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-(14)C]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 imcTG-fatty acid oxidation is a function of turnover. imcTG turnover does not seem to regulate imcTG pool size acutely.