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Sökning: WFRF:(Dmytriyeva Oksana) > (2018) > Enterochromaffin 5-...

  • Lund, Mari L.Section for Metabolic Receptology, Novo Nordisk Foundation Center for Basic Metabolite Research, Faculty of Health Sciences, University of Copenhagen, Denmark (författare)

Enterochromaffin 5-HT cells : A major target for GLP-1 and gut microbial metabolites

  • Artikel/kapitelEngelska2018

Förlag, utgivningsår, omfång ...

  • Elsevier,2018
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:liu-150300
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-150300URI
  • https://doi.org/10.1016/j.molmet.2018.03.004DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies|Novo Nordisk Foundation [NNF10CC1016515, NNF15CC0018346, NNF15OC0016798, NNF14OC0016798]; Danish Council for Independent Research [7016-00389A]
  • Objectives5-HT storing enterochromaffin (EC) cells are believed to respond to nutrient and gut microbial components, and 5-HT receptor-expressing afferent vagal neurons have been described to be the major sensors of nutrients in the GI-tract. However, the molecular mechanism through which EC cells sense nutrients and gut microbiota is still unclear.Methods and resultsTPH1, the 5-HT generating enzyme, and chromogranin A, an acidic protein responsible for secretory granule storage of 5-HT, were highly enriched in FACS-purified EC cells from both small intestine and colon using a 5-HT antibody-based method. Surprisingly, EC cells from the small intestine did not express GPCRsensors for lipid and protein metabolites, such as FFAR1, GPR119, GPBAR1(TGR5), CaSR, and GPR142, in contrast to the neighboring GLP-1 storing enteroendocrine cell. However, the GLP-1 receptor was particularly highly expressed and enriched in EC cells as judged both by qPCR and by immunohistochemistryusing a receptor antibody. GLP-1 receptor agonists robustly stimulated 5-HT secretion from intestinal preparations using both HPLC and a specific amperometricmethod. Colonic EC cells expressed many different types of known and potential GPCR sensors of microbial metabolites including three receptors for SCFAs, i.e. FFAR2, OLF78, and OLF558 and receptors for aromatic acids, GPR35; secondary bile acids GPBAR1; and acyl-amides and lactate, GPR132.ConclusionNutrient metabolites apparently do not stimulate EC cells of the small intestine directly but through a paracrine mechanism involving GLP-1 secreted from neighboring enteroendocrine cells. In contrast, colonic EC cells are able to sense a multitude of different metabolites generated by the gut microbiota as well as gut hormones, including GLP-1.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Egerod, Kristoffer L.Section for Metabolic Receptology, Novo Nordisk Foundation Center for Basic Metabolite Research, Faculty of Health Sciences, University of Copenhagen, Denmark (författare)
  • Engelstoft, Maja S.Section for Metabolic Receptology, Novo Nordisk Foundation Center for Basic Metabolite Research, Faculty of Health Sciences, University of Copenhagen, Denmark (författare)
  • Dmytriyeva, OksanaResearch Laboratory for Stereology and Neuroscience, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Laboratory of Neural Plasticity, Institute of Neuroscience, University of Copenhagen, Copenhagen, Denmark (författare)
  • Theodorsson, Elvar,1953-Linköpings universitet,Avdelningen för mikrobiologi och molekylär medicin,Medicinska fakulteten,Region Östergötland, Klinisk kemi(Swepub:liu)elvth65 (författare)
  • Patel, Bhavik A.School of Pharmacy and Biomolecular Sciences, University of Brighton, UK (författare)
  • Schwartz, Thue W.Section for Metabolic Receptology, Novo Nordisk Foundation Center for Basic Metabolite Research, Faculty of Health Sciences, University of Copenhagen, Denmark; Laboratory for Molecular Pharmacology, Department for Biomedical Research, Faculty of Health Sciences, University of Copenhagen, Denmark (författare)
  • Section for Metabolic Receptology, Novo Nordisk Foundation Center for Basic Metabolite Research, Faculty of Health Sciences, University of Copenhagen, DenmarkResearch Laboratory for Stereology and Neuroscience, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Laboratory of Neural Plasticity, Institute of Neuroscience, University of Copenhagen, Copenhagen, Denmark (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:MOLECULAR METABOLISM: Elsevier11, s. 70-832212-8778

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