Tokuda Haruhiko, Hori Takamitsu, Mizutani Daisuke, Hioki Tomoyuki, Kojima Kumi, Onuma Takashi, Enomoto Yukiko, Doi Tomoaki, Matsushima-Nishiwaki Rie, Ogura Shinji, Iida Hiroki, Iwama Toru, Sakurai Takashi, Kozawa Osamu
Department of Metabolic Research, Research Institute, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan.
Department of Clinical Laboratory, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan.
World J Clin Cases. 2024 Jan 16;12(2):302-313. doi: 10.12998/wjcc.v12.i2.302.
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.
To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM patients.
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.
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.
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.
Akt在人体中发挥多种作用。它参与由胰岛素抵抗引起的2型糖尿病（T2DM）的发病机制。Akt在人类血小板激活中也起着至关重要的作用。此外，海马体与记忆和学习密切相关，据报道，在无痴呆的T2DM患者中，海马体体积减小与胰岛素抵抗表型有关。
研究未刺激血小板中Akt磷酸化与T2DM患者海马体体积之间的关系。
从T2DM患者或年龄匹配的对照者的静脉血中制备富血小板血浆（PRP）。对离心后的PRP的沉淀裂解物进行蛋白质印迹分析，以分析Akt、p38丝裂原活化蛋白（MAP）激酶和甘油醛-3-磷酸脱氢酶（GAPDH）的磷酸化情况。通过光密度分析对磷酸化水平进行定量。使用基于体素的阿尔茨海默病特定区域分析系统在磁共振成像上分析海马体体积，该系统提出Z分数作为反映海马体体积的参数。
用磷酸化p38 MAP激酶校正后的磷酸化Akt水平与T2DM受试者的Z分数呈负相关，而用GAPDH校正后的磷酸化Akt水平则不然。然而，在对照患者中未观察到这种关系。
这些结果表明，T2DM患者血小板Akt激活与海马体萎缩之间可能存在负相关关系。我们的研究结果为T2DM海马体萎缩的分子机制提供了见解。
