MISC

2008年11月

Low, but Physiological, Concentration of GLP-1 Stimulates Insulin Secretion Independent of the cAMP-Dependent Protein Kinase Pathway

JOURNAL OF PHARMACOLOGICAL SCIENCES
  • Makoto Shigeto
  • ,
  • Masashi Katsura
  • ,
  • Masafumi Matsuda
  • ,
  • Seitaro Ohkuma
  • ,
  • Kohei Kaku

108
3
開始ページ
274
終了ページ
279
記述言語
英語
掲載種別
DOI
10.1254/jphs.08090FP
出版者・発行元
JAPANESE PHARMACOLOGICAL SOC

Glucagon-like peptide-1 (GLP-1) induces pancreatic insulin secretion via the cAMP-dependent protein kinase (PKA) pathway. However, the GLP-1 concentration used in the previous in vitro experiments was far from the in vivo concentrations. Alteration of plasma GLP-1 concentration at pM order lowers blood glucose concentration. In this study, we examined the GLP-1 action mechanism at a physiological concentration on insulin secretion. A high concentration of GLP-1 (10 nM) stimulated intracellular cAMP accumulation and insulin secretion was significantly inhibited by KT5720, a selective inhibitor of PKA. Low GLP-1 concentrations (1 pM) also increased insulin secretion without significant accumulation of intracellular cAMP and KT5720 did not affect insulin secretion. Insulin secretion stimulated by 1 pM GLP-1 was reduced by inhibitors of calcium action, including verapamil, dantrolene, and BAPTA. Thus, we concluded that relatively low GLP-1 concentrations-comparable to in vivo blood concentrations-promoted insulin secretion independent of the cAMP-PKA pathway. This effect was dependent on intracellular Ca(2+) concentration. The results of the present study may further the understanding of the dose-dependent response of GLP-1 signal transducing pathways and the complicated mechanism of insulin secretion. Studies of GLP-1 at physiologic concentrations may lead to new developments in studies of pancreatic beta-cell function.

リンク情報
DOI
https://doi.org/10.1254/jphs.08090FP
CiNii Articles
http://ci.nii.ac.jp/naid/10024592979
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000261353400006&DestApp=WOS_CPL
ID情報
  • DOI : 10.1254/jphs.08090FP
  • ISSN : 1347-8613
  • CiNii Articles ID : 10024592979
  • Web of Science ID : WOS:000261353400006

エクスポート
BibTeX RIS