ALDH1B1 links alcohol consumption and diabetes

• Published in: Biochemical and biophysical research communications 2015-08, Vol.463 (4), p.768-773
• Main Authors: Singh, Surendra, Chen, Ying, Matsumoto, Akiko, Orlicky, David J., Dong, Hongbin, Thompson, David C., Vasiliou, Vasilis
• Format: Article
• Language: English
• Subjects: Acetaldehyde; alcohol drinking; Alcohol Drinking - genetics; aldehyde dehydrogenase; Aldehyde Dehydrogenase - genetics; Aldehyde Dehydrogenase - metabolism; Aldehyde Dehydrogenase 1 Family; Aldehyde Dehydrogenase, Mitochondrial; ALDH1B1; animal models; Animals; Base Sequence; blood; blood glucose; Colon; diabetes; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; DNA Primers; Ethanol; Ethanol - metabolism; fasting; Glucose; Glucose - metabolism; Homeostasis; humans; in vitro studies; isozymes; knockout mutants; Mice; Mice, Knockout; mitochondria; Pancreas; pharmacokinetics; proteins; Real-Time Polymerase Chain Reaction; retinaldehyde; Reverse Transcriptase Polymerase Chain Reaction; sequence analysis; stem cells
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.06.011

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. •Establishment of Aldh1b1 knockout (KO) mice, which develop normally and show overtly good health.•Ethanol pharmacokinetic analysis revealed ∼40% increase in blood acetaldehyde levels in KO mice.•KO mice exhibit higher fasting blood glucose levels.