The effect of diet on multiple site regulation of glycolysis in rat skeletal muscle. 1. Glucose metabolism and intracellular metabolites

Abstract

The relationship between diet and insulin responsiveness was examined in isolated Extensor Digitorum Longus and Soleus muscle from 6-wk-old female Sprague-Dawley rats. Rats were fed either a high fat (HF) (67%kcal) or high carbohydrate (HC) (67%kcal) diet for 21 days, ad libitum. Plasma insulin decreased while plasma glucose values were increased in the HF-fed rats compared with HC-fed controls. The mechanisms responsible for the insulin resistant state were studied by measuring 2-deoxyglucose uptake, glucose metabolism [F6P], [F1, 6BP], [F2, 6BP] in EDL and soleus muscles under basal and maximally insullin-stimulated conditions. Basal and maximal insulin stimulated 2-Deoxyglucose uptake was significantly lower in EDL and soleus muscle from HF-fed rats when compared with high carbohydrate controls. High fat feeding produced a decrease in post membrane basal and insulin-stimulated glucose utilization and varied depending upon pathway and muscle type involved. An estimate of glycolysis ( 3H 2O formation from [5 − 3H]glucose) and glucose oxidation ( 14CO 2 production from 14C-glucose) demonstrated a greater decrease in basal and insulin stimulated utilization than did [5- 3H]glucose conversion to 3H-glycogen. Total glucose utilization was significantly greater in EDL muscle compared to soleus muscle independent of dietary treatment. Insulin failed to increase [F6P] or [F1, 6BP] in EDL or soleus muscle from high fat fed rats. However, insulin did increase [F6P] and F1, 6BP] in soleus, while producing a decrease in [F6P] in EDL muscle from high carbohydrate fed rats. Insulin stimulation produced a significant increase in F2, 6BP in both muscle types in HF-fed rats. However, no increases in F2, 6BP were observed in HC-fed rats in either muscle type. These data demonstrate that increased dietary fat leads to an impairment of insulin action, in multiple muscle types, particularly with respect to the glycolytic pathway. Furthermore, this impairment appears to involve, in part, the conversion of F6P to F1, 6BP.