title: Activation of activin type IB receptor signals in pancreatic β cells leads to defective insulin secretion through the attenuation of ATP-sensitive K+ channel activity.
abstract: In studies of gene-ablated mice, activin signaling through activin type IIB receptors (ActRIIB) and Smad2 has been shown to regulate not only pancreatic β cell mass but also insulin secretion. However, it still remains unclear whether gain of function of activin signaling is involved in the modulation of pancreatic β cell mass and insulin secretion. To identify distinct roles of activin signaling in pancreatic β cells, the Cre-loxP system was used to activate signaling through activin type IB receptor (ActRIB) in pancreatic β cells. The resultant mice (pancreatic β cell-specific ActRIB transgenic (Tg) mice; ActRIBCAβTg) exhibited a defect in glucose-stimulated insulin secretion (GSIS) and a progressive impairment of glucose tolerance. Patch-clamp techniques revealed that the activity of ATP-sensitive K(+) channels (KATP channels) was decreased in mutant β cells. These results indicate that an appropriate level of activin signaling may be required for GSIS in pancreatic β cells, and that activin signaling involves modulation of KATP channel activity.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi Ward, Fukuoka 812-8582, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nomura
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi Ward, Fukuoka 812-8582, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Morinaga
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Saga 849-8501, Japan.
authors.forename: Hai-Lei
authors.initials: HL
authors.lastname: Zhu
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi Ward, Fukuoka 812-8582, Japan.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi Ward, Fukuoka 812-8582, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Hasuzawa
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi Ward, Fukuoka 812-8582, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Saga 849-8501, Japan; Laboratory of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba Ward, Sendai 980-8575, Japan. Electronic address: noritera@cc.saga-u.ac.jp.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Teramoto
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism*; D028341:Activins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology; D054086:KATP Channels / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007328:Insulin; D054086:KATP Channels; D028341:Activins; D030201:Activin Receptors, Type I; D005947:Glucose
keywords: Activin receptor; Insulin secretion; K(ATP) channels; Pancreas; Transgenic mouse; β cells