Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes.

Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes.
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DOI:
10.1016/j.neurobiolaging.2008.08.019
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发表时间:
2010-09
影响因子:
4.2
通讯作者:
McGeer, Patrick L.
McGeer, Patrick L.
中科院分区:
医学2区
文献类型:
--
作者:
Miklossy, Judith;Qing, Hong;Radenovic, Aleksandra;Kis, Andras;Vileno, Bertrand;Laszlo, Forro;Miller, Lisa;Martins, Ralph N.;Waeber, Gerard;Mooser, Vincent;Bosman, Fred;Khalili, Kamel;Darbinian, Nune;McGeer, Patrick L.

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强有力的流行病学证据表明阿尔茨海默病(AD)和2型糖尿病之间存在关联。为了确定淀粉样蛋白β(A β)和过度磷酸化tau蛋白是否发生在2型糖尿病中,分析了21例尸检病例(10例2型糖尿病和11例对照)的胰腺组织。通过RT-PCR在人胰腺和培养的胰岛素瘤β细胞(INS-1)中鉴定APP和tau mRNA。在胰腺提取物中通过Western印迹检测到突出的APP和tau条带。2型糖尿病患者胰岛中检测到聚集的A β、过度磷酸化的tau蛋白、泛素、载脂蛋白E、载脂蛋白(a)、IB1/JIP-1和JNK1。胰岛淀粉样沉积物中A β与胰淀素共定位。原位β折叠形成胰岛淀粉样蛋白沉积物显示红外显微光谱(SIRMS)。LPS也增加非神经元细胞中的APP。我们得出结论,A β沉积和过度磷酸化tau蛋白也与2型糖尿病相关,突出了神经退行性疾病(包括AD和2型糖尿病)的常见发病特征,并表明A β沉积和过度磷酸化tau蛋白也可能发生在大脑以外的其他器官中。
Strong epidemiologic evidence suggests an association between Alzheimer disease (AD) and type 2 diabetes. To determine if amyloid beta (Aβ) and hyperphosphorylated tau occurs in type 2 diabetes, pancreas tissues from 21 autopsy cases (10 type 2 diabetes and 11 controls) were analyzed. APP and tau mRNAs were identified in human pancreas and in cultured insulinoma beta cells (INS-1) by RT-PCR. Prominent APP and tau bands were detected by Western blotting in pancreatic extracts. Aggregated Aβ, hyperphosphorylated tau, ubiquitin, apolipoprotein E, apolipoprotein(a), IB1/JIP-1 and JNK1 were detected in Langerhans islets in type 2 diabetic patients. Aβ was co-localized with amylin in islet amyloid deposits. In situ beta sheet formation of islet amyloid deposits was shown by infrared microspectroscopy (SIRMS). LPS increased APP in non-neuronal cells as well. We conclude that Aβ deposits and hyperphosphorylated tau are also associated with type 2 diabetes, highlighting common pathogenetic features in neurodegenerative disorders, including AD and type 2 diabetes and suggesting that Aβ deposits and hyperphosphorylated tau may also occur in other organs than the brain.
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