Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production

Research output: Contribution to journalJournal article – Annual report year: 2017Researchpeer-review

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  • Author: Wewer Albrechtsen, Nicolai J.

    University of Copenhagen, Denmark

  • Author: Kuhre, Rune E.

    University of Copenhagen, Denmark

  • Author: Hornburg, Daniel

    Max Planck Institute of Biochemistry, Germany

  • Author: Jensen, Christian Z.

    University of Copenhagen, Denmark

  • Author: Hornum, Mads

    University of Copenhagen, Denmark

  • Author: Dirksen, Carsten

    University of Copenhagen, Denmark

  • Author: Svane, Maria

    University of Copenhagen, Denmark

  • Author: Gasbjerg, Lærke S.

    University of Copenhagen, Denmark

  • Author: Jørgensen, Nils B.

    University of Copenhagen, Denmark

  • Author: Gabe, Maria N.

    University of Copenhagen, Denmark

  • Author: Balk-Møller, Emilie

    University of Copenhagen, Denmark

  • Author: Albrechtsen, Reidar

    University of Copenhagen, Denmark

  • Author: Winther-Sørensen, Marie

    University of Copenhagen, Denmark

  • Author: Galsgaard, Katrine D.

    University of Copenhagen, Denmark

  • Author: Meissner, Felix

    Max Planck Institute of Biochemistry, Germany

  • Author: Jorsal, Tina

    University of Copenhagen, Denmark

  • Author: Lund, Asger

    University of Copenhagen, Denmark

  • Author: Vilsbøll, Tina

    University of Copenhagen, Denmark

  • Author: Eliasen, Rasmus

    Center for Nanomedicine and Theranostics, Centers, Colloids and Biological Interfaces, Department of Micro- and Nanotechnology, Technical University of Denmark, Produktionstorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Bojsen-Møller, Kirstine N.

    University of Copenhagen, Denmark

  • Author: Idorn, Thomas

    University of Copenhagen, Denmark

  • Author: Deacon, Carolyn F.

    University of Copenhagen, Denmark

  • Author: Knop, Filip K.

    University of Copenhagen, Denmark

  • Author: Rosenkilde, Mette M.

    University of Copenhagen, Denmark

  • Author: Hartmann, Bolette

    University of Copenhagen, Denmark

  • Author: Feldt-Rasmussen, Bo

    University of Copenhagen, Denmark

  • Author: Mann, Matthias

    University of Copenhagen, Denmark

  • Author: Madsbad, Sten

    University of Copenhagen, Denmark

  • Author: Holst, Jens J.

    University of Copenhagen, Denmark

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Glucagon is secreted from pancreatic α cells, and hypersecretion (hyperglucagonemia) contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61) appears to be the most abundant form. PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after. Studies in hepatocytes and in β cells demonstrated that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in vivo. We conclude that glucagon variants, such as PG 1-61, may contribute to glucose regulation by stimulating hepatic glucose production and insulin secretion.
Original languageEnglish
JournalCell Reports
Volume21
Issue number6
Pages (from-to)1452-1460
ISSN2211-1247
DOIs
Publication statusPublished - 2017
CitationsWeb of Science® Times Cited: No match on DOI

    Research areas

  • GLP-1, L-cells, Alpha cells, Glucagon, Proglucagon, Proteomics

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