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Role of microRNAs in the development of insulin resistance


A clinically relevant question is whether microRNA (miR or miRNA) levels are capable of assessing the probability of diabetes mellitus type 2 (DM2) manifestations in patients with insulin resistance. The aim of this study is to investigate which microRNAs regulate the genes involved with insulin resistance after high fat diet and whether miRNAs could be biomarkers for DM2 manifestation and/or progression. Male C57BL/6 mice will receive a balanced or high-fat diet during 4, 8 or 12 weeks (weeks 0 to 12). In the week 10, a group of mice will continue receiving balanced or high-fat diet supplemented with ezetimibe, fenofibrate or rosiglitazone. At the end of the treatment, the following assessments will be performed: insulin sensitivity; plasma parameters determinations, such as total cholesterol and fractions, triglycerides, hepatic and enzymes, glucose and insulin; analyses and identification of miRNAs in plasma, liver, adipocyte and skeletal muscle; mRNA expression of identified miRNA target genes and functional analysis of miRNAs. A better understanding of the mechanisms involved in miRNAs liberation in circulation and in their regulation of genes associated with insulin resistance will have impact on the elucidation of the issues related to diabetes progression, as well as the development of new therapies that targets miRNAs for therapeutic intervention. (AU)

Scientific publications (5)
(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)
DE MENDONCA, MARIANA; DE SOUSA, ERICA; DA PAIXAO, AILMA O.; DOS SANTOS, BRUNA ARAUJO; SPAGNOL, ALEXANDRE ROVERATTI; MURATA, GILSON M.; ARAUJO, HYGOR N.; DE LIMA, TANES IMAMURA; PASSOS SIMOES FROES GUIMARAES, DIMITRIUS SANTIAGO; SILVEIRA, LEONARDO R.; RODRIGUES, ALICE C. MicroRNA miR-222 mediates pioglitazone beneficial effects on skeletal muscle of diet-induced obese mice. Molecular and Cellular Endocrinology, v. 501, FEB 5 2020. Web of Science Citations: 0.
FRIAS, FLAVIA DE T.; ROCHA, KARINA C. E.; DE MENDONCA, MARIANA; MURATA, GILSON M.; ARAUJO, HYGOR N.; DE SOUSA, LUIS G. O.; DE SOUSA, ERICA; HIRABARA, SANDRO M.; LEITE, NAYARA DE C.; CARNEIRO, EVERARDO M.; CURI, RUI; SILVEIRA, LEONARDO R.; RODRIGUES, ALICE C. Fenofibrate reverses changes induced by high-fat diet on metabolism in mice muscle and visceral adipocytes. Journal of Cellular Physiology, v. 233, n. 4, p. 3515-3528, APR 2018. Web of Science Citations: 4.
RODRIGUES, ALICE C.; NERI, ELIDA ADALGISA; VERISSIMO-FILHO, SIDNEY; REBOUCAS, NANCY AMARAL; HIRATA, ROSARIO D. C.; YU, AI-MING. Atorvastatin attenuation of ABCB1 expression is mediated by microRNA miR-491-3p in Caco-2 cells. European Journal of Pharmaceutical Sciences, v. 93, p. 431-436, OCT 10 2016. Web of Science Citations: 5.
FRIAS, FLAVIA DE TOLEDO; DE MENDONCA, MARIANA; MARTINS, AMANDA ROQUE; GINDRO, ANA FLAVIA; COGLIATI, BRUNO; CURI, RUI; RODRIGUES, ALICE CRISTINA. Myomirs as Markers of insulin resistance and Decreased Myogenesis in skeletal Muscle of Diet-induced Obese Mice. FRONTIERS IN ENDOCRINOLOGY, v. 7, JUN 27 2016. Web of Science Citations: 6.
HIRABARA, SANDRO M.; GORJAO, RENATA; VINOLO, MARCO A.; RODRIGUES, ALICE C.; NACHBAR, RENATO T.; CURI, RUI. Molecular Targets Related to Inflammation and Insulin Resistance and Potential Interventions. JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2012. Web of Science Citations: 48.

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