The concentration of glucose in the blood is the result of a balance between food intake and glucose mobilization from the liver, on the one hand, and its consumption by the tissues on the other. The former is regulated by many hormones but the latter only by insulin.

During feeding, increased blood glucose and amino acid levels, as well as gut hormones, stimulate insulin secretion from the cells of the pancreas. The main action of insulin is in the liver where it stimulates conversion of glucose to glycogen and decreases gluconeogenesis and glycogenolysis. The liver consumes much of the insulin secreted so that an assessment of endogenous insulin secretion into the portal vein has to be made by the measurement of plasma C (connecting) peptide concentrations in peripheral blood. C peptide is split from pro-insulin in equimolar amounts but is not removed by the liver. The insulin which gets through the liver is diluted in the extracellular volume but still exerts profound peripheral effects stimulating uptake of glucose and amino acids by muscle and of glucose by fat cells to form triglyceride.

During fasting, the blood glucose concentration falls, insulin production reduces under the influence of pancreatic somatostatin and glucagon is secreted by the pancreatic α cells. The falling glucose level is sensed in the hypothalamus which regulates pancreatic secretion by neural mechanisms and stimulates release of ACTH (and thereby cortisol), GH, prolactin and catecholamines.