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 synthase expression of the muscle isozyme and not the liver isozyme. However, muscle-specific glycogen synthase activation may lead to excessive accumulation of glycogen, leading to damage in the heart and central nervous system following ischemic insults. The reaction is highly regulated by allosteric effectors such as glucose-6-phosphate (activator) and by phosphorylation reactions (deactivating). Glucose-6-phosphate allosteric activating action allows glycogen synthase to operate as a glucose-6-phosphate sensor. The inactivating phosphorylation is triggered by the hormone glucagon, which is secreted by the pancreas in response to decreased blood glucose levels. The enzyme also cleaves the ester bond between the C1 position of glucose