Effect of unloading by tail-cast suspension on carbohydrate metabolism in skeletal muscle.

Abstract

The tail-cast suspension system was used as a ground-based model of weightlessness to study the effects of reduced weight-bearing (unloading) and attendant atrophy on carbohydrate metabolism in the rat soleus muscle. Changes in glycogen metabolism during unloading were biphasic. The initial phase, which took place during the first 24 hours, was characterized by increased glycogen concentrations, the result of decreased glycogenolysis. This glycogen accumulation in turn decreased the glycogen synthase activity ratio. These alterations were maintained thereafter. A similar glycogen increase was seen in the soleus unloaded by hypogravity. A rapid decline in glucose uptake also occurred during this initial phase of unloading, both in the absence and presence of insulin. During the second phase of this unloading response, beyond 24 hours, there was an increase in the sensitivity of the soleus to insulin for glucose uptake that coincided with the onset of muscle atrophy. However, this increased insulin sensitivity was not seen for glycogen synthesis, indicating differential regulation of these two processes by insulin. The enhanced insulin sensitivity likely resulted from an increase in the binding capacity for the hormone, resulting from no increased turnover of the insulin receptor during unloading. Additionally, the onset of increased insulin sensitivity coincided with a return to normal of basal glucose uptake, despite the continued unloading. When the 3-day unloaded soleus was reloaded, carbohydrate metabolism returned to normal after a triphasic response. Within two hours, the glycogen concentration decreased below control levels, due to increased glycogenolysis. During the second phase of reloading, from two to 24 hours, glycogen accumulated dramatically due to an enhanced capacity of the muscle for glycogenesis. Insulin sensitivity returned to normal by 24 hours of reloading. In the final phase, beyond 24 hours, glycogen decreased to control values. An uncoupling of the inverse relationship between glycogen and the activity ratio of glycogen synthase was seen beyond four hours of reloading. These effects of unloading and reloading were not due to systemic factors, as the extensor digitorum longus was unaffected. It is apparent that the unloaded soleus is a potent model with which to study the individual factors that regulate carbohydrate metabolism in skeletal muscle.