Department of Pediatrics and Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
Can J Physiol Pharmacol. 2012 Dec;90(12):1642-6. doi: 10.1139/y2012-131. Epub 2012 Nov 23.
Type 1 diabetic patients have hyperketonemia, elevated levels of pro-inflammatory and oxidative stress markers, and a higher incidence of vascular disease. This study examines the hypothesis that hyperketonemia increases reactive oxygen species (ROS) and is in part responsible for increased expression of adhesion molecules in monocytes. THP-1 monocytes were treated with acetoacetate (AA) or β-hydroxybutyrate (BHB) (0-10 mmol/L) for 24 h. Results show that AA, but not BHB, increases ROS production in monocytes. Pretreatment of monocytes with N-acetylcysteine (NAC) inhibited AA-induced ROS production. AA treatment induced upregulation of LFA-1 and pretreatment of monocytes with NAC or an inhibitor to p38 MAPK inhibited this upregulation in monocytes. This suggests that physiological concentrations of AA can contribute to increased ROS and activation of p38 MAPK, which may be responsible for AA-induced upregulation of LFA-1 in monocytes. Thus, hyperketonemia contributes to the risk for cardiovascular disease in type 1 diabetes.
1 型糖尿病患者存在酮血症、促炎和氧化应激标志物水平升高，以及血管疾病发生率更高的情况。本研究检验了这样一个假设，即酮血症会增加活性氧（ROS），并在一定程度上导致单核细胞中黏附分子表达增加。将 THP-1 单核细胞用乙酰乙酸（AA）或β-羟丁酸（BHB）（0-10mmol/L）处理 24 小时。结果表明，AA 而非 BHB 可增加单核细胞中的 ROS 产生。用 N-乙酰半胱氨酸（NAC）预处理单核细胞可抑制 AA 诱导的 ROS 产生。AA 处理诱导 LFA-1 的上调，而用 NAC 或 p38 MAPK 的抑制剂预处理单核细胞可抑制这种上调。这表明，生理浓度的 AA 可导致 ROS 和 p38 MAPK 的激活增加，这可能是 AA 诱导单核细胞中 LFA-1 上调的原因。因此，酮血症会增加 1 型糖尿病患者发生心血管疾病的风险。
