Abstract 15358: Aerobic Exercise Training-Induced Increase in Muscle-Derived Follistatin-Like 1 (FSTL1) Secretion is Associated With Nitric Oxide Production in Type 2 Diabetic Rats.

Introduction: Follistatin-like 1 (FSTL1) is a muscle-derived myokine and binds to FSTL1 receptor (DIP2A). FSTL1 promotes phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt in endothelial cells. However, it is unclear whether muscle-derived FSTL1 secretion induced by aerobic exercise training is related to a reduction of arterial stiffness in type 2 diabetic rats. Hypothesis: Muscle-derived FSTL1 secretion induced by aerobic exercise training is related to a reduction of arterial stiffness via elevation of NO production in type 2 diabetic rats. Methods: Twenty-week-old male type 2 diabetic (OLETF) rats were randomly divided into two groups; 8-week sedentary control (OLETF-Con: n=10) and aerobic exercise training (OLETF-Ex: treadmill running for 60min at 25m/min, 5days/week: n=7) and nine male LETO rats used as healthy sedentary control. After 8-week, we measured carotid-femoral pulse wave velocity (cfPWV: as an indicator of arterial stiffness), and artery and gastrocnemius muscle were isolated after collection of blood. Results: Fasting blood glucose and cfPWV significantly increased (p<0.05) and arterial Akt and eNOS phosphorylation and nitrate/nitrite (NOx) levels, muscle and plasma FSTL1 protein levels significantly decreased (p<0.05) in OLETF-Con rats compared to LETO rats. Aerobic exercise training significantly decreased fasting blood glucose and cfPWV (p<0.05) and significantly increased arterial Akt and eNOS phosphorylation levels, arterial NOx level, concomitantly muscle and plasma FSTL1 protein levels (p<0.05) in OLETF rats. However, no significant different of arterial DIP2A protein level among three groups were seen. Plasma FSTL1 protein level was positively correlated with arterial eNOS phosphorylation level (p<0.05, r=0.630) and arterial NOx level (p<0.05, r=0.785). Arterial NOx level was negatively correlated with cfPWV (p<0.05, r=-0.583). Conclusions: These results suggest that muscle-derived FSTL1 release induced by aerobic exercise training is related to a reduction of arterial stiffness via elevation of NO production in type 2 diabetic rats. [ABSTRACT FROM AUTHOR]