ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment
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 n...
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doaj-955a93b16a334154aadcfef5d418225c2020-11-25T03:33:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-01213824382410.3390/ijms21113824ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient ReplenishmentJae Woong Jeong0Minki Kim1Jiwoo Lee2Hae-Kyung Lee3Younhee Ko4Hyunkyung Kim5Sungsoon Fang6Department of Medicine, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment of Medical Science, BK21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, KoreaSeverance Biomedical Science Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaSeverance Biomedical Science Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDivision of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin 17035, KoreaDepartment of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 02841, KoreaDepartment of Medical Science, BK21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, KoreaGlucagon-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.https://www.mdpi.com/1422-0067/21/11/3824glucagon-like peptide-1L cellsbone morphogenetic protein 4incretininhibitor of DNA binding 1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jae Woong Jeong Minki Kim Jiwoo Lee Hae-Kyung Lee Younhee Ko Hyunkyung Kim Sungsoon Fang |
spellingShingle |
Jae Woong Jeong Minki Kim Jiwoo Lee Hae-Kyung Lee Younhee Ko Hyunkyung Kim Sungsoon Fang ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment International Journal of Molecular Sciences glucagon-like peptide-1 L cells bone morphogenetic protein 4 incretin inhibitor of DNA binding 1 |
author_facet |
Jae Woong Jeong Minki Kim Jiwoo Lee Hae-Kyung Lee Younhee Ko Hyunkyung Kim Sungsoon Fang |
author_sort |
Jae Woong Jeong |
title |
ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment |
title_short |
ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment |
title_full |
ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment |
title_fullStr |
ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment |
title_full_unstemmed |
ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment |
title_sort |
id1-mediated bmp signaling pathway potentiates glucagon-like peptide-1 secretion in response to nutrient replenishment |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-05-01 |
description |
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. |
topic |
glucagon-like peptide-1 L cells bone morphogenetic protein 4 incretin inhibitor of DNA binding 1 |
url |
https://www.mdpi.com/1422-0067/21/11/3824 |
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