Interleukin-6 is a negative regulator of hepatic glucose production in the isolated rat liver

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.