Glucagon-like Peptide 1 Receptor Signaling in Acinar Cells Causes Growth-Dependent Release of Pancreatic Enzymes

Publication date: 13 December 2016
Source:Cell Reports, Volume 17, Issue 11
Author(s): Nicolai J. Wewer Albrechtsen, Reidar Albrechtsen, Lasse Bremholm, Berit Svendsen, Rune E. Kuhre, Steen S. Poulsen, Charlotte B. Christiansen, Elisa P. Jensen, Charlotte Janus, Linda Hilsted, Carolyn F. Deacon, Bolette Hartmann, Jens J. Holst
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.

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Teaser

Glucagon-like peptide 1 (GLP-1)-based therapies are used to treat type 2 diabetes and obesity. Wewer Albrechtsen et al. detect GLP-1 receptor expression in pancreatic acinar cells and show that its activation leads to mild c-Src-dependent proliferation, increasing constitutive enzyme release. This enzyme increase during GLP-1 treatment does not reflect sub-clinical pancreatitis.


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