Hepatic activating transcription factor 3 (ATF3) may play an important role in oxidative stress-mediated hepatic steatosis and the development of type 2 diabetes (T2D) in a Zucker diabetic fatty (ZDF) rat model and in human patients with non-alcoholic fatty liver disease (NAFLD). Therefore, ATF3 may be a useful biomarker for predicting the progression of NAFLD and the development of T2D. Furthermore, given the significant association between hepatic ATF3 expression and both hepatic steatosis and impaired glucose homeostasis, in vivo ATF3 silencing may be a potential central strategy for preventing and managing NAFLD and T2D.
Moderate alcohol consumption is generally associated with reduced risk of type 2 diabetes. However, this beneficial effects of alcohol intake remains controversial due to inconsistent results across studies. The analysis was performed using data from the Ansung-Ansan cohort study. We categorized the participants into four groups—based on the baseline (one-point measure; non-drinking, <5 g/day, ≥5, <30 g/day, and ≥30 g/day) and follow-up (consumption pattern; never-drinking, light, moderate, and heavy drinking) measurement. At baseline, ≥30 g/day alcohol consumption increased the risk of incident diabetes (HR: 1.42; 95% CI, 1.10–1.85), but ≥5, <30 g/day alcohol consumption had no effects on the incident diabetes. Meanwhile, when using the alcohol consumption pattern, a heavy-drinking pattern increased the risk of incident diabetes (HR = 1.32, 1.01–1.73), but the light and moderate consumption pattern was associated with a reduced risk of type 2 diabetes (HR: 0.66; 0.50–0.87 and HR: 0.74; 0.57–0.95, respectively). At the end point of follow-up, the insulinogenic index (IGI), but not the insulin sensitivity index (ISI), differed among the groups. Alcohol consumption pattern had a J-shaped association with the incident type 2 diabetes in Korean men. The IGI showed an inverted J-shaped association according to alcohol drinking pattern, but the ISI was not a J-shape.
Background: Chronic ethanol consumption induces pancreatic β-cell dysfunction and metabolic syndrome.Results: Ethanol-induced Atf3 inhibits glucokinase transcriptional activity through direct binding or Atf3/Pdx-1/Hdac1 axis on glucokinase promoter.Conclusion: ATf3 fosters β-cell dysfunction via Gck down-regulation and triggers T2D, which is ameliorated by in vivo Atf3 silencing.Significance: The presented data uncover a new role for Atf3 as a potential therapeutic target in treating type 2 diabetes.
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