Type 2 diabetes mellitus (T2DM) represents a major health problem due to the development of insulin resistance, and microRNAs (miRNA or miR) molecules were recently pointed as gene regulators of metabolic pathways. The aim of this project is to: 1) investigate in the skeletal muscle of C57BL/6 mice lineage, if miRs-1, 133, 206, 208b and 499 (specific for muscle) and miR-223 (non-specific) regulate genes involved in insulin resistance induced by high fat diet, and 2) if these miRNAs may be related to the development of insulin resistance or are therapeutic targets of drugs that improve that resistance. Mice of the C57BL / 6 lineage will be fed with a balanced or hyperlipidic diet for 8 weeks. In the last two weeks of diet prior to sacrifice of a group of animals in each diet type, fenofibrate will be administrated. The following parameters will be evaluated: insulin sensitivity; determinations of plasma parameters such as total cholesterol and fractions, triglycerides, liver enzymes, glucose and insulin, insulin responsiveness in muscle incubated; analysis and identification of miRNAs in samples of skeletal muscle with and without treatment with the drug fenofibrate, mRNA expression target genes of identified miRNAs and miRNA functional analysis. A better knowledge of microRNAs mechanisms of action in skeletal muscle will assist in understanding the progression of insulin resistance and T2DM, and the development of new therapies that target miRNAs in this tissue.
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