Prolonged Incubation of Isolated Rat Skeletal Muscle under Conditions of Simulated Calorie Restriction (Reduced Glucose and Insulin) Induces to Increased Insulin-Stimulated Glucose Transport.

Arias, Edward B.; Cartee, Gregory D.

Increased insulin sensitivity in skeletal muscle is a hallmark of calorie restriction (CR; consuming 60% of ad libitum, AL, intake). In vivo CR is a complex intervention, making it difficult to isolate the specific CR-induced events that trigger the improved insulin sensitivity in skeletal muscle. Thus, it would be useful to develop an in vitro muscle model which could "simulate" specific aspects of CR. We hypothesized that incubation of rat epitrochlearis muscles with decrements in extracellular glucose (simulated AL=8mM; simulated CR=5.5mM) and/or insulin (simulated AL=0.48nM; simulated CR=0.12nM) similar to those found with CR would result in increased insulin-stimulated glucose transport. In muscles incubated under these conditions for 24hr, reducing either insulin or glucose independently did not alter basal or insulin-stimulated glucose transport (measured using 8mM 3-O-methylglucose ±0.48nM insulin) vs. contralateral muscles incubated for 24hr with simulated AL media. However, simultaneously reducing both insulin and glucose to simulated CR levels resulted in a significant increase (29%; P<0.005) in glucose transport of insulin-stimulated muscles vs. contralateral controls incubated for 24hr with simulated AL glucose and insulin. To better delineate the amount of time required for the increased glucose transport, we evaluated the effect of simulated CR (reduced glucose and insulin) for 6hr and found no effect on glucose transport. These results support the idea that in vivo CR-induced reductions in both glucose and insulin may together be necessary and sufficient for inducing at least a portion of the increased insulin sensitivity in skeletal muscle. This simulated CR model will be useful to elucidate the mechanisms that account for increased glucose transport and to determine if these adaptations are similar to those found with in vivo CR.

STRIATED muscle; LABORATORY rats; LOW-calorie diet; BLOOD sugar; INSULIN

Diabetes, 2007, Vol 56, pA661

0012-1797

Academic Journal