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 β-cells

Endocrine Journal

Shin-ichi Nishio²  Katsuya Dezaki¹  Yoshihiko Sato²  Toshihiko Yada¹  Satoru Suzuki²  Mitsuhisa Komatsu²  Hiroaki Ishii²  Masahiro Takei² 

[1] Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan;Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Shinshu University School of Medicine, Matsumoto 390-8621, Japan

关键词: Glucose;    Cyclic AMP;    KATP channel;    Insulin release;   

DOI  :  10.1507/endocrj.EJ12-0388

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(32)Cited-By(5)In pancreatic β-cells, glucose metabolism leads to closure of ATP sensitive K+ channels (KATP 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 KATP 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 β-cells.Glucose-induced insulin release was abolished when Ca2+ influx was inhibited by a combination of 250 μM diazoxide, an opener of KATP channel, and 10 μM 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 μM 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 α-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.

【 授权许可】

Unknown