The role of free fatty acids, pancreatic lipase and Ca 2+ signalling in injury of isolated acinar cells and pancreatitis model in lipoprotein lipase‐deficient mice
Abstract
AIM AND METHODS: Recurrent pancreatitis is a common complication of severe hypertriglyceridaemia (HTG) often seen in patients carrying various gene mutations in lipoprotein lipase (LPL). This study investigates a possible pathogenic mechanism of cell damage in isolated mouse pancreatic acinar cells and of pancreatitis in LPL-deficient and in wild type mice. RESULTS: Addition of free fatty acids (FFA) or of chylomicrons to isolated pancreatic acinar cells caused stimulation of amylase release, and at higher concentrations it also caused cell damage. This effect was decreased in the presence of the lipase inhibitor orlistat. Surprisingly, pancreatic lipase whether in its active or inactive state could act like an agonist by inducing amylase secretion, increasing cellular cGMP levels and converting cell damaging sustained elevations of [Ca(2+)](cyt) to normal Ca(2+) oscillations. Caerulein increases the levels of serum amylase and caused more severe inflammation in the pancreas of LPL-deficient mice than in wild type mice. CONCLUSION: We conclude that high concentrations of FFA as present in the plasma of LPL-deficient mice and in patients with HTG lead to pancreatic cell damage and are high risk factors for the development of acute pancreatitis. In addition to its enzymatic effect which leads to the generation of cell-damaging FFA from triglycerides, pancreatic lipase also prevents Ca(2+) overload in pancreatic acinar cells and, therefore, counteracts cell injury.
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Acute pancreatitis can lead to chronic pancreatitis, signs of exocrine or endocrine pancreatic insufficiency, including pancreatic (type 3c) diabetes, and can be fatal.
“Acute pancreatitis can lead to chronic pancreatitis, 10,11 signs of exocrine or endocrine pancreatic insufficiency, including pancreatic (type 3c) diabetes, 12 and can be fatal.”
From Familial chylomicronemia syndrome: Bringing to life dietary recommendations throughout the life span (2018) · cites this paper as [10]
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- Authors
- Yang, F., Wang, Y., Sternfeld, L., Rodriguez, J. A., Ross, C., Hayden, M. R., Carriere, F., Liu, G., & Schulz, I.
- Affiliations
- Saarland University (DE)
- Peking University (CN)
- University of British Columbia (CA)
- Corresponding author
- Liu, G.
- Schulz, I.
- Venue
- Acta Physiologica
- Publisher
- Wiley
- Published
- 2008-12-09
- Volume
- 195
- Issue
- 1
- Pages
- 13-28
- ISSN
- 1748-1708 (ISSN-L)
- 1748-1716
- OpenAlex
- W2019825486
- Cited by
- 93
- References
- 42
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 7 · 2020: 10 · 2019: 2 · 2018: 9 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 3 · 2012: 4
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Physiologica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- lipoprotein lipase deficiency, hypertriglyceridemia, acute pancreatitis, free fatty acids, pancreatic acinar cells, pancreatic lipase, calcium signaling, calcium oscillations, cyclic GMP, orlistat, chylomicrons, amylase secretion, caerulein, lipase inhibitors
- MeSH terms
- Animals, Calcium, Cells, Cultured, Cholecystokinin, Chylomicrons, Dose-Response Relationship, Drug, Fatty Acids, Nonesterified, L-Lactate Dehydrogenase, Lipase, Lipoprotein Lipase, Pancreas, Pancreatitis, Signal Transduction, Gene Expression Regulation, Enzymologic, Calcium Signaling, Mice
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