CREB/CRTC2 controls GLP-1-dependent regulation of glucose homeostasis
DC Field | Value | Language |
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dc.contributor.author | Lee, Ji-Hyun | - |
dc.contributor.author | Wen, Xianlan | - |
dc.contributor.author | Cho, Hana | - |
dc.contributor.author | Koo, Seung-Hoi | - |
dc.date.accessioned | 2021-09-02T14:48:26Z | - |
dc.date.available | 2021-09-02T14:48:26Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2018-03 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/77280 | - |
dc.description.abstract | Glucagon-like peptide 1 (GLP-1) is a major incretin that controls glucose homeostasis. The secretion of mature GLP-1 is regulated via GPCRs, including bile acid receptor G protein-coupled bile acid receptor 1, which uses cAMP signaling to enhance the exocytosis of GLP-1-containing vesicles. However, the role of cAMP-mediated transcription has not been clearly demonstrated to date. In this study, we explored the role of cAMP response element-binding protein/CREB-regulated transcription coactivator 2 (CREB/CRTC2)-dependent transcription on GLP-1 secretion in the L cells. We found that the reduced CREB/CRTC2 activity impaired the cAMP-dependent increase in GLP-1 secretion, whereas expression of constitutively active CRTC2 increased GLP-1 exocytosis from the L cells. Close investigation revealed that expression of not only proglucagon but also PC1/3, an endopeptidase for GLP-1 maturation, is transcriptionally regulated by CREB/CRTC2. Furthermore, expression of peroxisome proliferator-activating receptor coactivator 1 a is also reduced upon depletion of CRTC2, leading to the decreased expression of oxidative phosphorylation (OxPhos) genes, reduced ATP levels, and calcium concentrations in the L cells. Finally, we observed that intestine-specific CRTC2 knockout mice displayed reduced GLP-1 expression, leading to the lower plasma GLP-1 levels, impaired glucose tolerance, and decreased insulin-containing beta cells in pancreatic islets. Our data show that the CREB/CRTC2-dependent transcriptional pathway is critical for regulating glucose homeostasis by controlling production of GLP-1 from the L cells at the level of transcription, maturation, and exocytosis. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | FEDERATION AMER SOC EXP BIOL | - |
dc.subject | GLUCAGON-LIKE PEPTIDE-1 | - |
dc.subject | PROGLUCAGON GENE-EXPRESSION | - |
dc.subject | CREB COACTIVATOR TORC2 | - |
dc.subject | INSULIN-SECRETION | - |
dc.subject | INCRETIN HORMONES | - |
dc.subject | KEY REGULATOR | - |
dc.subject | PREPROGLUCAGON | - |
dc.subject | PANCREAS | - |
dc.subject | PROTEIN | - |
dc.subject | CELLS | - |
dc.title | CREB/CRTC2 controls GLP-1-dependent regulation of glucose homeostasis | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Koo, Seung-Hoi | - |
dc.identifier.doi | 10.1096/fj.201700845R | - |
dc.identifier.scopusid | 2-s2.0-85043584813 | - |
dc.identifier.wosid | 000427246000035 | - |
dc.identifier.bibliographicCitation | FASEB JOURNAL, v.32, no.3, pp.1566 - 1578 | - |
dc.relation.isPartOf | FASEB JOURNAL | - |
dc.citation.title | FASEB JOURNAL | - |
dc.citation.volume | 32 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 1566 | - |
dc.citation.endPage | 1578 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Life Sciences & Biomedicine - Other Topics | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | GLUCAGON-LIKE PEPTIDE-1 | - |
dc.subject.keywordPlus | PROGLUCAGON GENE-EXPRESSION | - |
dc.subject.keywordPlus | CREB COACTIVATOR TORC2 | - |
dc.subject.keywordPlus | INSULIN-SECRETION | - |
dc.subject.keywordPlus | INCRETIN HORMONES | - |
dc.subject.keywordPlus | KEY REGULATOR | - |
dc.subject.keywordPlus | PREPROGLUCAGON | - |
dc.subject.keywordPlus | PANCREAS | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordAuthor | cAMP signaling | - |
dc.subject.keywordAuthor | transcriptional activator | - |
dc.subject.keywordAuthor | glucose metabolism | - |
dc.subject.keywordAuthor | intestinal L cells | - |
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