ID1-mediated bmp signaling pathway potentiates glucagon-like peptide-1 secretion in response to nutrient replenishment

Jae Woong Jeong, Minki Kim, Jiwoo Lee, Hae Kyung Lee, Younhee Ko, Hyunkyung Kim, Sungsoon Fang

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Glucagon-like peptide-1 (GLP-1) is a well-known incretin hormone secreted from enteroendocrinal L cells in response to nutrients, such as glucose and dietary fat, and controls glycemic homeostasis. However, the detailed intracellular mechanisms of how L cells control GLP-1 secretion in response to nutrients still remain unclear. Here, we report that bone morphogenetic protein (BMP) signaling pathway plays a pivotal role to control GLP-1 secretion in response to nutrient replenishment in well-established mouse enteroendocrinal L cells (GLUTag cells). Nutrient starvation dramatically reduced cellular respiration and GLP-1 secretion in GLUTag cells. Transcriptome analysis revealed that nutrient starvation remarkably reduced gene expressions involved in BMP signaling pathway, whereas nutrient replenishment rescued BMP signaling to potentiate GLP-1 secretion. Transient knockdown of inhibitor of DNA binding (ID)1, a well-known target gene of BMP signaling, remarkably reduced GLP-1 secretion. Consistently, LDN193189, an inhibitor of BMP signaling, markedly reduced GLP-1 secretion in L cells. In contrast, BMP4 treatment activated BMP signaling pathway and potentiated GLP-1 secretion in response to nutrient replenishment. Altogether, we demonstrated that BMP signaling pathway is a novel molecular mechanism to control GLP-1 secretion in response to cellular nutrient status. Selective activation of BMP signaling would be a potent therapeutic strategy to stimulate GLP-1 secretion in order to restore glycemic homeostasis.

Original languageEnglish
Article number3824
JournalInternational journal of molecular sciences
Volume21
Issue number11
DOIs
Publication statusPublished - 2020 Jun 1

Bibliographical note

Funding Information:
This study was supported by grants from the Korea Health Technology R&D Project, Ministry of Health and Welfare (HR18C0012), the National Research Foundation, Ministry of Science and ICT of Korea (NRF-2018R1A2B6003447), and faculty research grant from the Yonsei University College of Medicine (6-2017-0099) to S.F.; and the National Research Foundation, Ministry of Science and ICT of Korea (NRF-2020R1C1C1010489), and Korea University Medical Center Grant (K1923761) to H.K.

Funding Information:
Funding: This study was supported by grants from the Korea Health Technology R&D Project, Ministry of Health and Welfare (HR18C0012), the National Research Foundation, Ministry of Science and ICT of Korea (NRF-2018R1A2B6003447), and faculty research grant from the Yonsei University College of Medicine (6-2017-0099) to S.F.; and the National Research Foundation, Ministry of Science and ICT of Korea (NRF-2020R1C1C1010489), and Korea University Medical Center Grant (K1923761) to H.K.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Bone morphogenetic protein 4
  • Glucagon-like peptide-1
  • Incretin
  • Inhibitor of DNA binding 1
  • L cells

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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