ZengKui Guo

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 [14C]glycerol, [14C]glucose, and [3H]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.

Peroxisome proliferator-activated receptor gamma agonism modifies the effects of growth hormone on lipolysis and insulin sensitivity

Context  Peroxisome proliferator‐activated receptor gamma (PPAR‐γ) agonists such as thiazolidinediones (TZDs) improve insulin sensitivity in type 2 diabetes mellitus (T2DM) through effects on fat metabolism whereas GH stimulates lipolysis and induces insulin resistance.