Abstract 11160: Six Weeks High Fat Diet Does Not Reduce Access of Insulin to Skeletal Muscle
Endothelial function allows dispersion of blood through muscle and thus increases insulin delivery to myocytes, but we have shown that diet-induced insulin resistance reduces dispersion of insulin through skeletal muscle. Thus, we expected that endothelial dysfunction in the diet-induced canine model would reduce the amount of insulin detected in the interstitial fluid. Anesthetized dogs were exposed to basal insulin levels for 180min followed by hyperinsulinemia (1mU/min/kg); glucose was infused at a variable rate to maintain euglycemia. Fat feeding reduced the glucose infusion rate (lean 11.7±1.1mg/min/kg, vs obese 8.1±0.8mg/min/kg, P=0.02), indicating insulin resistance. At the end of the clamp, arterial insulin was 80.6±10.4mU/L in lean animals, compared to 93.0±5.0 in obese animals (n=8 per group), while lymph (interstitial) insulin concentrations were 63.4±11.5 and 55.0±4.4mU/L in lean and obese respectively. At steady state, the ratio of lymph:plasma insulin was 0.41±0.04 (lean) and 0.49±0.09 (obese) at basal insulin concentrations (NS), and 0.58±0.02 (lean) and 0.59±0.03 (obese) at high insulin concentrations (NS), suggesting no significant impairment in insulin access to the interstitial space after 6 weeks of fat feeding. Preliminary results in animals after 6 months fat feeding appear to show that insulin access is also not reduced, and possibly even increased (ratio of lymph:plasma insulin of 0.40 at basal, and 0.75 at high insulin concentrations). Cellular insulin sensitivity was decreased by 6 weeks of a high fat diet (SIcellular = ΔGINF/(Δlymph insulin x Glucose) (lean 2.76±0.44, vs obese 1.62±0.18 dl/min/kg per μU/ml, P=0.02) and did not appear to be further affected by 6 months high fat diet (1.72 dl/min/kg per μU/ml). Therefore we conclude that insulin resistance induced by high fat diet is due to cellular insulin resistance in our model, rather than endothelial dysfunction causing reduced insulin access. Further experiments will assess insulin access under lower insulin concentrations, measure dispersion of blood through muscle, and validate lymph sampling in this insulin resistant model.
- © 2013 by American Heart Association, Inc.