Sex differences in insulin regulation of skeletal muscle glycogen synthase and changes during weight loss and exercise in adults

Abstract

AbstractObjectiveThe authors sought to understand sex differences in muscle metabolism in 73 older men and women.MethodsBody composition, VO2max, and insulin sensitivity (M) by 3‐hour hyperinsulinemic‐euglycemic clamp with vastus lateralis muscle biopsies were measured.ResultsWomen had lower body weight, VO2max, and fat‐free mass than men. Men had lower M, lower change (insulin minus basal) in muscle glycogen synthase (GS) activity, and lower change in AKT protein expression than women. M was associated with the change (insulin‐basal) in GS activity and the change in AKT protein expression. Sex differences (n = 60) were tested with 6‐month weight loss or 3×/week aerobic exercise training. The postintervention minus preintervention change (insulin‐basal) (∆∆) in GS activity (fractional, independent, total) was higher in men than women in the weight loss group and ∆∆ in GS fractional activity was higher in women than men in the aerobic exercise group. In all participants, ∆∆ in GS fractional and independent activities was related to ∆∆ in AKT expression and glycogen content.ConclusionsSex differences in insulin sensitivity may be explained at the cellular muscle level, and to improve skeletal muscle insulin action in older adults, it may be necessary to recommend different behavioral strategies depending on the individual's sex.