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Effect of advanced glycated albumin upon Slc2a4 gene in skeletal muscle

Grant number: 12/15514-7
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2012
Effective date (End): June 30, 2016
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Ubiratan Fabres Machado
Grantee:Danilo Antônio Corrêa Pinto Júnior
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:12/04831-1 - New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives, AP.TEM

Abstract

Nowadays, diabetes affects a lot of people in worldwide. In healthy people there is a balance between insulin secretion and glucose uptake; however, that is disrupted in diabetic state. Skeletal muscle, 40% of body mass, is an important territory of glucose uptake, so it contributes fundamentally to glicemic homeostasis. The glucose uptake increases in response to insulin and muscle contraction, process whereby GLUT4 (encoded by Slc2a4 gene) plays a fundamental role. In diabetic, GLUT4 expression is decreased, attenuating glucose uptake over any situation. Our group had demonstrated in incubated muscle in vitro, that insulin and muscle contraction increase quickly Slc2a4/GLUT4 expression; however the same result does not occur in muscle from diabetic rats. It is known that in diabetes, because of hyperglycemia, advanced glycation ends (AGEs) products are generated, which are recognized by cellular receptors, triggering intracellular signals that activate NF-ºB, a supposed inhibitor of Slc2a4 gene. Literature shows that adipocytes that were incubated with advanced glycation modified albumin decreases GLUT4 expression; however, nothing is known about AGEs effect on Slc2a4/GLUT4 expression in the skeletal muscle in response to both insulin and muscle contraction, in diabetic or not rats. This project aims to investigate in skeletal muscle of diabetic and non-diabetic rats, the in vitro effect of advanced glycation modified albumin upon Slc2a4/GLUT4 expression in skeletal muscle and glucose uptake stimulated by insulin or muscular contraction.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ESTEVES, V, JOAO; YONAMINE, CAIO Y.; PINTO-JUNIOR, DANILO C.; GERLINGER-ROMERO, FREDERICO; ENGUITA, FRANCISCO J.; MACHADO, UBIRATAN F.. Diabetes Modulates MicroRNAs 29b-3p, 29c-3p, 199a-5p and 532-3p Expression in Muscle: Possible Role in GLUT4 and HK2 Repression. FRONTIERS IN ENDOCRINOLOGY, v. 9, . (16/15603-0, 12/20432-0, 12/15514-7, 17/19449-9)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
PINTO JÚNIOR, Danilo Antônio Corrêa. Effect of albumin modified by advanced glycation in gene expression of SLC2A4 in skeletal muscle.. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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