2024-03-29T11:24:30Z
https://soar-ir.repo.nii.ac.jp/oai
oai:soar-ir.repo.nii.ac.jp:00003748
2022-12-14T04:39:38Z
461:462
Glucose-incretin interaction revisited
Ishii, Hiroaki
Sato, Yoshihiko
Takei, Masahiro
Nishio, Shinichi
Komatsu, Mitsuhisa
Glucose
Insulin secretion
ATP-sensitive K(+) channel
Incretin
cAMP
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)
journal article
JAPAN ENDOCRINE SOC
2011-01-07
application/pdf
ENDOCRINE JOURNAL
7
58
519
525
0918-8959
AA10901436
https://soar-ir.repo.nii.ac.jp/record/3748/files/Glucose-incretin_interaction_revisited.pdf
eng
21701075
https://pubmed.ncbi.nlm.nih.gov/21701075
10.1507/endocrj.EJ11-0064
https://doi.org/10.1507/endocrj.EJ11-0064
Copyright© The Japan Endocrine Society