But what about the muscle? After all, it would do little good to increase insulin resistance everywhere only to have the working muscle suffer the same fate. Fortunately, the body has a wonderful interplay of systems. Glucose (sugar) from the blood is taken into muscle through transporters called GLUT4 transporters. In resting conditions, these transporters are held inside the muscle cell so that this large tissue mass does not rob the vital organs of energy. However, when insulin stimulates receptors on the muscle cell surface, the GLUT4 transporters rush to the cell membrane and start taking in their share of the calories provided by a meal.18 Obviously, if there is an excess of IL6, this mechanism would seem to function poorly and sugar control would be affected throughout the whole body.19 This is the case seen in rodents. In contrast, studies in humans have shown the opposite, with insulin concentrations dropping and glucose getting shuttled into and burned for calories quicker, as well as an increase in fatty acid oxidation (calorie burning).20,21 In fact, some leading researchers believe the overall effect of IL6 is insulin sensitizing in humans.

This may sound like a wonderful condition, but prolonged exposure to IL6 would not necessarily be a positive situation. Remember, the fat cells have an important role in buffering fatty acid concentrations. Otherwise, negative effects such as insulin resistance and atherosclerosis become pathologic. Thus, it would seem that IL6 could be a very positive player if its release was controlled and related to a situation where fat and sugar calories were burned quickly.
Sounds like exercise, doesn’t it? Exactly so. An interesting observation was noted that contracting muscle generates a number of physiologic modifiers. Many people are familiar with lactic acid, but guess what other major factor is released during exercise by contracting muscle? That’s right, IL6. Exercise is sometimes called a metabolic sink because it is a unique physiologic condition that is associated with a tremendous increase in the metabolism of the body in general and muscle in particular.8 One relevant effect of muscle contraction that is often not accounted for is the insulin-independent glucose uptake. When a muscle contracts, it causes GLUT4 transporters to migrate to the cell membrane so that the muscle can grab sugar from the bloodstream to use for energy, without needing to be stimulated by insulin.22 So, the working muscle is protected from any potential insulin resistance effect of IL6 during exercise. Remember, in humans IL6 is believed to increase insulin sensitivity in muscle, not insulin resistance, so its effect would be to enhance glucose uptake by exercising muscle.7,20