History, Normal Physiology, and Production of Insulin

Abstract

Insulin is produced in the pancreas, where it is secreted from beta cells located in the islets of Langerhans. The islets are surrounded by exocrine tissue but have a rich vascular and neural supply. Insulin-secreting beta cells constitute 85 % of the cells of the islets. The other endocrine cells—alpha and delta cells—produce the hormones glucagon and somatostatin, respectively, and pancreatic polypeptide is secreted from other cells. Insulin is synthesized and stored as proinsulin, which consists of two chains of amino acids, an A and B chain, joined by a connecting peptide, C-peptide (Fig. 1.1). C-peptide is split off by beta cell peptidases; insulin and C-peptide are secreted in equimolar amounts. Insulin is released into the portal circulation. An awareness of the relationship between insulin and C-peptide has practical applications, as manufactured insulin does not contain C-peptide. Measurement of C-peptide is, therefore, a useful way to differentiate between hypoglycemia secondary to exogenous insulin administration (plasma insulin is elevated; C-peptide is low or absent) and hypoglycemia secondary to endogenous hyperinsulinemia, as in the case of sulfonylurea excess or an insulinoma (insulin and C-peptide are both elevated).