Christian de Duve glucagon was the major hormone influencing the breakdown of glycogen (glycogenolysis) in the liver, by which more sugars are produced in the blood. De Duve's original hypothesis that glucagon was produced by pancreatic alpha cells was proved right when it was demonstrated that selectively cobalt-damage alpha cells stopped producing glucagon in guinea pigs, and finally isolated the purified hormone in 1953, including those from birds. De Duve was the first to hypothesise that production of insulin to decrease blood sugar level stimulated the uptake of glucose in the liver, and that there is a balanced production of insulin and glucagon
Glycogen is referred to as "hitting the wall". Glycogen depletion can be forestalled in three possible ways. First, during exercise, carbohydrates with the highest possible rate of conversion to blood glucose (high glycemic index) are ingested continuously. The best possible outcome of this strategy replaces about 35% of glucose consumed at heart rates above about 80% of maximum. Second, through endurance training adaptations and specialized regimens (e.g. fasting low-intensity endurance training), the body can condition type I muscle fibers to improve both fuel use efficiency and workload capacity to increase the percentage of fatty acids used as fuel, sparing carbohydrate use