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REVERSAL OF WHOLE-BODY AND SKELETAL MUSCLE INSULIN RESISTANCE AFTER THREE AND SEVEN DAYS OF HINDLIMB SUSPENSION.  M.P. O’Keefe¹, F.R. Perez¹, T.R. Kinnick¹, and E.J. Henriksen¹. ¹Dept. of Physiology, University of Arizona, Tucson.

     We have previously detected the development of insulin resistance following 1-day of simulated weightlessness (hindlimb suspension (HS) model), as shown by increases in plasma glucose and reductions in insulin-mediated glucose uptake in soleus muscle. The specific aim of the present investigation was to test the hypothesis that HS for 3 or 7 days would lead to a reversal of whole-body insulin resistance. Four-week-old Sprague Dawley rats were assigned to either a weight-bearing (WB) control group, a 3-day HS group, or a 7-day HS group. Whole-body glucose tolerance was measured during a 1 g/kg oral glucose tolerance test (OGTT). Blood samples were taken from a tail vein at 15, 30, 60, and 90 min, and plasma was subsequently assayed for glucose and insulin concentrations. Glucose transport activity (assessed by 2-deoxyglucose uptake) was determined in isolated soleus muscle strips in the absence or presence of insulin (2 mU/ml). Three- and 7-day HS soleus had significantly lower total protein levels (-11% and -13%) and significantly higher hexokinase activity (+40% and +93%) when compared to WB soleus. Seven-day HS soleus also displayed significant elevations in citrate synthase activity (+29%) and total GLUT 4 protein levels (+62%) versus WB soleus. Suspension produced no significant difference in plasma glucose concentration, area under the curve for the glucose and insulin responses, or the glucose-insulin index when compared to the WB group. Insulin-mediated glucose transport was elevated in the HS soleus at 3 (+68%) and 7 days (+153%) when compared to WB soleus. Intramuscular triglycerides were significantly reduced at 3 day HS (-56%), and remained reduced (-38%) at 7 days of HS. In summary, these observations suggest that 3 and 7 days of simulated weightlessness in juvenile rats reverses whole-body insulin resistance observed at 1 day of HS, likely due to an enhanced capacity for insulin-stimulated glucose transport in unweighted skeletal muscle.