@article{oai:soar-ir.repo.nii.ac.jp:00003748,
 author = {Ishii,  Hiroaki and Sato,  Yoshihiko and Takei,  Masahiro and Nishio,  Shinichi and Komatsu,  Mitsuhisa},
 issue = {7},
 journal = {ENDOCRINE JOURNAL},
 month = {Jan},
 note = {Pancreatic beta cell dysfunction is pivotal to the development of diabetes, and restoration of insulin action is of primary importance. Here, we present a review of the mechanism of insulin secretion by pancreatic beta cells and discuss the mutual interaction of signaling pathways in stimulus-secretion coupling to better understand the scientific basis of pharmacological treatment for insulin secretion deficiency. Glucose stimulates insulin secretion via membrane depolarization by closure of ATP-sensitive K(+) channels (K(ATP) channels) and opening of L-type voltage-dependent Ca(2+) channels. The resultant elevation of cytosolic free Ca2+ triggers insulin exocytosis. This is termed the "K(ATP)-dependent pathway" and is shared by sulfonylurea, which closes K(ATP) channels. Glucose also stimulates insulin release independent of its action on K(ATP) channels. This is referred to as the "K(ATP)-independent pathway," the molecular basis of which remains elusive. In the pancreatic beta cell, incretin hormones increase cAMP level, which enhances glucose-stimulated insulin release by protein kinase A-dependent and -independent mechanisms. Importantly, cAMP does not directly augment Ca(2+)-stimulated insulin release per se. The stimulatory level of ambient glucose is an absolute requirement for incretin to enhance insulin release. Therefore, incretin/cAMP enhances K(ATP)-independent insulinotropic action of glucose. The robust glucose-lowering effect of DPP4 inhibitor add-on in diabetic patients with sulfonylurea secondary failure is intriguing. With the clinical availability of DPP4 inhibitor and GLP-1 mimetics, the importance of the interactions between cAMP signaling and K(ATP) channel-independent actions of glucose is reappraised., Article, ENDOCRINE JOURNAL. 58(7):519-525 (2011)},
 pages = {519--525},
 title = {Glucose-incretin interaction revisited},
 volume = {58},
 year = {2011}
}