Glucagon-like peptide-1 receptor signaling in acinar cells causes growth dependent release of pancreatic enzymes

Nicolai Jacob Wewer Albrechtsen; Reidar Albrechtsen; l Bremholm; Berit Svendsen; Rune Ehrenreich Kuhre; Steen Seier Poulsen; Charlotte Bayer Christiansen; Elisa Pouline Jensen; Charlotte Janus; Linda Hilsted; Carolyn F. Deacon; Bolette Hartmann; Jens Juul Holst

doi:10.1016/j.celrep.2016.11.051

Glucagon-like peptide-1 receptor signaling in acinar cells causes growth dependent release of pancreatic enzymes

Nicolai Jacob Wewer Albrechtsen, Reidar Albrechtsen, l Bremholm, Berit Svendsen, Rune Ehrenreich Kuhre, Steen Seier Poulsen, Charlotte Bayer Christiansen, Elisa Pouline Jensen, Charlotte Janus, Linda Hilsted, Carolyn F. Deacon, Bolette Hartmann, Jens Juul Holst

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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.

Original language	English
Journal	Cell Reports
Volume	17
Issue number	11
Pages (from-to)	2845-2856
Number of pages	13
DOIs	https://doi.org/10.1016/j.celrep.2016.11.051
Publication status	Published - 13 Dec 2016

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Glucagon-like Peptide 1 Receptor Signaling in Acinar Cells Causes Growth-Dependent Release of Pancreatic EnzymesFinal published version, 4.07 MBLicence: CC BY-NC-ND

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Albrechtsen, N. J. W., Albrechtsen, R., Bremholm, L., Svendsen, B., Kuhre, R. E., Poulsen, S. S., Christiansen, C. B., Jensen, E. P., Janus, C., Hilsted, L., Deacon, C. F., Hartmann, B., & Holst, J. J. (2016). Glucagon-like peptide-1 receptor signaling in acinar cells causes growth dependent release of pancreatic enzymes. Cell Reports, 17(11), 2845-2856. https://doi.org/10.1016/j.celrep.2016.11.051

Albrechtsen, NJW , Albrechtsen, R, Bremholm, L, Svendsen, B, Kuhre, RE , Poulsen, SS , Christiansen, CB, Jensen, EP, Janus, C, Hilsted, L , Deacon, CF , Hartmann, B & Holst, JJ 2016, 'Glucagon-like peptide-1 receptor signaling in acinar cells causes growth dependent release of pancreatic enzymes', Cell Reports, vol. 17, no. 11, pp. 2845-2856. https://doi.org/10.1016/j.celrep.2016.11.051

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title = "Glucagon-like peptide-1 receptor signaling in acinar cells causes growth dependent release of pancreatic enzymes",

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.",

author = "Albrechtsen, {Nicolai Jacob Wewer} and Reidar Albrechtsen and l Bremholm and Berit Svendsen and Kuhre, {Rune Ehrenreich} and Poulsen, {Steen Seier} and Christiansen, {Charlotte Bayer} and Jensen, {Elisa Pouline} and Charlotte Janus and Linda Hilsted and Deacon, {Carolyn F.} and Bolette Hartmann and Holst, {Jens Juul}",

year = "2016",

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doi = "10.1016/j.celrep.2016.11.051",

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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 - 2016/12/13

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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.

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DO - 10.1016/j.celrep.2016.11.051

M3 - Journal article

C2 - 27974199

SN - 2211-1247

VL - 17

SP - 2845

EP - 2856

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -

Glucagon-like peptide-1 receptor signaling in acinar cells causes growth dependent release of pancreatic enzymes

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