Muscle type-dependent responses to insulin in intramyocellular triglyceride turnover in obese rats

Objective: To understand the role of hyperinsulinemia in intramyocellular (imc) triglyceride (TG) accumulation and in regulating imcTG turnover. Research Methods and Procedures: imcTG was first prelabeled by continuous infusion Of [U-C-14] glycerol (pulse), and then the rate of label loss from the prelabeled imcTG Pool (turnover) in gastrocnemius, tibialis anterior, and soleus muscle of awake, high-fat-fed obese rats during the Subsequent hyperinsulinemic-euglycemic clamp experiments (chase) was determined. Results: Post-absorptive basal fractional imcTG turnover rate in soleus was 0.010 +/- 0.001/min, significantly lower than that in gastrocnemius (0.026 +/- 0.002/min, p<0.001) or tibialis anterior (0.030 +/- 0.002/min, p<0.0001), a pattern reciprocal to their imcTG pool size. Insulin infusion at 25 pmol/kg per minute resulted in pathophysiological hyperinsulinemia (5-fold increase over the baseline value). This caused an increase in imcTG turnover by 3-fold in soleus (0.029 +/- 0.006/min, p=0.002) but a decrease in gastrocnemius (0.012 +/- 0.003/min, p=0.001) and in tibialis anterior (0.0064 +/- 0.001/min, p<0.0001). Pathophysiological hyperinsulinemia suppressed hormone-sensitive lipase activity in heart (p=0.01) and mesenteric fat (p=0.05) but not in skeletal muscle (p>0.05). The pool size of imcTG was not affected by hyperinsulinemia. Discussion: The results demonstrated muscle-type dependence in the response of imcTG turnover to hyperinsulinemia in the obesity model. The reciprocal insulin effects on imcTG turnover in oxidative vs. oxidative-glycolytic muscle indicated a possibility that oxidative muscle contributes more to insulin resistance under hyperinsulinemia if imcG-fatty acid oxidation is a function of turnover. imcTG turnover does not seem to regulate imcTG pool size acutely.