Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity

Abstract

Aims/hypothesis: In skeletal muscle, ceramides may be involved in the pathogenesis of insulin resistance through an attenuation of insulin signalling. This study investigated total skeletal muscle ceramide fatty acid content in participants exhibiting a wide range of insulin sensitivities.

Methods: The middle-aged male participants (n=33) were matched for lean body mass and divided into four groups: type 2 diabetes (T2D, n=8), impaired glucose tolerance (IGT, n=9), healthy controls (CON, n=8) and endurance-trained (TR, n=8). A two step (28 and 80 mU m(-2) min(-1)) sequential euglycaemic-hyperinsulinaemic clamp was performed for 120 and 90 min for step 1 and step 2, respectively. Muscle biopsies were obtained from vastus lateralis at baseline, and after steps 1 and 2.

Results: Glucose infusion rates increased in response to insulin infusion, and significant differences were present between groups (T2D<IGT<CON<TR). At baseline, muscle ceramide content was 108+/-7, 95+/-6, 126+/-12 and 156+/-25 nmol total ceramide fatty acids/g wet weight of tissue in the T2D, IGT, CON and TR groups, respectively, and muscle ceramide content was higher (p<0.01) in the TR than the IGT group. Muscle ceramide content was not influenced by insulin infusion. Interestingly, a positive correlation (r=0.42, p<0.05) was present between muscle ceramide content at baseline and insulin sensitivity.

Conclusions/interpretation: Total muscle ceramide content was similar between individuals showing marked differences in insulin sensitivity, and therefore does not seem to be a major factor in muscle insulin resistance. Furthermore, aerobic capacity does not appear to influence muscle ceramide content.