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

Masatoshi Nomura, Hidetaka Morinaga, Hai Lei Zhu, Lixiang Wang, Nao Hasuzawa, Ryoichi Takayanagi, Noriyoshi Teramoto

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)440-446
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume450
Issue number1
DOIs
Publication statusPublished - Jul 18 2014

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Activin Receptors
Activins
Adenosine Triphosphate
Chemical activation
Insulin
KATP Channels
Glucose
Modulation
Clamping devices
Patch-Clamp Techniques
Transgenic Mice
Genes
Defects

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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. / Nomura, Masatoshi; Morinaga, Hidetaka; Zhu, Hai Lei; Wang, Lixiang; Hasuzawa, Nao; Takayanagi, Ryoichi; Teramoto, Noriyoshi.

In: Biochemical and Biophysical Research Communications, Vol. 450, No. 1, 18.07.2014, p. 440-446.

Research output: Contribution to journalArticle

Nomura, Masatoshi ; Morinaga, Hidetaka ; Zhu, Hai Lei ; Wang, Lixiang ; Hasuzawa, Nao ; Takayanagi, Ryoichi ; Teramoto, Noriyoshi. / 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. In: Biochemical and Biophysical Research Communications. 2014 ; Vol. 450, No. 1. pp. 440-446.
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