ArticleThe Journal of biological chemistry2010
Chronic ethanol consumption-induced pancreatic {beta}-cell dysfunction and apoptosis through glucokinase nitration and its down-regulation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 94 citations in OpenAlex.
- Alcohol and the endocrine system: A critical review of disruptions, potential mechanisms, and health implications.Alcohol, clinical & experimental research · 2026Review
- Oxidative Stress in Liver Metabolic Dysfunction and Diseases, with a Focus on Hepatogenic Diabetes: Effect of Alcohol Consumption.Antioxidants (Basel, Switzerland) · 2025Review
- Physiological Mechanisms Vulnerable to Alcohol-Induced Alterations: Role in Chronic Comorbidities.Comprehensive Physiology · 2025Review
- The association between metabolic syndrome severity and frailty risk in patients with rheumatoid arthritis: a cross-sectional study.Arthritis research & therapy · 2025Article
- Crocin and gallic acid attenuate ethanol-induced mitochondrial dysfunction via suppression of ROS formation and inhibition of mitochondrial swelling in pancreatic mitochondria.Molecular and cellular biochemistry · 2025Article
- L-arginine administration exacerbates myocardial injury in diabeticsWorld journal of diabetes · 2025Article
- Excessive alcohol consumption: a driver of metabolic dysfunction and inflammation.Frontiers in toxicology · 2025Review
- Interactions of genes with alcohol consumption affect insulin sensitivity and beta cell function.Diabetologia · 2025Article
- Effect of diabetes on mortality and liver transplantation in alcoholic liver cirrhotic patients with acute decompensation.Hepatology international · 2024Article
- Activating transcription factor 3, glucolipid metabolism, and metabolic diseases.Journal of molecular cell biology · 2023Article
- Current Knowledge on the Pathophysiology of Lean/Normal-Weight Type 2 Diabetes.International journal of molecular sciences · 2022Review
- Impact of Reactive Species on Amino Acids-Biological Relevance in Proteins and Induced Pathologies.International journal of molecular sciences · 2022Review
- Hepatogenous diabetes: Knowledge, evidence, and skepticism.World journal of hepatology · 2022Review
- Arginase: Biological and Therapeutic Implications in Diabetes Mellitus and Its Complications.Oxidative medicine and cellular longevity · 2022Review
- Binge alcohol drinking before pregnancy is closely associated with the development of macrosomia: Korean pregnancy registry cohort.PloS one · 2022Article
- Cellular Bioenergetics: Experimental Evidence for Alcohol-induced Adaptations.Function (Oxford, England) · 2022Review
- Chronic binge alcohol and ovariectomy-mediated impaired insulin responsiveness in SIV-infected female rhesus macaques.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Alcohol and Metabolic-associated Fatty Liver Disease.Journal of clinical and translational hepatology · 2021Review
- A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
- Pathophysiological Consequences of At-Risk Alcohol Use; Implications for Comorbidity Risk in Persons Living With Human Immunodeficiency Virus.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic ethanol consumption is known as an independent risk factor for type 2 diabetes, which is characterized by impaired glucose homeostasis and insulin resistance; however, there is a great deal of controversy concerning the relationships between alcohol consumption and the development of type 2 diabetes. We investigated the effects of chronic ethanol consumption on pancreatic β-cell dysfunction and whether generated peroxynitrite participates in the impaired glucose homeostasis. Here we show that chronic ethanol feeding decreases the ability of pancreatic β-cells to mediate insulin secretion and ATP production in coordination with the decrease of glucokinase, Glut2, and insulin expression. Specific blockade of ATF3 using siRNA or C-terminally deleted ATF3(ΔC) attenuated ethanol-induced pancreatic β-cell apoptosis or dysfunction and restored the down-regulation of glucokinase (GCK), insulin, and pancreatic duodenal homeobox-1 induced by ethanol. GCK inactivation and down-regulation were predominantly mediated by ethanol metabolism-generated peroxynitrite, which were suppressed by the peroxynitrite scavengers N(γ)-monomethyl-L-arginine, uric acid, and deferoxamine but not by the S-nitrosylation inhibitor DTT, indicating that tyrosine nitration is the predominant modification associated with GCK down-regulation and inactivation rather than S-nitrosylation of cysteine. Tyrosine nitration of GCK prevented its association with pBad, and GCK translocation into the mitochondria results in subsequent proteasomal degradation of GCK following ubiquitination. This study identified a novel and efficient pathway by which chronic ethanol consumption may induce GCK down-regulation and inactivation by inducing tyrosine nitration of GCK, resulting in pancreatic β-cell apoptosis and dysfunction. Peroxynitrite-induced ATF3 may also serve as a potent upstream regulator of GCK down-regulation and β-cell apoptosis.
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