TY - JOUR
T1 - Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production
AU - Albrechtsen, Nicolai J. Wewer
AU - Kuhre, Rune E.
AU - Hornburg, Daniel
AU - Jensen, Christian Z.
AU - Hornum, Mads
AU - Dirksen, Carsten
AU - Svane, Maria
AU - Gasbjerg, Laerke S.
AU - Jorgensen, Nils B.
AU - Gabe, Maria N.
AU - Balk-Moller, Emilie
AU - Albrechtsen, Reidar
AU - Winther-Sorensen, Marie
AU - Galsgaard, Katrine D.
AU - Meissner, Felix
AU - Jorsal, Tina
AU - Lund, Asger
AU - Vilsboll, Tina
AU - Eliasen, Rasmus
AU - Bojsen-Moller, Kirstine N.
AU - Idorn, Thomas
AU - Deacon, Carolyn F.
AU - Knop, Filip K.
AU - Rosenkilde, Mette M.
AU - Hartmann, Bolette
AU - Feldt-Rasmussen, Bo
AU - Mann, Matthias
AU - Madsbad, Sten
AU - Holst, Jens J.
PY - 2017/11
Y1 - 2017/11
N2 - 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.
AB - 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.
U2 - 10.1016/j.celrep.2017.10.034
DO - 10.1016/j.celrep.2017.10.034
M3 - Journal article
C2 - 29117552
VL - 21
SP - 1452
EP - 1460
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 6
ER -