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
Glycolysis the neighboring pancreatic alpha cells to release glucagon into the blood. This, in turn, causes the liver to release glucose into the blood by breaking down stored glycogen, and by means of gluconeogenesis. If the fall in the blood glucose level is particularly rapid or severe, other glucose sensors cause the release of epinephrine from the adrenal glands into the blood. This has the same action as glucagon on glucose metabolism, but its effect is more pronounced. In the liver glucagon and epinephrine cause the phosphorylation of the key, rate limiting enzymes of glycolysis, fatty acid synthesis, cholesterol synthesis, gluconeogenesis,