Opposite effects of acute hypoglycemia and acute hyperglycemia on glucose transport and glucose transporters in perfused rat skeletal muscle

This study was undertaken to characterize the effects of glycemia per se (g lucose effectiveness) on muscle glucose transport. Isolated rat hindlimbs w ere perfused in situ for 2 h with perfusate containing either low (2 mmol/l , n = 7), normal (6.5 mmol/l, n = 6), or high (20 mmol/l, n = 6) concentrat ions of glucose, without insulin, to simulate hypo-, eu-, and hyperglycemic conditions. The effect of varying glucose concentrations on muscle glucose transport was assessed by an ensuing 30-min perfusion with 5.5 mmol/l gluc ose perfusate without insulin. The 2-h of low glucose perfusion induced sig nificant increases in both muscle glucose clearance (similar to 2.3-fold, P < 0.01) and plasma membrane GLUT4 content (similar to 20%, P < 0.05) relat ive to normal. In contrast, high glucose perfusion decreased glucose cleara nce (similar to 1.7-fold, P < 0.01) and plasma membrane GLUT4 content (simi lar to 20%, P < 0.05). Glucose extraction during the following 30-min perfu sion was 2.5-fold greater (P < 0.0001) in the low group and threefold less (P < 0.0001) in the high group, relative to normal. 2-[H-3]deoxyglucose-6-p hosphate content in both red (soleus) and white (extensor digitorum longus) muscles increased approximately twofold after 2 h of low glucose perfusion (P < 0.0001) and decreased greater than or equal to 2-fold after high gluc ose perfusion (P < 0.0001), relative to normal. It is concluded that glycem ia regulates glucose transport in skeletal muscle independently of insulin, achieved at least partially via changes in plasma membrane GLUT4. We propo se that high glucose levels can acutely downregulate GLUT4 and glucose clea rance, thus limiting excessive glucose uptake in muscle. Conversely, low gl ucose-induced upregulation of muscle glucose clearance and GLUT4 can compen sate for reduced glucose availability in the circulation.