Item type |
学術雑誌論文 / Journal Article(1) |
公開日 |
2014-06-27 |
タイトル |
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タイトル |
A new experimental model of ATP-sensitive K+ channel-independent insulinotropic action of glucose: a permissive role of cAMP for triggering of insulin release from rat pancreatic beta-cells |
言語 |
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言語 |
eng |
DOI |
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関連識別子 |
https://doi.org/10.1507/endocrj.EJ12-0388 |
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関連名称 |
10.1507/endocrj.EJ12-0388 |
資源タイプ |
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資源 |
http://purl.org/coar/resource_type/c_6501 |
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タイプ |
journal article |
著者 |
Takei, Masahiro
Dezaki, Katsuya
Ishii, Hiroaki
Nishio, Shin-ichi
Sato, Yoshihiko
Suzuki, Satoru
Yada, Toshihiko
Komatsu, Mitsuhisa
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出版者 |
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出版者 |
JAPAN ENDOCRINE SOC |
引用 |
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内容記述 |
ENDOCRINE JOURNAL. 60(5):599-607 (2013) |
書誌情報 |
ENDOCRINE JOURNAL
巻 60,
号 5,
p. 599-607,
発行日 2013-05
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内容記述 |
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内容記述 |
信州大学博士(医学)・学位論文・平成24年3月31日授与(甲第936号)・武井 真大 |
抄録 |
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内容記述 |
In pancreatic beta-cells, glucose metabolism leads to closure of ATP sensitive K+ channels (K-ATP channel) and Ca2+ influx, which is regarded as a required step for triggering of insulin release. Here, we demonstrate that glucose triggers rapid insulin release independent from its action on K-ATP channels given the cellular cAMP is elevated. We measured insulin release from rat pancreatic islets by static and perifusion experiments. Changes in cytosolic free Ca2+ concentration ([Ca2+](i)) were monitored using fura-2 loaded rat pancreatic beta-cells. Glucose-induced insulin release was abolished when Ca2+ influx was inhibited by a combination of 250 mu M diazoxide, an opener of K-ATP channel, and 10 mu M nifedipine, a blocker of L-type voltage-dependent Ca2+ channels. However, with both nifedipine and diazoxide, glucose induced a 5-fold increase in insulin release in the presence of 10 mu M forskolin, an activator of adenylyl cyclase. In the presence of diazoxide, nifedipine, and forskolin, 22 mM glucose sharply increased the rate of insulin release within 2 min which peaked at 6 min: this was followed by a further gradual increase in insulin release. In contrast, it lowered [Ca2+](i) with a nadir at 2-3 min followed by a gradual increase in [Ca2+](i). The glucose effect was mimicked by 20 mM alpha-ketoisocaproic acid, a mitochondrial fuel, and it was nullified by 2 mM sodium azide, an inhibitor of mitochondrial electron transport. Cerulenin, an inhibitor of protein acylation, decreased the glucose effect. In conclusion, a rise in [Ca2+](i) through voltage-dependent Ca2+ channels is not mandatory for glucose-induced triggering of insulin release. |
資源タイプ(コンテンツの種類) |
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内容記述 |
Article |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |