Glucagon-like Peptide 1 Receptor Signaling in Acinar Cells Causes Growth-Dependent Release of Pancreatic Enzymes.
Cell Rep
; 17(11): 2845-2856, 2016 12 13.
Article
em En
| MEDLINE
| ID: mdl-27974199
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeo 1 Semelhante ao Glucagon
/
Receptor do Peptídeo Semelhante ao Glucagon 1
/
Proteína Forkhead Box O1
/
Amilases
/
Lipase
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article