title: ALDH1B1 links alcohol consumption and diabetes.
abstract: Aldehyde dehydrogenase 1B1 (ALDH1B1) is a mitochondrial enzyme sharing 65% and 72% sequence identity with ALDH1A1 and ALDH2 proteins, respectively. Compared to the latter two ALDH isozymes, little is known about the physiological functions of ALDH1B1. Studies in humans indicate that ALDH1B1 may be associated with alcohol sensitivity and stem cells. Our recent in vitro studies using human ALDH1B1 showed that it metabolizes acetaldehyde and retinaldehyde. To investigate the in vivo role of ALDH1B1, we generated and characterized a global Aldh1b1 knockout mouse line. These knockout (KO) mice are fertile and show overtly good health. However, ethanol pharmacokinetic analysis revealed ∼40% increase in blood acetaldehyde levels in KO mice. Interestingly, the KO mice exhibited higher fasting blood glucose levels. Collectively, we show for the first time the functional in vivo role of ALDH1B1 in acetaldehyde metabolism and in maintaining glucose homeostasis. This mouse model is a valuable tool to investigate the mechanism by which alcohol may promote the development of diabetes.
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
authors.forename: Surendra
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06520.|Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
authors.forename: David J
authors.initials: DJ
authors.lastname: Orlicky
authors.affiliation: Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06520.|Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Clinical Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
authors.forename: David C
authors.initials: DC
authors.lastname: Thompson
authors.affiliation: Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06520.|Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Vasiliou
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D000431:Ethanol; D000080924:Aldehyde Dehydrogenase 1 Family; C578830:ALDH1B1 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D005947:Glucose
keywords: ALDH1B1; Acetaldehyde; Colon; Ethanol; Glucose; Pancreas