Central Administration of IL-1α Increases Glucose Uptake by Muscle

Intracerebroventricular (ICV) injection of interleukin (IL)-1α has previously been demonstrated to enhance the rate of whole body glucose disposal. The purpose of the present study was to identify the specific tissue(s) responsible for the increased glucose uptake. All experiments were performed on fasted catheterized rats in which an ICV cannula had also been implanted. In vivo glucose uptake by individual tissues was determined, using tracer amounts of [ 14C]-2-deoxyglucose, 20-60 min after the ICV injection of recombinant human IL-1α (100 ng/rat). IL-1 increased glucose uptake in skeletal muscle (117%), diaphragm (50%) and heart (110%), compared to time-matched control animals. Glucose uptake by other tissues, including the liver, spleen, lung, skin, ileum and whole brain, was not different from control values. As a result of these changes, the contribution of skeletal muscle to whole body glucose disposal increased from 29% to 48%, while that of skin and intestine decreased. The increased glucose uptake in various muscles was consistent with the increased (55%) plasma insulin levels in these animals. In rats pretreated with somatostatin, which produced severe insulinopenia, the IL-1 induced increases in glucose uptake were prevented in heart and diaphragm, and attenuated by more than 80% in skeletal muscle. These data indicate that the increased whole body glucose disposal produced by ICV injection of IL-1α was due to an enhanced uptake of glucose by muscle via insulin-mediated pathways. A comparison of the present findings with those obtained in a previous study, in which IL-1 was injected intravenously at a dose sufficient to increase whole body glucose uptake, indicates significant differences in regional glucose distribution between these two conditions.