Galactose protects against cell damage in mouse models of acute pancreatitis

Peng, Shuang, Gerasimenko, Julia V. ORCID: https://orcid.org/0000-0002-2262-2543, Tsugorka, Tetyana M., Gryshchenko, Oleksiy, Samarasinghe, Sujith, Petersen, Ole H. ORCID: https://orcid.org/0000-0002-6998-0380 and Gerasimenko, Oleg V. ORCID: https://orcid.org/0000-0003-2573-8258 2018. Galactose protects against cell damage in mouse models of acute pancreatitis. Journal of Clinical Investigation 128 (9) , pp. 3769-3778. 10.1172/JCI94714

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (7MB) | Preview

Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Additional Information:	This work is licensed under the Creative Commons Attribution 4.0 International License.
Publisher:	American Society for Clinical Investigation
ISSN:	0021-9738
Date of First Compliant Deposit:	20 June 2018
Date of Acceptance:	6 June 2018
Last Modified:	11 May 2023 03:41
URI:	https://orca.cardiff.ac.uk/id/eprint/112599

Citation Data

Cited 27 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item