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Role of Previuos resistance exercise training on renal and muscle mTOR signaling in rats with diabetes

Grant number: 11/20109-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2012
Effective date (End): December 31, 2014
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Nestor Schor
Grantee:Kleiton Augusto dos Santos Silva
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated scholarship(s):12/03142-8 - Mechanisms and mediators that are associated with catabolic conditions to impair satellite cell function: role of glucocorticoids, BE.EP.DR

Abstract

BACKGROUND: Molecule mammalian target of rapamycin (mTOR) is responsible for cell growth and proliferation. Diabetes mellitus (DM) may cause glomerular hypertrophy and muscle atrophy despite inhibition of this pathway in muscle tissue and activation in renal tissue, a fact that has stimulated this work. On the other hand, resistance exercise training also known as strength training or weight training, appears as an alternative therapy associated with the treatment of chronic degenerative diseases such as DM, playing an important role in promoting the health of patients with this disease, however, little is known about the early intervention of this type of training and what is its relationship with the mTOR pathway. OBJECTIVE: To evaluate the resistance physical training prior to modulate the mTOR signaling pathway in skeletal muscle and kidney in rats with experimental DM. MATERIAL AND METHODS: Wistar rats will be weighing between 150 - 180g, with food and water ad libitum. The animals will be divided into five groups: control (C), diabetic (D), trained diabetic (DT), trained control (TC) and trained diabetic prior (DTP). Physical training will consist of performing resisted by animals climbing on a device especially designed for this purpose. Animals will hold up to 8 climbs, with an interval of 1 minute of rest between ascents, supporting a workload to be scaled by 50 to 80% of the capacity test conducted every two weeks and will be adapted to each animal the progression of training. All animals will be followed for 13 weeks, and the length of training will be 8 weeks for groups CT, DT and DTP. For the DTP group, will hold an additional 4 weeks of training prior to the establishment of DM mimicking the occurrence of this disease in an animal "trained" (physically active). Thus, all animals will be monitored for 13 weeks, for the systematization of the protocol. Renal function is assessed by collecting blood and urine of 24 h, where we will make analysis of creatinine, urea, Na +, K +, and proteinuria. The kidney tissue and skeletal muscle (EDL - Extender Digitoruim Long, plant and soleus) will be collected for analysis of gene expression and protein. Assessed by RT-PCR and Western blot, p-Akt, p-mTOR, p70S6K and 4E-BP1. These molecules participate in the pathway responsible for cell growth and are important in signaling of glomerular hypertrophy and muscle. In addition, we analyze the level of muscle atrophy as promoted by the expression of DM-1 Atrogin of MuRF1, the p-FOXO and FOXO. It is known that Atrogin-1 and MuRF1 are E3 ligases usually expressed in the ubiquitin-proteasome.