Increased Fructose 2,6-bisphosphate in peripheral blood mononuclear cells of patients with diabetes.

Increased Fructose 2,6-bisphosphate in peripheral blood mononuclear cells of patients with diabetes.
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DOI:
10.1507/endocrj.k06-205
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发表时间:
2007-08
期刊:
影响因子:
2
通讯作者:
T. Atsumi;H. Chiba;N. Yoshioka;R. Bucala;T. Koike
T. Atsumi;H. Chiba;N. Yoshioka;R. Bucala;T. Koike
中科院分区:
医学4区
文献类型:
--
作者:
T. Atsumi;H. Chiba;N. Yoshioka;R. Bucala;T. Koike

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2,6-二磷酸果糖(F2,6BP)是糖酵解的限速酶6-磷酸果糖-1-激酶的一种强有力的变构激活剂。淋巴细胞的有丝分裂刺激与葡萄糖利用率的提高和F2,6BP介导的糖酵解激活有关。为了确定高血糖对淋巴细胞胞内糖酵解的影响,我们测定了糖尿病患者和正常人外周血单个核细胞内F2,6BP的含量。共有62名受试者参与了本研究。采集静脉血,用Ficoll梯度分离法分离外周血单核细胞。正常人外周血单个核细胞内F2,6BP水平显著低于年龄匹配的糖尿病患者。我们观察到细胞内F2,6BP水平与HbA1c评估的长期血糖控制之间存在显著的正相关。这些数据表明,高血糖会增加免疫细胞内的F2,6BP。这些发现可能有助于阐明糖尿病患者免疫细胞功能受损的原因。
Fructose 2,6-bisphosphate (F2,6BP) is a powerful allosteric activator of 6-phosphofructo-1-kinase, which is the rate-limiting enzyme for glycolysis. Mitogenic stimulation of lymphocytes is related to an enhanced rate of glucose utilization and F2,6BP mediated activation of glycolysis. To determine the effect of hyperglycemia on intracellular glycolysis of lymphocytes, we measured intracellular F2,6BP content in peripheral blood mononuclear cells obtained from patients with diabetes and normal subjects. A total of 62 subjects participated in the present study. Venous blood samples were collected and peripheral blood mononuclear cells were separated by Ficoll gradients. Intracellular F2,6BP levels in peripheral blood mononuclear cells from normal control subjects were significantly lower than age-matched diabetic subjects. We observed a significant positive correlation between intracellular F2,6BP levels and long term glycemic control, as assessed by HbA1c. These data suggest that hyperglycemia increases intracellular F2,6BP in immune cells. These findings may help to clarify the impaired function in immune cells in patients with diabetes.