Intact regulation of muscle expression and circulating levels of myokines in response to exercise in patients with type 2 diabetes

Abstract

Regular exercise plays an important role in the prevention and treatment of type 2 diabetes (T2D). The synthesis and secretion of myokines in response to contraction may contribute to the beneficial metabolic effects of exercise. However, some exercise-induced responses may be attenuated in T2D. Here, we investigated whether the effect of acute exercise on selected myokines are impaired in T2D. Skeletal muscle biopsies and blood samples were obtained from 13 men with T2D and 14 weight-matched, glucose-tolerant men before, immediately after and 3-h after acute exercise (60 min cycling) to examine muscle expression and plasma/serum levels of selected myokines. One-hour of exercise increased muscle expression of IL6, FGF21, ANGPTL4, CHI3L1, CTGF and CYR61, of which FGF21, ANGPTL4 and CHI3L1 increased further 3-h into recovery, whereas expression of IL6, CYR61, and CTGF returned to baseline levels. There was no immediate effect of exercise on IL15 expression, but it decreased 3-h into recovery. Plasma IL-6 increased robustly, whereas circulating levels of FGF21, ANGPTL4, IL-15, and CHI3L1 increased only modestly in response to exercise. All returned toward baseline levels 3-h into recovery except for plasma ANGPTL4, which increased further. No significant differences in these responses to exercise were observed between the groups. Our results demonstrate that muscle expression and circulating levels of selected known and putative myokines were equally regulated by acute exercise in patients with T2D and weight-matched controls. This suggests that the potential beneficial metabolic effects of these myokines are not impaired in patients with T2D.

Keywords: Exercise resistance; T2D; myokines; skeletal muscle.

Figure 1

Muscle expression and plasma levels of IL‐6 and IL‐15. (A) IL6 mRNA, (B) Plasma IL‐6, (C) IL15 mRNA and (D) Plasma IL‐15 in patients with T2D (black bars, ∎) and healthy controls (white bars, ○) before (Basal) and immediately after 60 min of exercise at 70% VO _2max (Exercise) and 3‐h into recovery (3‐h Rec.). Values are means ± SEM. mRNA levels were measured in n = 13 controls and n = 10 patients with T2D. ***P < 0.001 versus Basal (main effect), and ^§§§ P < 0.001 versus Exercise (main effect).

Figure 2

Muscle expression and serum levels of FGF21. (A) FGF21 mRNA and (B) Plasma FGF‐21in patients with T2D (black bars, ∎) and healthy controls (white bars, ○) before (Basal) and immediately after 60 min of exercise at 70% VO _2max (Exercise) and 3‐h into recovery (3‐h Rec.). Values are means ± SEM. mRNA levels were measured in n = 13 controls and n = 10 patients with T2D. *P < 0.05 and ***P < 0.001 versus basal (main effect), ^§ P < 0.05 and ^§§§ P < 0.001 versus exercise (main effect), and ^### P < 0.001 versus healthy controls (main effect).

Figure 3

Muscle expression and plasma levels of ANGPTL4 and CHI3L1. (A) ANGPTL4 mRNA, (B) Plasma ANGPTL4, (C) CHI3L1 mRNA and (D) Plasma CHI3L1 in patients with T2D (black bars, ∎) and healthy controls (white bars, ○) before (Basal) and immediately after 60 min of exercise at 70% VO _2max (Exercise) and after 3‐h into recovery (3‐h Rec.). Values are means ± SEM. mRNA levels were measured in n = 13 controls and n = 11 patients with T2D. *P < 0.05 and ***P < 0.001 versus basal (main effect), ^§§§ P < 0.001 versus exercise (main effect), and ^# P < 0.05 versus healthy controls (main effect).

Figure 4

Muscle expression of CYR61 and CTGF. (A) CYR61 mRNA and (B) CTGF mRNA in patients with T2D (black bars) and healthy controls (white bars) before (Basal) and immediately after 60 min of exercise at 70% VO _2max (Exercise) and after 3‐h into recovery (3‐h Rec.). Values are means ± SEM. mRNA levels were measured in n = 13 controls and n = 13 patients with T2D. ***P < 0.001 versus basal (main effect), and ^§§§ P < 0.001 versus exercise (main effect).