Figure 3: Insulin secretion and removal from the general circulation depend on pancreatic activity and from the clearance exerted by various organs: liver (-50%), kidney (-30%), muscles (-15 to -35%).

Insulin secretion from β cells of Langherhans islets of the pancreas derives from cleavage of pro-insulin into insulin and C-peptide, and the these products are secreted into the portal vein. The blood passes through the liver, which extracts about 50% of the newly secreted insulin. The remaining insulin exits from liver and enters into the systemic arterial circulation via the hepatic veins. The remaining amount of insulin is removed while passing through the kidneys and the muscles. Whenever liver clearance ability is impaired, a lower amount of insulin is degraded.