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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.
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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.
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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.
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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.
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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). Closure
of potassium channels results in membrane depolarization ...