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  1. AU="Isaac S. Lee"
  2. AU="Bals, Julia"
  3. AU="Rovira-Clavé, Xavier"
  4. AU="Den Boer, Monique L"
  5. AU="Potts, T."
  6. AU="Cifuentes-Diaz, Carmen"
  7. AU="Alvim, Ricardo G"
  8. AU="Barron II, Joseph C"
  9. AU="Godin, Shea-Lee"
  10. AU="Leng, Chengcai"
  11. AU="Hyslop, Brian W"
  12. AU="Suzanne Fischer"
  13. AU="Aboelata, Noha"
  14. AU="Chiang, Sarah N"
  15. AU="Wessel, Kristin M"
  16. AU="Wilson, Jenna M"
  17. AU="Goines, Paula"
  18. AU=Ippolito Mariachiara AU=Ippolito Mariachiara
  19. AU="Jose Chauca"
  20. AU="Asih, Puji B S"
  21. AU="Dsane-Selby, Lydia"
  22. AU="Tolossa, Tadesse"
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Artikel ; Online: GLP-1 receptor signaling increases PCSK1 and β cell features in human α cells

Mridusmita Saikia / Marlena M. Holter / Leanne R. Donahue / Isaac S. Lee / Qiaonan C. Zheng / Journey L. Wise / Jenna E. Todero / Daryl J. Phuong / Darline Garibay / Reilly Coch / Kyle W. Sloop / Adolfo Garcia-Ocana / Charles G. Danko / Bethany P. Cummings

JCI Insight, Vol 6, Iss

2021  Band 3

Abstract: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that potentiates glucose-stimulated insulin secretion. GLP-1 is classically produced by gut L cells; however, under certain circumstances α cells can express the prohormone convertase required for ... ...

Abstract Glucagon-like peptide-1 (GLP-1) is an incretin hormone that potentiates glucose-stimulated insulin secretion. GLP-1 is classically produced by gut L cells; however, under certain circumstances α cells can express the prohormone convertase required for proglucagon processing to GLP-1, prohormone convertase 1/3 (PC1/3), and can produce GLP-1. However, the mechanisms through which this occurs are poorly defined. Understanding the mechanisms by which α cell PC1/3 expression can be activated may reveal new targets for diabetes treatment. Here, we demonstrate that the GLP-1 receptor (GLP-1R) agonist, liraglutide, increased α cell GLP-1 expression in a β cell GLP-1R–dependent manner. We demonstrate that this effect of liraglutide was translationally relevant in human islets through application of a new scRNA-seq technology, DART-Seq. We found that the effect of liraglutide to increase α cell PC1/3 mRNA expression occurred in a subcluster of α cells and was associated with increased expression of other β cell–like genes, which we confirmed by IHC. Finally, we found that the effect of liraglutide to increase bihormonal insulin+ glucagon+ cells was mediated by the β cell GLP-1R in mice. Together, our data validate a high-sensitivity method for scRNA-seq in human islets and identify a potentially novel GLP-1–mediated pathway regulating human α cell function.
Schlagwörter Endocrinology ; Metabolism ; Medicine ; R
Thema/Rubrik (Code) 571
Sprache Englisch
Erscheinungsdatum 2021-02-01T00:00:00Z
Verlag American Society for Clinical investigation
Dokumenttyp Artikel ; Online
Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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