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Abstract：
Increased apoptotic lymphocytes have been correlated to a high incidence of infection in poorly controlled diabetes. This study aimed to determine whether altered voltage-dependent anion channel (VDAC)-hexokinase (HK) association contributes to the increase in apoptosis. Mouse peripheral blood lymphocytes (PBL) exposed to high glucose (Glc)/palmitic acid (PA) were used as the in vitro model, which was compared with PBL isolated from alloxan-induced diabetic mice (in vivo model). Our results showed a significant increase in apoptosis as indicated by the apoptotic index, caspase-3 activity, mitochondrial membrane potential and ultrastructural study. HK and glucose-6-phosphate dehydrogenase (G6PDH) activities were markedly reduced with a profound increase in glucose-6-phosphate level. Co-immunoprecipitation confirms HK interaction with VDAC, an outer mitochondrial membrane protein. Inhibited glycolytic enzyme, i.e. HK and reduced HK-VDAC interaction in our study could contribute to increased apoptosis in lymphocytes exposed to high Glc/PA. Targeting HK-VDAC interaction may therefore provide therapeutic potential for the treatment of diabetes-associated infection.
摘要：
在控制不佳的糖尿病中，凋亡淋巴细胞的增加与感染的高发生率相关。这项研究旨在确定电压依赖性阴离子通道（VDAC）-己糖激酶（HK）缔合的改变是否有助于细胞凋亡的增加。小鼠外周血淋巴细胞（PBL）暴露于高糖（Glc）/棕榈酸（PA）作为体外模型，将其与从四氧嘧啶诱导的糖尿病小鼠（体内模型）分离的PBL进行比较。我们的结果显示细胞凋亡显著增加，如凋亡指数所示，caspase-3活性，线粒体膜电位和超微结构研究。HK和葡萄糖-6-磷酸脱氢酶（G6PDH）活性显着降低，葡萄糖-6-磷酸水平显着增加。免疫共沉淀证实了HK与VDAC的相互作用，线粒体外膜蛋白.抑制糖酵解酶，即在我们的研究中HK和减少的HK-VDAC相互作用可能有助于暴露于高Glc/PA的淋巴细胞中的凋亡增加。因此,靶向HK-VDAC相互作用可以为糖尿病相关感染的治疗提供治疗潜力。
