Glucagon-like peptide-1 receptor is present in pancreatic acinar cells and regulates amylase secretion through cAMP

Am J Physiol Gastrointest Liver Physiol. 2016 Jan 1;310(1):G26-33. doi: 10.1152/ajpgi.00293.2015. Epub 2015 Nov 5.


Glucagon-like peptide-1 (GLP-1) is a glucoincretin hormone that can act through its receptor (GLP-1R) on pancreatic β-cells and increase insulin secretion and production. GLP-1R agonists are used clinically to treat type 2 diabetes. GLP-1 may also regulate the exocrine pancreas at multiple levels, including inhibition through the central nervous system, stimulation indirectly through insulin, and stimulation directly on acinar cells. However, it has been unclear whether GLP-1R is present in pancreatic acini and what physiological functions these receptors regulate. In the current study we utilized GLP-1R knockout (KO) mice to study the role of GLP-1R in acinar cells. RNA expression of GLP-1R was detected in acutely isolated pancreatic acini. Acinar cell morphology and expression of digestive enzymes were not affected by loss of GLP-1R. GLP-1 induced amylase secretion in wild-type (WT) acini. In GLP-1R KO mice, this effect was abolished, whereas vasoactive intestinal peptide-induced amylase release in KO acini showed a pattern similar to that in WT acini. GLP-1 stimulated cAMP production and increased protein kinase A-mediated protein phosphorylation in WT acini, and these effects were absent in KO acini. These data show that GLP-1R is present in pancreatic acinar cells and that GLP-1 can regulate secretion through its receptor and cAMP signaling pathway.

Keywords: amylase secretion; cAMP; glucagon-like peptide-1 receptor; pancreatic acini.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acinar Cells / enzymology*
  • Acinar Cells / metabolism
  • Amylases / metabolism*
  • Animals
  • Cell Shape
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dose-Response Relationship, Drug
  • Glucagon-Like Peptide 1 / pharmacology
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucagon-Like Peptide-1 Receptor / deficiency
  • Glucagon-Like Peptide-1 Receptor / genetics
  • Glucagon-Like Peptide-1 Receptor / metabolism*
  • Incretins / pharmacology
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / enzymology*
  • Islets of Langerhans / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphorylation
  • RNA, Messenger / metabolism
  • Second Messenger Systems


  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Incretins
  • RNA, Messenger
  • Glucagon-Like Peptide 1
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Amylases