Jain S K, Kannan K, McVie R
Department of Pediatrics, Louisiana State University Medical Center, Shreveport, Louisiana 71130, USA.
Antioxid Redox Signal. 1999 Summer;1(2):211-20. doi: 10.1089/ars.1999.1.2-211.
Recent studies have proposed a role for a reduced number of circulating monocytes in the development of atherosclerosis and circulatory diseases in diabetes. Ketosis is frequently encountered in type-I diabetics. This study was undertaken to test the hypothesis that hyperketonemia can lower blood monocyte count in type-I diabetic patients. Blood monocyte count was significantly lower (p < 0.05) in diabetics (n = 27) compared with age-matched normal siblings (n = 22). Blood levels of acetoacetate (AA) and triglycerides were significantly higher in diabetics compared with normals. To examine whether hyperketonemia can directly alter the monocyte count in diabetics, we studied the effect of ketone bodies AA and beta-hydroxybutyrate (BHB) on U937 cells, a human-derived promonocytic cell line as an in vitro model. The cell culture studies showed a dose-dependent growth inhibition and induction of apoptosis as a result of treatment with AA in U937 cells. Furthermore, there was a significant decrease in GSH and increase in lipid peroxidation products in AA-treated U937 cells. Taken together, this study suggests that elevated levels of ketone body AA can result in oxidative damage, accelerated apoptosis, and inhibition of cell growth in monocytes, which in turn can lower monocyte count in the blood of type-I diabetic patients.
最近的研究表明，循环单核细胞数量减少在糖尿病患者动脉粥样硬化和循环系统疾病的发生中起一定作用。I型糖尿病患者经常出现酮症。本研究旨在验证高酮血症可降低I型糖尿病患者血液单核细胞计数这一假说。与年龄匹配的正常同胞（n = 22）相比，糖尿病患者（n = 27）的血液单核细胞计数显著降低（p < 0.05）。糖尿病患者血液中的乙酰乙酸（AA）和甘油三酯水平显著高于正常人。为了研究高酮血症是否能直接改变糖尿病患者的单核细胞计数，我们以人源前单核细胞系U937细胞作为体外模型，研究了酮体AA和β-羟基丁酸（BHB）对其的影响。细胞培养研究表明，AA处理U937细胞会导致剂量依赖性的生长抑制和凋亡诱导。此外，AA处理的U937细胞中谷胱甘肽（GSH）显著降低，脂质过氧化产物增加。综上所述，本研究表明酮体AA水平升高可导致单核细胞氧化损伤、加速凋亡并抑制细胞生长，进而降低I型糖尿病患者血液中的单核细胞计数。
