Evaluation of Muscle microRNA Expression in Relation to Human Peripheral Insulin Sensitivity: A Cross-Sectional Study in Metabolically Distinct Subject Groups
Dennis Dahlmans, Alexandre Houzelle, Johanna A. Jörgensen, Esther Phielix, Lucas Lindeboom, Matthijs K. C. Hesselink, Patrick Schrauwen, Joris Hoeks
Abstract
In recent years, several microRNAs (miRNAs)-post-transcriptional regulators of gene expression-have been linked to the regulation of peripheral insulin sensitivity. Many of these studies, however, have been conducted in cell or animal models and the few human studies available lack adequate measurements of peripheral insulin sensitivity. In the present study, we examined the expression of 25 miRNAs, putatively involved in (peripheral) insulin sensitivity, in skeletal muscle biopsies from extensively phenotyped human individuals, widely ranging in insulin sensitivity. To identify miRNAs expressed in skeletal muscle and associated with insulin sensitivity and type 2 diabetes, a comprehensive PubMed-based literature search was performed. Subsequently, the expression of selected miRNAs was determined by RT-qPCR using predesigned 384-well Pick-&-Mix miRNA PCR Panel plates in muscle biopsies from type 2 diabetes patients, non-diabetic obese/overweight individuals, lean sedentary individuals and endurance-trained athletes. In all subjects, peripheral insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. The literature search resulted in 25 candidate miRNAs, 6 of which were differentially expressed in human type 2 diabetes compared to non-diabetic obese/overweight individuals. In turn, four of these miRNAs, i.e., miRNA27a-3p (r = -0.45, p = 0.0012), miRNA-29a-3p (r = -0.40, p = 0.0052), miRNA-29b-3p (r = -0.70, p < 0.0001) and miRNA-29c-3p (r = -0.50, p = 0.0004) demonstrated strong negative correlations with peripheral insulin sensitivity across all four subject groups. We identified miR-27a-3p and all members of the miRNA-29 family as potential regulatory players in insulin sensitivity in humans. These miRNA's may represent interesting novel targets for maintaining or improving insulin sensitivity.
Pharmacology, Toxicology and Pharmaceutical Science
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Other
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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 January 2022.
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#5,707,816
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Outputs from Frontiers in Physiology
#2,620
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#90,012
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Outputs of similar age from Frontiers in Physiology
#67
of 300 outputs
Altmetric has tracked 22,994,508 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 13,752 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one has done well, scoring higher than 80% of its peers.
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