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The islets of Langerhans in the pancreas contain four main types of endocrine cells (Table 24–1). These cells include glucagon-producing alpha cells (A or α), insulin- and amylin-producing beta cells (B or β), somatostatin-producing delta cells (D or δ), and pancreatic polypeptide-producing cells (F). Of these, the insulin-producing B cells are the most numerous. The most common disease related to pancreatic function is diabetes mellitus (DM), a deficiency of insulin production or effect.

Table 24–1. Pancreatic Islet Cells and Their Secretory Products

Knowledge of the mechanism of action and physiologic function of insulin is critical in understanding the clinical use of insulin and oral hypoglycemic drugs as the pharmacologic treatments of DM.

Insulin is required in type 1 DM, and several parenteral formulations of insulin are available (Figure 24–1). Type 2 DM can be treated with drug classes that include four types of oral antidiabetic drugs, incretin mimetics, and an amylinomimetic (Figure 24–1), as well as insulin, if required. Glucagon, a hormone that affects the liver, cardiovascular system, and gastrointestinal tract, can be used to treat severe hypoglycemia in patients with DM.

Figure 24–1.

Drug classes used in the treatment of diabetes mellitus. Drug classes may be initially divided into insulin, amylinomimetics, incretin mimetics, and oral hypoglycemics. The oral hypoglycemics are subsequently divided into four classes based on mechanism of action.

Insulin is synthesized as proinsulin, an 86–amino acid single-chain polypeptide. Proinsulin is processed in the Golgi apparatus of pancreatic B cells and then packaged into granules in the form of crystals consisting of two atoms of zinc and six molecules of insulin. In the Golgi apparatus, cleavage of proinsulin removes a 31–amino acid C peptide and leaves two peptide chains that are then cross-linked by two disulfide bonds. Neither proinsulin nor C peptide appears to have important physiologic actions.

Insulin release from pancreatic B cells occurs at a low basal rate, and at a much higher rate in response to a variety of stimuli, especially glucose. The mechanism by which glucose regulates insulin release is well understood. In B cells, glucose metabolism increases intracellular adenosine triphosphate (ATP) levels. ATP-regulated potassium channels respond to increased ATP concentrations by closing, thus reducing potassium conductance (Figure 24–2...

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