The mechanism underlying the increased rate of endogenous glucose production from the liver during exercise remains unknown. The cytokine interleukin-6 (IL-6) is known to be released during exercise and is thought that either IL-6 directly or via a "contraction factor" stimulates the release of stored glucose from the liver. Here we show that IL-6 does not directly increase hepatic glucose output (HGO). Moreover, IL-6 infused at the same time as glucagon caused a significant reduction in HGO. IL-6 infused with epinephrine caused no synergenic increase in HGO. To test if an unknown "contraction factor" was needed along with IL-6 to increase HGO, we used human fasted and exercised plasma perfused with or without IL-6 in our isolated liver system. We found that exercised plasma increased HGO, as expected, but when infused with IL-6, reductions in HGO were found. Our results provide evidence that IL-6 works as a negative regulator of HGO.
Keywords: Exercise; glucagon; hepatic glucose production; interleukin-6.