PDF(Pubmed)
Abstract：
BACKGROUND: Akt plays diverse roles in humans. It is involved in the pathogenesis of type 2 diabetes mellitus (T2DM), which is caused by insulin resistance. Akt also plays a vital role in human platelet activation. Furthermore, the hippocampus is closely associated with memory and learning, and a decrease in hippocampal volume is reportedly associated with an insulin-resistant phenotype in T2DM patients without dementia.
OBJECTIVE: To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM patients.
METHODS: Platelet-rich plasma (PRP) was prepared from the venous blood of patients with T2DM or age-matched controls. The pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt, p38 mitogen-activated protein (MAP) kinase and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Phosphorylation levels were quantified by densitometric analysis. Hippocampal volume was analysed using a voxel-based specific regional analysis system for Alzheimer\'s disease on magnetic resonance imaging, which proposes the Z-score as a parameter that reflects hippocampal volume.
RESULTS: The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects, whereas the levels of phosphorylated Akt corrected with GAPDH were not. However, this relationship was not observed in the control patients.
CONCLUSIONS: These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM patients. Our findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy.
OBJECTIVE: To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM patients.
METHODS: Platelet-rich plasma (PRP) was prepared from the venous blood of patients with T2DM or age-matched controls. The pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt, p38 mitogen-activated protein (MAP) kinase and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Phosphorylation levels were quantified by densitometric analysis. Hippocampal volume was analysed using a voxel-based specific regional analysis system for Alzheimer\'s disease on magnetic resonance imaging, which proposes the Z-score as a parameter that reflects hippocampal volume.
RESULTS: The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects, whereas the levels of phosphorylated Akt corrected with GAPDH were not. However, this relationship was not observed in the control patients.
CONCLUSIONS: These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM patients. Our findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy.
摘要：
背景：Akt在人类中扮演着不同的角色。它与2型糖尿病（T2DM）的发病机制有关，这是由胰岛素抵抗引起的。Akt在人血小板活化中也起着至关重要的作用。此外，海马与记忆和学习密切相关，在无痴呆的2型糖尿病患者中,海马体积减少与胰岛素抵抗表型相关.
目的：探讨2型糖尿病患者未刺激血小板Akt磷酸化与海马体积的关系。
方法：从T2DM患者或年龄匹配的对照组的静脉血中制备富血小板血浆（PRP）。将离心的PRP的沉淀裂解物进行蛋白质印迹以分析Akt的磷酸化。p38丝裂原活化蛋白(MAP)激酶和甘油醛3-磷酸脱氢酶(GAPDH)。通过光密度分析定量磷酸化水平。使用基于体素的特定区域阿尔茨海默病磁共振成像分析海马体积，它提出Z分数作为反映海马体积的参数。
结果：在T2DM受试者中，用磷酸化p38MAP激酶校正的磷酸化Akt水平与Z评分呈负相关，而用GAPDH校正的磷酸化Akt水平没有。然而,在对照组患者中未观察到这种关系.
结论：这些结果表明，T2DM患者的血小板Akt激活与海马萎缩之间可能存在负相关关系。我们的发现为T2DM海马萎缩的分子机制提供了见解。
目的：探讨2型糖尿病患者未刺激血小板Akt磷酸化与海马体积的关系。
方法：从T2DM患者或年龄匹配的对照组的静脉血中制备富血小板血浆（PRP）。将离心的PRP的沉淀裂解物进行蛋白质印迹以分析Akt的磷酸化。p38丝裂原活化蛋白(MAP)激酶和甘油醛3-磷酸脱氢酶(GAPDH)。通过光密度分析定量磷酸化水平。使用基于体素的特定区域阿尔茨海默病磁共振成像分析海马体积，它提出Z分数作为反映海马体积的参数。
结果：在T2DM受试者中，用磷酸化p38MAP激酶校正的磷酸化Akt水平与Z评分呈负相关，而用GAPDH校正的磷酸化Akt水平没有。然而,在对照组患者中未观察到这种关系.
结论：这些结果表明，T2DM患者的血小板Akt激活与海马萎缩之间可能存在负相关关系。我们的发现为T2DM海马萎缩的分子机制提供了见解。
