Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Recently published
    • Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Recently published
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
GLP-1 receptor signaling increases PCSK1 and β cell features in human α cells
Mridusmita Saikia, … , Charles G. Danko, Bethany P. Cummings
Mridusmita Saikia, … , Charles G. Danko, Bethany P. Cummings
Published February 8, 2021
Citation Information: JCI Insight. 2021;6(3):e141851. https://doi.org/10.1172/jci.insight.141851.
View: Text | PDF
Research Article Endocrinology Metabolism

GLP-1 receptor signaling increases PCSK1 and β cell features in human α cells

  • Text
  • PDF
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.

Authors

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

×

Graphical abstract

Options: View larger image (or click on image)
Follow JCI Insight:
Copyright © 2021 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts