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

• DOI: 10.1016/j.celrep.2017.10.034
• Publication Date: 2017-11-07T17:17:22Z
• Authors: Nicolai J. Wewer ...; Rune E. Kuhre; Daniel Hornburg; Christian Z. Jensen; Mads Hornum; Carsten Dirksen; Maria Svane; Lærke S. Gasbjerg; Nils B. Jørgensen; Maria N. Gabe; Emilie Balk-Møller; Reidar Albrechtsen; Marie Winther-Sør...; Katrine D. Galsgaard; Felix Meissner; Tina Jorsal; Asger Lund; Tina Vilsbøll; Rasmus Eliasen; Kirstine N. Bojse...; Thomas Idorn; Carolyn F. Deacon; Filip K. Knop; Mette M. Rosenkilde; Bolette Hartmann; Bo Feldt-Rasmussen; Matthias Mann; Sten Madsbad; Jens J. Holst
• Keywords: Hyperglucagonemia; Proglucagon; Glycogenolysis; Gluconeogenesis; Glucokinase

Glucagon is secreted from pancreatic α cells, and hypersecretion (hyperglucagonemia) contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61) appears be the most abundant form. PG subjects with obesity, both before after gastric bypass surgery, protein fat as main drivers for secretion but glucose after. Studies hepatocytes β cells demonstrated that dose-dependently increases levels of cAMP, through receptor, insulin enzymes regulating glycogenolysis gluconeogenesis. In rats, blood decreases amino acids vivo. We conclude such 1-61, may contribute regulation by stimulating hepatic production secretion.