title: Muscle type-dependent responses to insulin in intramyocellular triglyceride turnover in obese rats.
abstract: 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.
authors.affiliation: Endocrine Research Unit, Mayo Foundation, Rochester, MN 55905, USA. guo.zengkui@mayo.edu
authors.forename: Zengkui
authors.initials: Z
authors.lastname: Guo
authors.forename: Lianzhen
authors.initials: L
authors.lastname: Zhou
mesh_terms: 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*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D002787:Sterol Esterase; D005990:Glycerol