The role of circulating miRNA-29a in exercise training-induced improvements in insulin sensitivity

A family history of Type 2 Diabetes (FH) is considered a risk factor for development of type 2 diabetes (T2D). Exercise training is a powerful preventive strategy for this disease progression. Circulating micro‐RNAs (miRNAs) are a novel class of signaling molecules that have recently been linked to regulation of insulin sensitivity (IS) and various physiological responses to exercise. Elevated miRNA‐29a expression has been reported in serum and skeletal muscle of T2D patients. However, the effects of exercise training on miRNA‐29a are not known. The purpose of this study was to examine the effects of eight weeks of combined endurance and resistance exercise training on miRNA‐29a expression in healthy Mexican‐American men with/without a FH . Methods 16 sedentary, normoglycemic men (mean ± SEM; age: 23.3 ± 0.6; BMI: 26.9 ± 0.9) with/without a family history of T2D (FH‐/FH+) underwent eight weeks (3x/wk) of combined exercise training. A five‐day standardized diet was provided prior to test days. After an overnight fast, subjects reported for IS assessment via the gold‐standard hyperinsulinemic euglycemic clamp technique and collection of serum for miRNA detection. Total RNA was extracted and reverse transcribed to cDNA followed by measurement of miRNA‐29a expression performed via qRT‐PCR. Differences between groups at baseline were analyzed by independent t‐tests. Group and time effects of the exercise training intervention were analyzed by two‐way ANOVA. Relationships between miRNA‐29 expression and IS were determined using Pearson correlation analysis. Results While fasting blood glucose (FBG) and IS were similar between groups at baseline (p > 0.05), exercise training significantly increased IS in FH− and FH+ (FH‐: 3.01 ± 0.38 to 4.16 ± 0.35; FH+: 3.86 ± 0.61 to 4.16 ± 0.35 mg/kg EMBS/min; two‐way ANOVA p = 0.0005). FBG did not change with exercise training (p > 0.05). Baseline miRNA‐29a expression was not different between FH− and FH+ (−3.82 ± 4.92 vs. 3.56 ± 1.48, respectively; p = 0.17) and was not significantly affected by exercise training (FH‐: −3.82 ± 4.92 to 6.07 ± 3.64; FH+: 3.56 ± 1.48 to −3.33 ± 4.68; two‐way ANOVA p = 0.57). In FH+, there was a negative association between the exercise training‐induced reductions in miRNA‐29a and baseline FBG (r 2 = 0.48, p = 0.05). In FH‐, there was a negative association between exercise‐induced reductions in miRNA‐29a and improvements in IS that approached significance (r 2 = 0.56, p = 0.08). Conclusions Insulin sensitivity was not impaired in young, sedentary men with a family history of type 2 diabetes and improved IS regardless of FH status, suggesting that the extent of metabolic abnormalities in offspring of diabetes patients may vary in early adulthood. In a normoglycemic population, subjects with the highest fasting glucose levels and a family history of diabetes displayed the greatest reductions in miRNA‐29a expression. These findings suggest that reductions in circulating miRNA‐29a with exercise training may be associated with improvements in insulin sensitivity. Support or Funding Information Dodson Research Grant, The University of Texas at El Paso ‐ Graduate School Bajpeyi Lab This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .