Effects of endurance and strength exercises on the glucose uptake pathways in knockout heterozygous GLUT4 mice

• Grant number: 13/20293-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2014
• End date: October 23, 2018
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: José Rodrigo Pauli
• Grantee: José Diego Botezelli
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated scholarship(s): 16/23251-7 - The role of hyperinsulinemia on SIRT activity, PPAr-y acetylation and UCP expression in adipose tissue., BE.EP.PD

Abstract

A few metabolic parameters require adjustment accurate and rigid as glycemic control. Changes in blood glucose trigger several systemic changes in the body and the malfunction of this regulation may lead to the appearance of a large spectrum of disorders in metabolism that grouped are called Metabolic Syndrome. Thus, it is important to unfold the mechanisms by which glucose homeostasis is regulated and, what the main molecules involved in this control. A well-known agent that generates substantially significant responses in the regulation of glucose uptake is the physical exercise. This energy imbalance triggers the activation of many mechanisms increasing glucose transport blood to the intracellular environment through the glucose transporters. However, these adjustments have not yet been fully described in the literature. For this, the main purpose of this study is to compare the impact of different exercise protocols in glucose uptake independent (exercise control) and insulin dependent (molecular control) pathways. We will use control mice (GLUT+/+) and genetically engineered GLUT4+/- 120 days old. These animals will be separated into four distinct groups (GLUT4+ /+ Sedentary, GLUT4+/- Sedentary, GLUT4+/- Endurance, GLUT4+/- Strength). During and in the end of the experiment, we will analyze some the adaptations resulted from exercise: glucose tolerance , insulin sensitivity , biochemical parameters ( glucose , cholesterol , and triglycerides , proteins involved in the synthesis of GLUT4 ( MEF and GEF ), glucose uptake regulated by muscle contraction and energy imbalance ( AMPK , CaMKII ) and by insulin action on in the muscle ( IR / PIR ; IRS-1/pIRS-1 ; PI3K/pPI3K , Akt / pAkt ) and adipose tissue ( IR / PIR ; IRS-2/pIRS- 2 PI3K/pPI3K , Akt / pAkt ) and finally the presence of GLUT4 membrane. The analyzes will be performed using molecular biology techniques such as western blotting, immunofluorescence and qPCR. At the end of the experiment, we expect to elucidate the differences between these two major kind of exercise in the synthesis and translocation of GLUT4 , thereby providing new therapeutic possibilities and treatment for disorders evolving the metabolic syndrome.

Scientific publications

(6)

(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)

GASPAR, RAFAEL CALAIS; KUGA, GABRIEL KEINE; MUNOZ, VITOR ROSETTO; COOPE, ANDRESSA; CAMBRI, LUCIELI TERESA; GHEZZI, ANA CAROLINA; DE MOURA, LEANDRO PEREIRA; CURIACOS DE ALMEIDA LEME, JOSE ALEXANDRE; PAULI, JOSE RODRIGO; BOTEZELLI, JOSE DIEGO. PHYSICAL TRAINING PREVENT AND TREAT HEPATIC LIPID ACCUMULATION INDUCED BY FRUCTOSE-RICH DIET. BIOSCIENCE JOURNAL, v. 34, n. 4, p. 1041-1050, JUL-AUG 2018. (13/20293-2)

GASPAR, RAFAEL CALAIS; BOTEZELLI, JOSE DIEGO; KUGA, GABRIEL KEINE; MUNOZ, VITOR ROSETTO; COOPE, ANDRESSA; PEREIRA, RODRIGO MARTINS; RAMOS DA SILVA, ADELINO SANCHEZ; CINTRA, DENNYS ESPER; DE MOURA, LEANDRO PEREIRA; ROPELLE, EDUARDO ROCHETE; et al. High Dosage of Vitamin D Regulates the Energy Metabolism and Increases Insulin Sensitivity, but are Associated with High Levels of Kidney Damage. Drug Development Research, v. 78, n. 5, p. 203-209, AUG 2017. (16/18488-8, 13/20293-2)

GASPAR, RAFAEL CALAIS; KUGA, GABRIEL KEINE; MUNOZ, VITOR ROSETTO; COOPE, ANDRESSA; CAMBRI, LUCIELI TERESA; GHEZZI, ANA CAROLINA; DE MOURA, LEANDRO PEREIRA; CURIACOS DE ALMEIDA LEME, JOSE ALEXANDRE; PAULI, JOSE RODRIGO; BOTEZELLI, JOSE DIEGO. PHYSICAL TRAINING PREVENT AND TREAT HEPATIC LIPID ACCUMULATION INDUCED BY FRUCTOSE-RICH DIET. BIOSCIENCE JOURNAL, v. 34, n. 4, p. 10-pg., 2018-07-01. (13/20293-2)

BOTEZELLI, JOSE D.; COOPE, ANDRESSA; GHEZZI, ANA C.; CAMBRI, LUCIELI T.; MOURA, LEANDRO P.; SCARIOT, PEDRO P. M.; GASPAR, RODRIGO STELLZER; MEKARY, RANIA A.; ROPELLE, EDUARDO ROCHETE; PAULI, JOSE RODRIGO. Strength Training Prevents Hyperinsulinemia, Insulin Resistance, and Inflammation Independent of Weight Loss in Fructose-Fed Animals. SCIENTIFIC REPORTS, v. 6, AUG 4 2016. (13/21491-2, 13/20293-2, 16/14380-8)

CAMBRI, LUCIELI T.; RIBEIRO, CARLA; BOTEZELLI, JOSE D.; GHEZZI, ANA C.; MELLO, MARIA A. R.. Muscle glycogen metabolism changes in rats fed early postnatal a fructose-rich diet after maternal protein malnutrition: effects of acute physical exercise at the maximal lactate steady-state intensity. DIABETOLOGY & METABOLIC SYNDROME, v. 6, NOV 6 2014. (13/20293-2)

LENHARE, LUCIENE; SILVA, VAGNER R.; KATASHIMA, CARLOS K.; MICHELETTI, THAYANA O.; BOTEZELLI, JOSE DIEGO; GASPAR, RAFAEL C.; GASPAR, RODRIGO S.; MUNOZ, VITOR R.; MARINHO, RODOLFO; MOURA, LEANDRO P.; et al. Chronic Exercise Reduces The Sirt1 S-nitrosation In The Liver Of Old Mice. MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, v. 48, n. 5, p. 1-pg., 2016-05-01. (13/20293-2)