Effect of insulin-like factors on glucose transport activity in unweighted rat skeletal muscle.

Abstract

We have previously demonstrated that mechanical unweighting of the soleus muscle by hindlimb suspension leads to increases in insulin receptor binding, muscle/fat-specific glucose transporter (GLUT-4) protein levels, and insulin-stimulated glucose transport activity. The present study used a novel approach to further evaluate the potential role of postreceptor binding mechanisms in this enhanced insulin effect after unweighting. Insulin-like growth factor I (IGF-I), vanadate, and phospholipase C were used to stimulate glucose transport activity independently of insulin receptor binding. Soleus glucose transport activity (assessed by 2-deoxyglucose uptake) was evaluated in vitro with soleus strips (approximately 18 mg). Progressively increased responses to maximally effective doses of insulin or IGF-I were observed after 3 and 6 days of unweighting compared with weight-matched control strips. Enhanced maximal responses to vanadate (6 days only) and phospholipase C (3 and 6 days) for 2-deoxyglucose uptake were also observed. The results of this study 1) provide evidence that post-insulin receptor binding mechanisms also play a role in the enhanced response of the insulin-dependent pathway for stimulation of glucose transport in unweighted skeletal muscle and 2) indicate that IGF-I action on glucose transport is included in this enhanced response in unweighted muscle.