Galactose protects against cell damage in mouse models of acute pancreatitis

Acute pancreatitis (AP), a human disease in which the pancreas digests itself, has substantial mortality with no specific therapy. The major causes of AP are alcohol abuse and gallstone complications, but it also occurs as an important side effect of the standard asparaginase-based therapy for child...

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Bibliographic Details
Published in:The Journal of clinical investigation 2018-09, Vol.128 (9), p.3769-3778
Main Authors: Peng, Shuang, Gerasimenko, Julia V, Tsugorka, Tetyana M, Gryshchenko, Oleksiy, Samarasinghe, Sujith, Petersen, Ole H, Gerasimenko, Oleg V
Format: Article
Language:English
Subjects:
Abuse
Acinar cells
Acute lymphoblastic leukemia
Alcohol
Alcohol abuse
Animal models
Apoptosis
Asparaginase
Bile acids
Biomedical research
Calculi
Care and treatment
Cell culture
Cell death
Children
Development and progression
Enzymes
Ethanol
Fatty acids
Galactose
Gallstones
Gangrene
Glucose metabolism
Health aspects
Insulin
Leukemia
Lymphatic leukemia
Medical research
Metabolism
Metabolites
Necrosis
Pancreas
Pancreatitis
Permeability
Pyruvic acid
Rodents
Signal transduction
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Summary:Acute pancreatitis (AP), a human disease in which the pancreas digests itself, has substantial mortality with no specific therapy. The major causes of AP are alcohol abuse and gallstone complications, but it also occurs as an important side effect of the standard asparaginase-based therapy for childhood acute lymphoblastic leukemia. Previous investigations into the mechanisms underlying pancreatic acinar cell death induced by alcohol metabolites, bile acids, or asparaginase indicated that loss of intracellular ATP generation is an important factor. We now report that, in isolated mouse pancreatic acinar cells or cell clusters, removal of extracellular glucose had little effect on this ATP loss, suggesting that glucose metabolism was severely inhibited under these conditions. Surprisingly, we show that replacing glucose with galactose prevented or markedly reduced the loss of ATP and any subsequent necrosis. Addition of pyruvate had a similar protective effect. We also studied the effect of galactose in vivo in mouse models of AP induced either by a combination of fatty acids and ethanol or asparaginase. In both cases, galactose markedly reduced acinar necrosis and inflammation. Based on these data, we suggest that galactose feeding may be used to protect against AP.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI94714