α-cell glucokinase suppresses glucose-regulated glucagon secretion

Davide Basco, Quan Zhang, Albert Salehi, Andrei Tarasov, Wanda Dolci, Pedro Herrera, Ioannis Spiliotis, Xavier Berney, David Tarussio, Patrik Rorsman and Bernard Thorens ()
Additional contact information
Davide Basco: University of Lausanne
Quan Zhang: Churchill Hospital
Albert Salehi: Division of Islet Cell Physiology
Andrei Tarasov: Churchill Hospital
Wanda Dolci: University of Lausanne
Pedro Herrera: Department of Genetic Medicine and Development
Ioannis Spiliotis: Churchill Hospital
Xavier Berney: University of Lausanne
David Tarussio: University of Lausanne
Patrik Rorsman: Churchill Hospital
Bernard Thorens: University of Lausanne

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: Abstract Glucagon secretion by pancreatic α-cells is triggered by hypoglycemia and suppressed by high glucose levels; impaired suppression of glucagon secretion is a hallmark of both type 1 and type 2 diabetes. Here, we show that α-cell glucokinase (Gck) plays a role in the control of glucagon secretion. Using mice with α-cell-specific inactivation of Gck (αGckKO mice), we find that glucokinase is required for the glucose-dependent increase in intracellular ATP/ADP ratio and the closure of KATP channels in α-cells and the suppression of glucagon secretion at euglycemic and hyperglycemic levels. αGckKO mice display hyperglucagonemia in the fed state, which is associated with increased hepatic gluconeogenic gene expression and hepatic glucose output capacity. In adult mice, fed hyperglucagonemia is further increased and glucose intolerance develops. Thus, glucokinase governs an α-cell metabolic pathway that suppresses secretion at or above normoglycemic levels; abnormal suppression of glucagon secretion deregulates hepatic glucose metabolism and, over time, induces a pre-diabetic phenotype.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-03034-0 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:9:y:2018:i:1:d:10.1038_s41467-018-03034-0

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

DOI: 10.1038/s41467-018-03034-0

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 ().