Effect of miR-696 e miR-let7b on the mitochondrial function in insulin resistant muscle cells

• Grant number: 16/04791-0
• Support type: Research Grants - Visiting Researcher Grant - International
• Duration: June 12, 2016 - June 17, 2016
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Leonardo dos Reis Silveira
• Grantee: Leonardo dos Reis Silveira
• Visiting researcher: Richard C. Scarpulla
• Visiting researcher institution: Northwestern University, Evanston, United States
• Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 15/12611-0 - Molecular mechanisms involved in pancreatic beta cell disfunction and dead in diabetes mellitus: strategies for the inhibition of these processes and restoration of the insular mass, AP.TEM

Abstract

Insulin resistance is a feature associate with type II diabetes but its mechanism is not fully understood. Recently, micro-RNAs (miRNAs) have been described as non-coding molecules associated with post-transcriptional gene regulation and, therefore, regulate several physiological and pathological processes like growth, differentiation, metabolism, cancer and diabetes. It is known that the miR-696 regulates Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1±), involved in mitochondrial biogenesis. Our previous study shown that in diabetic rats, the miRNA let-7b regulates the protein Akt1. Thus, we suggested that these miRNAs may be involved at insulin resistance of skeletal muscle cells. In fact, we have also observed a marked expression of miR-696 and miR-let7b in insulin resistant muscle cells. In contrast, inhibition of miR-696 and miR-let7b expression through antagomir lead to an increased mitochondrial oxygen consumption. This effect was reflected in improved insulin response. We are proposing, therefore, that reduction of miR-696 and miR-let7b expression might exert an important role on the muscle mitochondrial function indicating that miR-696 and miR-let7b might be important therapeutic target to the control of muscle insulin resistance and obesity. If our hypothesis is true, the overexpression of miR-696 in a trangenic mouse will lead to a reduced PGC1± expression and impairing the muscle mitochondrial biogenesis. (AU)