NEURAL CONTROL OF GLUCOSE-UPTAKE BY SKELETAL-MUSCLE AFTER CENTRAL ADMINISTRATION OF NMDA

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produ ces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are respo nsible for the elevated rate of glucose disposal. NMDA was injected in tracerebroventricularly, and the glucose metabolic rate (R(g)) was det ermined for individual tissues 20-60 min later using 2-deoxy-D-[U-C-14 ]glucose. NMDA decreased R(g) in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, R(g) in skel etal muscle and heart was increased 150-160%. This increased R(g) was not due to an elevation in plasma insulin concentrations. In subsequen t studies, the sciatic nerve in one leg was cut 4 h before injection o f NMDA. NMDA increased R(g) in the gastrocnemius (149%) and soleus (22 0%) in the innervated leg. However, R(g) was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third s eries of experiments indicated that the NMDA-induced increase in R(g) by innervated muscle and its abolition in the denervated muscle were n ot due to changes in muscle blood flow. The results of the present stu dy indicate that 1) central administration of NMDA increases whole bod y glucose uptake by preferentially stimulating glucose uptake by skele tal muscle, and 2) the enhanced glucose uptake by muscle is neurally m ediated and independent of changes in either the plasma insulin concen tration or regional blood flow.