Human proinsulin is converted into one molecule of insulin and one molecule of C-peptide in the insulin secretory granule of the pancreatic β cell. Approximately 50% of the secreted insulin is extracted by the liver on the first pass, and the fraction undergoing hepatic extraction varies under different physiological and pathophysiological conditions. Thus, peripheral insulin concentrations reflect posthepatic insulin delivery rather than insulin secretion. C-peptide is not metabolized by the liver, and its peripheral concentration more accurately reflects it secretion rate and therefore that of insulin, since they are co-secreted.