Recent advances in understanding the complexity of alcohol-induced pancreatic dysfunction and pancreatitis development

Karuna Rasineni, Mukund P. Srinivasan, Appakalai N. Balamurugan, Bhupendra S. Kaphalia, Shaogui Wang, Wen Xing Ding, Stephen J. Pandol, Aurelia Lugea, Liz Simon, Patricia E. Molina, Peter Gao, Carol A. Casey, Natalia A. Osna, Kusum K. Kharbanda

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Chronic excessive alcohol use is a well-recognized risk factor for pancreatic dysfunction and pancreatitis development. Evidence from in vivo and in vitro studies indicates that the detrimental effects of alcohol on the pancreas are from the direct toxic effects of metabolites and byproducts of ethanol metabolism such as reactive oxygen species. Pancreatic dysfunction and pancreatitis development are now increasingly thought to be multifactorial conditions, where alcohol, genetics, lifestyle, and infectious agents may determine the initiation and course of the disease. In this review, we first highlight the role of nonoxidative ethanol metabolism in the generation and accumulation of fatty acid ethyl esters (FAEEs) that cause multi-organellar dysfunction in the pancreas which ultimately leads to pancreatitis development. Further, we discuss how alcohol-mediated altered autophagy leads to the development of pancreatitis. We also provide insights into how alcohol interactions with other co-morbidities such as smoking or viral infections may negatively affect exocrine and endocrine pancreatic function. Finally, we present potential strategies to ameliorate organellar dysfunction which could attenuate pancreatic dysfunction and pancreatitis severity.

Original languageEnglish (US)
Article number669
JournalBiomolecules
Volume10
Issue number5
DOIs
StatePublished - May 2020

Keywords

  • Alcohol
  • Autophagy
  • Endoplasmic reticulum stress
  • Fatty acid ethyl esters
  • Lysosome
  • Pancreatitis
  • Transcription factor EB (TFEB)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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