Age-Related Obesity and Type 2 Diabetes Dysregulate Neuronal Associated Genes and Proteins in Humans Publisher Pubmed



Rahimi M¹ ; Vinciguerra M^{2, 3} ; Daghighi M⁴ ; Ozcan B⁵ ; Akbarkhanzadeh V⁶ ; Sheedfar F⁷ ; Amini M⁸ ; Mazza T⁹ ; Pazienza V³ ; Motazacker MM¹⁰ ; Mahmoudi M^{11, 12} ; De Rooij FWM¹³ ; Sijbrands E¹³ ; Peppelenbosch MP¹⁴ Show All Authors
Source: Oncotarget Published:2015

Abstract

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.