The microRNA signature in response to insulin reveals its implication in the transcriptional action of insulin in human skeletal muscle and the role of a sterol regulatory element-binding protein-1c/myocyte enhancer factor 2C pathway.

OBJECTIVE: Factors governing microRNA expressions in response to changes of cellular environment are still largely unknown. Our aim was to determine whether insulin, the major hormone controlling whole-body energy homeostasis, is involved in the regulation of microRNA expressions in human skeletal muscle. RESEARCH DESIGN AND METHODS: We carried out comparative microRNA (miRNA) expression profiles in human skeletal muscle biopsies before and after a 3-h euglycemic-hyperinsulinemic clamp, with TaqMan low-density arrays. Then, using DNA microarrays, we determined the response to insulin of the miRNA putative target genes in order to determine their role in the transcriptional action of insulin. We further characterized the mechanism of action of insulin on two representative miRNAs, miR-1 and miR-133a, in human muscle cells. RESULTS: Insulin downregulated the expressions of 39 distinct miRNAs in human skeletal muscle. Their potential target mRNAs coded for proteins that were mainly involved in insulin signaling and ubiquitination-mediated proteolysis. Bioinformatic analysis suggested that combinations of different downregulated miRNAs worked in concert to regulate gene expressions in response to insulin. We further demonstrated that sterol regulatory element-binding protein (SREBP)-1c and myocyte enhancer factor 2C were involved in the effect of insulin on miR-1 and miR-133a expression. Interestingly, we found an impaired regulation of miRNAs by insulin in the skeletal muscle of type 2 diabetic patients, likely as consequences of altered SREBP-1c activation. CONCLUSIONS: This work demonstrates a new role of insulin in the regulation of miRNAs in human skeletal muscle and suggests a possible implication of these new modulators in insulin resistance.

Blood pressure and heart rate variability changes during cardiac surgery with cardiopulmonary bypass.

This study investigated patients undergoing elective cardiac surgery to evaluate the effects of cardiopulmonary bypass (CPB) on the spontaneous variability of mean arterial pressure (MAP) and heart rate (HR). Forty-one adult patients receiving different cardiovascular system drugs were included in the study. Patients were divided into three groups: no preoperative pharmacological cardiovascular treatment (n = 12), beta-blocker (BB) (n = 13), and angiotensin-converting enzyme inhibition (ACEI) (n = 16). MAP was recorded before anaesthesia until the end of surgery. MAP and HR variability was analysed in very low- (VLF), low- (LF) and high-frequency bands. The LF spectral component of MAP was observed to decrease in patients under ACEI (-92%) or BB (-87%) following induction of anaesthesia. In addition, during CPB, VLF power decreased in BB group (-67%), and LF power decreased in ACEI group (-77%). Concerning HR, VLF spectral power decreased following anaesthesia in BB group (-74%). In addition, after CPB, VLF power reached lower value in ACEI group than in BB group (P < 0.05). LF spectral power of HR showed a large decrease after CPB in ACEI group (-89%). This study showed that MAP variability did not change during CPB in patients with no preoperative pharmacological cardiovascular treatment, suggesting an unaltered vascular control of MAP. Moreover, the change in LF spectral power of MAP in ACEI and BB groups, suggests that both the renin-angiotensin and sympathetic systems participate to the genesis of LF variability of MAP.