title: AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration.
abstract: 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.
authors.affiliation: Department of Endocrinology and Metabolism, Yokohama-City University, Yokohama, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Tajima
authors.forename: Jun
authors.initials: J
authors.lastname: Shirakawa
authors.forename: Yu
authors.initials: Y
authors.lastname: Togashi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Inoue
authors.forename: Koichiro
authors.initials: K
authors.lastname: Sato
authors.forename: Kazuki
authors.initials: K
authors.lastname: Orime
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Ito
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Kaji
authors.forename: Eri
authors.initials: E
authors.lastname: Sakamoto
authors.forename: Akinobu
authors.initials: A
authors.lastname: Nakamura
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Aoki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D054795:Incretins / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D054795:Incretins; D011956:Receptors, Cell Surface; D005941:Glucokinase; D000263:Adenylate Kinase; D005947:Glucose