APPS November 2002 Meeting Abstract 1219

Mark A. Febbraio¹^,2,3, Adam Steensberg³^,4, Charlotte Keller^3,4, Rebecca L. Starkie^2,3, Henning B. Nielsen⁵, Peter Krustrup^3,7, Peter Ott⁵, Niels H. Secher^3,6, Bente K. Pedersen^3,4, 1 School of Medical Sciences RMIT University, Bundoora 3083, 2 Dept. of Physiology, The University of Melbourne, Parkville, 3010, Australia, 3 The Copenhagen Muscle Research Centre, The Depts. of 4 Infectious Diseases, 5 Hepatology and 6 Anesthesia Rigshospitalet, 7 The August Krogh Institute, The University of Copenhagen, DK-2100, Copenhagen Ø, Denmark.

Interleukin (IL)-6 is produced by skeletal muscle¹ but cleared by the hepatosplanchnic viscera² during exercise. While glucose ingestion during exercise reduces plasma IL-6 it has no effect on intramuscular IL-6 gene expression³. To test the hypothesis that increasing circulating glucose throughout exercise would enhance hepatosplanchnic clearance of IL-6 leading to a reduction in circulating IL-6 content, seven men performed 120 min of semi-recumbent cycling on two occasions while ingesting either a 6.4 % carbohydrate (CHO) or sweet placebo (CON) beverage throughout exercise. Muscle biopsies, obtained before and immediately after exercise were analysed for muscle glycogen and IL-6 mRNA expression. Blood samples were simultaneously obtained from a brachial artery, a femoral vein and the hepatic vein prior to and during exercise for the analysis of IL-6, glucose and free fatty acids (FFA). Leg blood flow was measured by thermodilution in the femoral vein, and hepatosplanchnic blood flow was measured using indocyanine green infusion. Net leg and net hepatosplanchnic IL-6, glucose and FFA balance were calculated from these measures. Consistent with our previous study³, arterial IL-6 concentration was lower (P<0.05) throughout exercise in CHO, but neither intramuscular glycogen nor IL-6 mRNA within skeletal muscle was different when comparing CHO with CON. Contrary to our hypothesis, hepatosplanchnic IL-6 clearance was not affected by glucose availability, but rather appeared to be regulated by IL-6 delivery, since it was lower (P<0.05) after 120 min in CHO compared with CON. Even though IL-6 mRNA was similar when comparing trials, net leg IL-6 release was markedly attenuated (P<0.05) in CHO compared with CON. This corresponded to an enhanced (P<0.05) glucose uptake and reduced (P<0.05) FFA uptake in CHO compared with CON. These results demonstrate that increasing circulating glucose during exercise attenuates IL-6 release from, but not mRNA expression within, contracting human skeletal muscle. It appears that while IL-6 gene expression is regulated, in part, by glycogen content^1,4, IL-6 release is influenced by substrate flux across the contracting limb.