ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment
- Authors
- Jeong, Jae Woong; Kim, Minki; Lee, Jiwoo; Lee, Hae-Kyung; Ko, Younhee; Kim, Hyunkyung; Fang, Sungsoon
- Issue Date
- 6월-2020
- Publisher
- MDPI
- Keywords
- glucagon-like peptide-1; L cells; bone morphogenetic protein 4; incretin; inhibitor of DNA binding 1
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.21, no.11
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 21
- Number
- 11
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/55551
- DOI
- 10.3390/ijms21113824
- ISSN
- 1661-6596
- 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.
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