PLoS ONE (Jan 2013)

AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration.

  • Kazuki Tajima,
  • Jun Shirakawa,
  • Yu Togashi,
  • Hideaki Inoue,
  • Koichiro Sato,
  • Kazuki Orime,
  • Yuzuru Ito,
  • Mitsuyo Kaji,
  • Eri Sakamoto,
  • Akinobu Nakamura,
  • Kazutaka Aoki,
  • Yoshio Goshima,
  • Tatsuya Atsumi,
  • Yasuo Terauchi

DOI
https://doi.org/10.1371/journal.pone.0064633
Journal volume & issue
Vol. 8, no. 5
p. e64633

Abstract

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The precise role of AMP-activated protein kinase (AMPK), a target of metformin, in pancreatic β cells remains controversial, even though metformin was recently shown to enhance the expression of incretin receptors (GLP-1 and GIP receptors) in pancreatic β cells. In this study, we investigated the effect of AMPK in the regulation of incretin receptors expression in pancreatic islets. The phosphorylation of AMPK in the mouse islets was decreased by increasing glucose concentrations. We showed the expression of incretin receptors in bell-shaped response to glucose. Expression of the incretin receptors in the isolated islets showed higher levels under a medium glucose concentration (11.1 mM) than that under a low glucose concentration (2.8 mM), but was suppressed under a high glucose concentration (22.2 mM). Both treatment with an AMPK inhibitor and DN-AMPK expression produced a significant increase of the incretin receptors expression under a low glucose concentration. By contrast, in hyperglycemic db/db islets, the enhancing effect of the AMPK inhibitor on the expression of incretin receptors was diminished under a low glucose concentration. Taken together, AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration.