Abstract
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-14C]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 im-cTG-fatty acid oxidation is a function of turnover. imcTG turnover does not seem to regulate imcTG pool size acutely.
Original language | English (US) |
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Pages (from-to) | 2081-2087 |
Number of pages | 7 |
Journal | Obesity research |
Volume | 13 |
Issue number | 12 |
DOIs | |
State | Published - 2005 |
Keywords
- Insulin
- Skeletal muscle
- Triglyceride turnover
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Food Science
- Endocrinology, Diabetes and Metabolism
- Endocrinology
- Public Health, Environmental and Occupational Health