@article{oai:soar-ir.repo.nii.ac.jp:00007189,
 author = {Takei,  Masahiro and Dezaki,  Katsuya and Ishii,  Hiroaki and Nishio,  Shin-ichi and Sato,  Yoshihiko and Suzuki,  Satoru and Yada,  Toshihiko and Komatsu,  Mitsuhisa},
 issue = {5},
 journal = {ENDOCRINE JOURNAL},
 month = {May},
 note = {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, 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., Article, ENDOCRINE JOURNAL. 60(5):599-607 (2013)},
 pages = {599--607},
 title = {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},
 volume = {60},
 year = {2013}
}