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
Glucose addition, there is also a hormone-independent regulation, which is referred to as glucose autoregulation. After food intake the blood sugar concentration increases. Values over 180 mg/dl in venous whole blood are pathological and are termed hyperglycemia, values below 40 mg/dl are termed hypoglycaemia. When needed, glucose is released into the bloodstream by glucose-6-phosphatase from glucose-6-phosphate originating from liver and kidney glycogen, thereby regulating the homeostasis of blood glucose concentration. In ruminants, the blood glucose concentration is lower (60 mg/dL in cattle and 40 mg/dL in sheep), because the carbohydrates are converted more by their gut flora into short-chain fatty acids.