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.


METHODS
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.


CONCLUSIONS
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.
Guo
Zengkui
Z
Endocrine Research Unit, Mayo Foundation, Rochester, MN 55905, USA. guo.zengkui@mayo.edu
Zhou
Lianzhen
L
D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000032:analysis / Q000097:blood; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D002787:Sterol Esterase / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D002787:Sterol Esterase; D005990:Glycerol