TY - JOUR
T1 - Glucagon-like peptide-1 receptor signaling in acinar cells causes growth dependent release of pancreatic enzymes
AU - Albrechtsen, Nicolai Jacob Wewer
AU - Albrechtsen, Reidar
AU - Bremholm, l
AU - Svendsen, Berit
AU - Kuhre, Rune Ehrenreich
AU - Poulsen, Steen Seier
AU - Christiansen, Charlotte Bayer
AU - Jensen, Elisa Pouline
AU - Janus, Charlotte
AU - Hilsted, Linda
AU - Deacon, Carolyn F.
AU - Hartmann, Bolette
AU - Holst, Jens Juul
PY - 2016
Y1 - 2016
N2 - Incretin-based therapies are widely used for type 2 diabetes and now also for obesity, but they are associated with elevated plasma levels of pancreatic enzymes and perhaps a modestly increased risk of acute pancreatitis. However, little is known about the effects of the incretin hormone glucagon-like peptide 1 (GLP-1) on the exocrine pancreas. Here, we identify GLP-1 receptors on pancreatic acini and analyze the impact of receptor activation in humans, rodents, isolated acini, and cell lines from the exocrine pancreas. GLP-1 did not directly stimulate amylase or lipase release. However, we saw that GLP-1 induces phosphorylation of the epidermal growth factor receptor and activation of Foxo1, resulting in cell growth with concomitant enzyme release. Our work uncovers GLP-1-induced signaling pathways in the exocrine pancreas and suggests that increases in amylase and lipase levels in subjects treated with GLP-1 receptor agonists reflect adaptive growth rather than early-stage pancreatitis.
AB - Incretin-based therapies are widely used for type 2 diabetes and now also for obesity, but they are associated with elevated plasma levels of pancreatic enzymes and perhaps a modestly increased risk of acute pancreatitis. However, little is known about the effects of the incretin hormone glucagon-like peptide 1 (GLP-1) on the exocrine pancreas. Here, we identify GLP-1 receptors on pancreatic acini and analyze the impact of receptor activation in humans, rodents, isolated acini, and cell lines from the exocrine pancreas. GLP-1 did not directly stimulate amylase or lipase release. However, we saw that GLP-1 induces phosphorylation of the epidermal growth factor receptor and activation of Foxo1, resulting in cell growth with concomitant enzyme release. Our work uncovers GLP-1-induced signaling pathways in the exocrine pancreas and suggests that increases in amylase and lipase levels in subjects treated with GLP-1 receptor agonists reflect adaptive growth rather than early-stage pancreatitis.
U2 - 10.1016/j.celrep.2016.11.051
DO - 10.1016/j.celrep.2016.11.051
M3 - Journal article
C2 - 27974199
VL - 17
SP - 2845
EP - 2856
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 11
ER -