时间：
2005-11-01
影响因子：
1.8
作者：
Afework, M;Burnstock, G
通讯作者：
Burnstock, G
影响因子：
8.2
作者：
Amisten, S.;Meidute-Abaraviciene, S.;Erlinge, D.
通讯作者：
Erlinge, D.
影响因子：
7.7
作者：
Enjyoji, Keiichi;Kotani, Ko;Thukral, Chandrashekar;Blumel, Benjamin;Sun, Xiaofeng;Wu, Yan;Imai, Masato;Friedman, David;Csizmadia, Eva;Bleibel, Wissam;Kahn, Barbara B.;Robson, Simon C.
通讯作者：
Robson, Simon C.
影响因子：
7.7
作者：
LACY, PE;KOSTIANOVSKY, M
通讯作者：
KOSTIANOVSKY, M