Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

作者：Rahimi Mehran; Vinciguerra Manlio; Daghighi Mojtaba; Oezcan Behiye; Akbarkhanzadeh Vishtaseb; Sheedfar Fareeba; Amini Marzyeh; Mazza Tommaso; Pazienza Valerio; Motazacker Mahdi M; Mahmoudi Morteza; De Rooij Felix W M; Sijbrands Eric; Peppelenbosch Maikel P; Rezaee Farhad^*

来源：Oncotarget, 2015, 6(30): 29818-29832.

DOI：10.18632/oncotarget.4904

• aging
• obesity
• diabetes
• age-related diabetes neuropathy
• pancreas

Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy.
AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1-Obese and 2-Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3-Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling).
Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs.

• 出版日期2015-10-6