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Effect of Glycated Albumin in the expression of glucose transporter GLUT4 in adipose cell: potencial participation of transcription factor NFKB

Grant number: 16/17002-4
Support type:Scholarships in Brazil - Master
Effective date (Start): December 01, 2016
Effective date (End): July 31, 2018
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Ubiratan Fabres Machado
Grantee:Maria Luiza Estimo Michalani
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Diabetes mellitus (DM) is a chronic disease characterized by the loss of glycemic homeostasis. With the progression of the disease, there is an establishment of a chronic hyperglycemia condition, which results in accelerated formation of advanced glycated end products (AGEs), that may compromise the uptake glucose ability by muscle and adipose tissues, contributing to the loss of glycemic homeostasis.The interaction between the RAGE receptor with AGE generates an oxidative stress capable of activates the NFKB pathway, a transcriptional factor that can either stimulate gene transcriptional (for example, Ager and Nfkb1 genes) or inhibit the gene transcriptional (for example, Slc2a4 gene). The Slc2a4 gene expressed in musle and adipose cells and it encodes the GLUT4 transporter, which is translocated to the plasma membrane, under stimulation of insulin, increasing glucose uptake, and, thereby regulating glycemic homeostasis.Although AGEs are studied in the pathogenesis of diabetes complication, little or nothing is known about its potential contribution to the impairment of glucose uptake by muscle and adipose tissue characteristic of the diabetes state. Preliminary studies by our group have shown that treatment with glycated albumin of normal rats reduces sensibility of insulin. However, it was not shown whether this effect involves a direct action of AGEs on the expression of Slc2a4 gene.This project, thus, proposes to analyze the effects of glycated albumin on the expression of Slc2a4 gene and protein GLUT4 in 3T3-L1 adipocytes lineage and verify whether this effect is mediated by the activation of NFKB pathway.