Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada.
Neurobiol Aging. 2010 Sep;31(9):1503-15. doi: 10.1016/j.neurobiolaging.2008.08.019. Epub 2008 Oct 23.
Strong epidemiologic evidence suggests an association between Alzheimer disease (AD) and type 2 diabetes. To determine if amyloid beta (Abeta) 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 Abeta, hyperphosphorylated tau, ubiquitin, apolipoprotein E, apolipoprotein(a), IB1/JIP-1 and JNK1 were detected in Langerhans islets in type 2 diabetic patients. Abeta 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 Abeta 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 Abeta deposits and hyperphosphorylated tau may also occur in other organs than the brain.
强有力的流行病学证据表明阿尔茨海默病（AD）与 2 型糖尿病之间存在关联。为了确定 2 型糖尿病中是否存在β淀粉样蛋白（Abeta）和过度磷酸化的 tau，分析了 21 例尸检病例的胰腺组织（10 例 2 型糖尿病和 11 例对照）。通过 RT-PCR 在人胰腺和培养的胰岛素瘤β细胞（INS-1）中鉴定出 APP 和 tau mRNA。通过 Western 印迹在胰腺提取物中检测到明显的 APP 和 tau 带。在 2 型糖尿病患者的胰岛中检测到聚集的 Abeta、过度磷酸化的 tau、泛素、载脂蛋白 E、载脂蛋白（a）、IB1/JIP-1 和 JNK1。Abeta 与胰岛淀粉样沉积中的胰淀素共定位。通过红外微光谱（SIRMS）显示胰岛淀粉样沉积物中的β片层形成。LPS 还增加了非神经元细胞中的 APP。我们得出结论，Abeta 沉积和过度磷酸化的 tau 也与 2 型糖尿病有关，突出了神经退行性疾病（包括 AD 和 2 型糖尿病）中的共同发病特征，并表明 Abeta 沉积和过度磷酸化的 tau 也可能发生在大脑以外的其他器官中。
