Overview of the Pancreas
The endocrine function of the pancreas is performed by small groups of cells, the islets of Langerhans, that are completely surrounded by acinar (exocrine) cells that produce digestive enzymes. The endocrine and exocrine portions of the pancreas are closely related during development, and evidence suggests that islet, acinar, and ductal cells arise from a common multipotential precursor cell.
Pancreatic islets contain α, β, and δ cells, each of which synthesize a unique polypeptide hormone. β cells account for 60%–70% of the islet-cell population and secrete insulin, α cells secrete glucagon, and δ cells secrete somatostatin.
The pancreatic islets function as discrete microendocrine organs. They are distributed throughout the pancreas with a characteristic pattern of cellular interrelationships to assure an appropriate balance of hormones. Afferent vessels and nerves enter the islet in the peripheral tricellular region. The close anatomic relationship of α, β, and δ cells in this heterogeneous cortical region allow it to function as a local glucose sensor, permitting a coordinated output of insulin and glucagon in response to fluctuations in blood glucose. Specialized tight junctions between membranes of adjacent endocrine cells tend to partition the intercellular space and may permit somatostatin to exert a direct local (paracrine) inhibitory effect on glucagon and insulin release.
Insulin is formed initially as a single polypeptide chain of 81–86 amino acid residues. This prohormone (proinsulin) contains the A and B chains of the insulin molecule, plus a connecting peptide. Proinsulin is converted enzymatically to insulin before storage in membrane-limited secretory granules.
The major physiologic stimulus for the release of insulin from β cells is an increase in the concentration of glucose in the extracellular fluid. Specific glucoreceptors that bind with glucose exist on the plasma membrane of β cells. An appropriate level of extracellular calcium is required for insulin secretion. Other sugars (fructose, mannose, ribose), amino acids (leucine, arginine), hormones (glucagon, secretin), drugs (sulfonylurea, theophylline), short-chain fatty acids, and ketone bodies may also stimulate insulin secretion under certain conditions. Pancreatic β cells are able to respond to a specific physiologic stimulus with release of stored hormone in a modulated fashion, rather than releasing all of the stored hormone at once.
Insulin affects, either directly or indirectly, the function of every organ in the body. Tissues that are especially responsive to insulin include skeletal and cardiac muscle, adipose tissue, fibroblasts, liver, WBCs, mammary glands, cartilage, bone, skin, aorta, pituitary gland, and peripheral nerves. The main function of insulin is to stimulate anabolic reactions involving carbohydrates, fats, proteins, and nucleic acids. Liver, adipose cells, and muscle are three principal target sites for insulin. Insulin catalyzes the formation of macromolecules used in cell structure and energy stores, and it regulates many cell functions. In general, insulin increases the transfer of glucose and certain other monosaccharides, some amino acids and fatty acids, and potassium and magnesium ions across the plasma membrane of target cells. It also decreases the rate of lipolysis, proteolysis, ketogenesis, and gluconeogenesis.
Glucagon is secreted in response to a reduction in blood glucose. It promotes mobilization of stores of energy-yielding nutrients by increasing glycogenolysis, gluconeogenesis, and lipolysis. At physiologic concentrations, glucagon increases both hepatic glycogenolysis and gluconeogenesis, thereby increasing blood glucose.
Insulin and glucagon act in concert to maintain the concentration of glucose in extracellular fluids within relatively narrow limits. A glucose sensor in the pancreatic islets controls the relative amounts of insulin and glucagon secreted. Glucagon controls glucose release from the liver into the extracellular space, and insulin controls glucose transport from the extracellular space into insulin-sensitive tissues such as fat, muscle, and liver.