Intra-islet α-cell Gs signaling promotes glucagon release

Liu Liu (), Kimberley El, Diptadip Dattaroy, Luiz F. Barella, Yinghong Cui, Sarah M. Gray, Carla Guedikian, Min Chen, Lee S. Weinstein, Emily Knuth, Erli Jin, Matthew J. Merrins, Jeffrey Roman, Klaus H. Kaestner, Nicolai Doliba, Jonathan E. Campbell and Jürgen Wess ()
Additional contact information
Liu Liu: National Institute of Diabetes and Digestive and Kidney Diseases
Kimberley El: Duke University
Diptadip Dattaroy: National Institute of Diabetes and Digestive and Kidney Diseases
Luiz F. Barella: National Institute of Diabetes and Digestive and Kidney Diseases
Yinghong Cui: National Institute of Diabetes and Digestive and Kidney Diseases
Sarah M. Gray: Duke University
Carla Guedikian: Duke University
Min Chen: National Institute of Diabetes and Digestive and Kidney Diseases
Lee S. Weinstein: National Institute of Diabetes and Digestive and Kidney Diseases
Emily Knuth: University of Wisconsin-Madison
Erli Jin: University of Wisconsin-Madison
Matthew J. Merrins: University of Wisconsin-Madison
Jeffrey Roman: University of Pennsylvania
Klaus H. Kaestner: University of Pennsylvania
Nicolai Doliba: University of Pennsylvania
Jonathan E. Campbell: Duke University
Jürgen Wess: National Institute of Diabetes and Digestive and Kidney Diseases

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Glucagon, a hormone released from pancreatic α-cells, is critical for maintaining euglycemia and plays a key role in the pathophysiology of diabetes. To stimulate the development of new classes of therapeutic agents targeting glucagon release, key α-cell signaling pathways that regulate glucagon secretion need to be identified. Here, we focused on the potential importance of α-cell Gs signaling on modulating α-cell function. Studies with α-cell-specific mouse models showed that activation of α-cell Gs signaling causes a marked increase in glucagon secretion. We also found that intra-islet adenosine plays an unexpected autocrine/paracrine role in promoting glucagon release via activation of α−cell Gs-coupled A2A adenosine receptors. Studies with α-cell-specific Gαs knockout mice showed that α-cell Gs also plays an essential role in stimulating the activity of the Gcg gene, thus ensuring proper islet glucagon content. Our data suggest that α-cell enriched Gs-coupled receptors represent potential targets for modulating α-cell function for therapeutic purposes.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-49537-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49537-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-49537-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().