@article{9195da6df5594f0b9ac6781e931fa687,
title = "Recent advances in understanding the complexity of alcohol-induced pancreatic dysfunction and pancreatitis development",
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.",
keywords = "Alcohol, Autophagy, Endoplasmic reticulum stress, Fatty acid ethyl esters, Lysosome, Pancreatitis, Transcription factor EB (TFEB)",
author = "Karuna Rasineni and Srinivasan, {Mukund P.} and Balamurugan, {Appakalai N.} and Kaphalia, {Bhupendra S.} and Shaogui Wang and Ding, {Wen Xing} and Pandol, {Stephen J.} and Aurelia Lugea and Liz Simon and Molina, {Patricia E.} and Peter Gao and Casey, {Carol A.} and Osna, {Natalia A.} and Kharbanda, {Kusum K.}",
note = "Funding Information: Author Contributions: K.K.K. and K.R. have both contributed to topic outset, review of the literature, writing of (W.X.D), R01 DK102142 (W.X.D), R01 AA024464 (S.J.P), R01 AA019954 (A.L), U01 AA024733 (W.X.D), U01 the manuscript and approval of the final version. M.P.S., A.N.B., B.S.K., S.W., W.-X.D., S.J.P., A.L., L.S., P.E.M., P.G., C.A.C. and N.A.O. provided important academic content and critical review. All authors have read and agreed to the published version of the manuscript. Conflicts of Interest: The authors have no conflicts of interest. Funding: This work was supported by Merit Review grants, BX004053 (K.K.K.), BX 004171 (C.A.C.) from the U.S. Department of Veterans Affairs, Biomedical Laboratory Research and Development Service, and the National Institutes of Health under award numbers K01 AA024494 (L.S.), K01 AA024254 (K.R.), R21 AA026428 (K.K.K.), R21 AA024699 (B.S.K.), R01 AA026723 (K.K.K.), R01 AA 02073506 (C.A.C.), R01 AA025850 (B.S.K.), R01 AA020518 (W.-X.D.), R01 DK102142 (W.-X.D.), R01 AA024464 (S.J.P.), R01 AA019954 (A.L.), U01 AA024733 (W.-X.D.), U01 DK108314 (S.J.P.), P01 DK098108 (S.J.P.), and P60 AA009803 (P.M.). Funding Information: Based on these considerations, it is predicted that agents that can reduce ER stress and improve autophagic mechanisms may be beneficial for preventing or treating pancreatitis. Further, lifestyle Funding: This work was supported by Merit Review grants, BX004053 (K.K.K), BX 004171 (C.A.C) from the U.S. modifications including exercise or diet interventions could also improve both exocrine and endocrine Department of Veterans Affairs, Biomedical Laboratory Research and Development Service, and the National Institutes of Health under award numbers K01 AA024494 (L.S), K01 AA024254 (K.R), R21 AA026428 (K.K.K), R21 AA024699 (B.S.K), R01 AA026723 (K.K.K), R01 AA 02073506 (C.A.C), R01 AA025850 (B.S.K), R01 AA020518 Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = may,
doi = "10.3390/biom10050669",
language = "English (US)",
volume = "10",
journal = "Biomolecules",
issn = "2218-273X",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "5",
}