Acute hyperinsulinemia inhibits intramyocellular triglyceride synthesis in high-fat-fed obese rats.
Hyperinsulinemia is common in obesity, but whether it plays a role in intramyocellular triglyceride (imcTG) buildup is unknown. In this study, hyperinsulinemic-euglycemic clamp experiments were performed in overnight-fasted lean and high-fat-fed obese rats, awake, to determine the effect of insulin on imcTG synthesis (incorporation of [(14)C]glycerol, [(14)C]glucose, and [(3)H]oleate). Insulin infusion at 25 (low insulin) and 100 (high insulin) pmol/kg/min increased plasma insulin by 5- and 16-fold, respectively, whereas plasma and intramyocellular glycerol, FFAs, triglycerides, and glucose levels were maintained at their basal levels by co-infusion of exogenous glycerol, FFAs, and triglycerides at fixed rates and glucose at varying rates. In obese rats, insulin suppressed incorporation of glycerol into the imcTG-glycerol moiety dose dependently (P < 0.01-P < 0.001) in gastrocnemius and tibialis anterior, but only the high insulin suppressed it in soleus (P < 0.05). The low insulin suppressed glucose incorporation into imcTG-glycerol in all three muscles (P = 0.01-P < 0.01). However, the low insulin did not affect (P > 0.05) and the high insulin suppressed (P < 0.05-P < 0.01) fatty acid incorporation into imcTG in all three muscles. Insulin also suppressed glycerol incorporation in lean rats (P < 0.01-P < 0.04). On the other hand, imcTG pool size was not affected by insulin (P > 0.05). These observations suggest that acute hyperinsulinemia inhibits imcTG synthesis and thus does not appear to promote imcTG accumulation via the synthetic pathway, at least in the short term.
Guo
Zengkui
Z
Endocrine Research Unit, Mayo Foundation, Rochester, MN 55905, USA. guo.zengkui@mayo.edu
Zhou
Lianzhen
L
Jensen
Michael D
MD
D000208:Acute Disease; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000378:metabolism; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000096:biosynthesis*
D001786:Blood Glucose; D004041:Dietary Fats; D005227:Fatty Acids; D014280:Triglycerides; D005947:Glucose; D005990:Glycerol