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 |Favorite Table|Download (.pdf)
Table 24–1. Pancreatic
Islet Cells and Their Secretory Products
|Cell Types||Approximate Percentage of Islet Mass||Secretory Products|
|A cell (alpha)||20||Glucagon, proglucagon|
|B cell (beta)||75||Insulin, C peptide, proinsulin, amylin|
|D cell (delta)||3–5||Somatostatin|
|F cell (PP cell)1||<2||Pancreatic polypeptide|
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.
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). Closure
of potassium channels results in membrane depolarization ...