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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.

SUBMITTER: Singh S

PROVIDER: S-EPMC4517591 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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ALDH1B1 links alcohol consumption and diabetes.

Singh Surendra S Chen Ying Y Matsumoto Akiko A Orlicky David J DJ Dong Hongbin H Thompson David C DC Vasiliou Vasilis V

Biochemical and biophysical research communications 20150615 4

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 ...[more]

PMID: 26086111

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Project description:ImportanceCardiovascular benefits of mild to moderate alcohol consumption need to be validated in the context of behavioral changes. The benefits of reduced alcohol consumption among people who drink heavily across different subtypes of cardiovascular disease (CVD) are unclear.ObjectiveTo investigate the association between reduced alcohol consumption and risk of major adverse cardiovascular events (MACEs) in individuals who drink heavily across different CVD subtypes.Design, setting, and participantsThis cohort study analyzed data from the Korean National Health Insurance Service-Health Screening database and self-reported questionnaires. The nationally representative cohort comprised Korean citizens aged 40 to 79 years who had national health insurance coverage on December 31, 2002, and were included in the 2002 to 2003 National Health Screening Program. People who drank heavily who underwent serial health examinations over 2 consecutive periods (first period: 2005-2008; second period: 2009-2012) were included and analyzed between February and May 2023. Heavy drinking was defined as more than 4 drinks (56 g) per day or more than 14 drinks (196 g) per week for males and more than 3 drinks (42 g) per day or more than 7 drinks (98 g) per week for females.ExposuresHabitual change in heavy alcohol consumption during the second health examination period. People who drank heavily at baseline were categorized into 2 groups according to changes in alcohol consumption during the second health examination period as sustained heavy drinking or reduced drinking.Main outcomes and measuresThe primary outcome was the occurrence of MACEs, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death.ResultsOf the 21 011 participants with heavy alcohol consumption at baseline (18 963 males [90.3%]; mean [SD] age, 56.08 [6.16] years) included in the study, 14 220 (67.7%) sustained heavy drinking, whereas 6791 (32.2%) shifted to mild to moderate drinking. During the follow-up of 162 378 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACEs than the reduced drinking group (817 vs 675 per 100 000 person-years; log-rank P = .003). Reduced alcohol consumption was associated with a 23% lower risk of MACEs compared with sustained heavy drinking (propensity score matching hazard ratio [PSM HR], 0.77; 95% CI, 0.67-0.88). These benefits were mostly accounted for by a significant reduction in the incidence of angina (PSM HR, 0.70; 95% CI, 0.51-0.97) and ischemic stroke (PSM HR, 0.66; 95% CI, 0.51-0.86). The preventive attributes of reduced alcohol intake were consistently observed across various subgroups of participants.Conclusions and relevanceResults of this cohort study suggest that reducing alcohol consumption is associated with a decreased risk of future CVD, with the most pronounced benefits expected for angina and ischemic stroke.

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ALDH1B1 links alcohol consumption and diabetes.

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ALDH1B1 links alcohol consumption and diabetes.

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