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

型糖尿病患者胰腺中的 β 淀粉样蛋白和过度磷酸化的 tau 沉积

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作者:Judith Miklossy, Hong Qing, Aleksandra Radenovic, Andras Kis, Bertrand Vileno, Forró Làszló, Lisa Miller, Ralph N Martins, Gerard Waeber, Vincent Mooser, Fred Bosman, Kamel Khalili, Nune Darbinian, Patrick L McGeer

Abstract

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.

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