The endocrine pancreas in the adult human consists of approximately 1 million islets of Langerhans interspersed throughout the pancreatic gland. Within the islets, at least five hormone-producing cells are present (Table 41–1). Their hormone products include insulin, the storage and anabolic hormone of the body; islet amyloid polypeptide (IAPP, or amylin), which modulates appetite, gastric emptying, and glucagon and insulin secretion; glucagon, the hyperglycemic factor that mobilizes glycogen stores; somatostatin, a universal inhibitor of secretory cells; pancreatic peptide, a small protein that facilitates digestive processes by a mechanism not yet clarified; and ghrelin, a peptide known to increase pituitary growth hormone release.
Insulin is a small protein with a molecular weight in humans of 5808. It contains 51 amino acids arranged in two chains (A and
B) linked by disulfide bridges; there are species differences in the amino acids of both chains. Proinsulin, a long single-chain protein molecule, is processed within the Golgi apparatus of beta cells and packaged into granules, where it is hydrolyzed into insulin and a residual connecting segment called C-peptide by removal of four amino acids (Figure 41–1).
Insulin and C-peptide are secreted in equimolar amounts in response to all insulin secretagogues; a small quantity of
TABLE 41–1 Pancreatic islet cells and their secretory products.
1Within pancreatic polypeptide-rich lobules of adult islets, located only in the posterior portion of the head of the human pancreas, glucagon cells are scarce (<0.5%) and F cells make up as much as 80% of the cells.
unprocessed or partially hydrolyzed proinsulin is released as well. Although proinsulin may have some mild hypoglycemic action, C-peptide has no known physiologic function. Granules within the beta cells store the insulin in the form of crystals consisting of two atoms of zinc and six molecules of insulin. The entire human pancreas contains up to 8 mg of insulin, representing approximately 200 biologic units. Originally, the unit was defined on the basis of the hypoglycemic activity of insulin in rabbits. With improved purification techniques, the unit is presently defined on the basis of weight, and present insulin standards used for assay purposes contain 28 units per milligram.
Insulin is released from pancreatic beta cells at a low basal rate and at a much higher stimulated rate in response to a variety of stimuli, especially glucose. Other stimulants such as other sugars (eg, mannose), amino acids (especially gluconeogenic amino acids, eg, leucine, arginine), hormones such as glucagon-like polypeptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, cholecystokinin, high concentrations of fatty acids, and β-adrenergic sympathetic activity are recognized. Stimulatory drugs include sulfonylureas, meglitinide and nateglinide, isoproterenol, and acetylcholine. Inhibitory signals are hormones including insulin itself, islet amyloid polypeptide, somatostatin, and leptin; α-adrenergic sympathetic activity; chronically elevated glucose; and low concentrations of fatty acids. Inhibitory drugs include diazoxide, phenytoin, vinblastine, and colchicine.