99 Pancreas
The pancreas is a long, slender organ, most of which is located posterior to the bottom half of the stomach. Although it is primarily an exocrine gland, secreting a variety of digestive enzymes, the pancreas has an endocrine function. Its pancreatic islets—clusters of cells formerly known as the islets of Langerhans—secrete the hormones glucagon, insulin, somatostatin, and pancreatic polypeptide (PP).
View the University of Michigan WebScope at http://141.214.65.171/Histology/Digestive%20System/Liver%20and%20Pancreas/188B_HISTO_40X.svs/view.apml to explore the tissue sample in greater detail.
Cells and Secretions of the Pancreatic Islets
The pancreatic islets each contain four varieties of cells:
- The alpha cell produces the hormone glucagon and makes up approximately 20 percent of each islet. Glucagon plays an important role in blood glucose regulation; low blood glucose levels stimulate its release.
- The beta cell produces the hormone insulin and makes up approximately 75 percent of each islet. Elevated blood glucose levels stimulate the release of insulin.
- The delta cell accounts for four percent of the islet cells and secretes the peptide hormone somatostatin. Recall that somatostatin is also released by the hypothalamus (as GHIH), and the stomach and intestines also secrete it. An inhibiting hormone, pancreatic somatostatin inhibits the release of both glucagon and insulin.
- The PP cell accounts for about one percent of islet cells and secretes the pancreatic polypeptide hormone. It is thought to play a role in appetite, as well as in the regulation of pancreatic exocrine and endocrine secretions. Pancreatic polypeptide released following a meal may reduce further food consumption; however, it is also released in response to fasting.
Regulation of Blood Glucose Levels by Insulin and Glucagon
Glucose is required for cellular respiration and is the preferred fuel for all body cells. The body derives glucose from the breakdown of the carbohydrate-containing foods and drinks we consume. Glucose not immediately taken up by cells for fuel can be stored by the liver and muscles as glycogen, or converted to triglycerides and stored in the adipose tissue. Hormones regulate both the storage and the utilization of glucose as required. Receptors located in the pancreas sense blood glucose levels, and subsequently the pancreatic cells secrete glucagon or insulin to maintain normal levels.
Glucagon
Receptors in the pancreas can sense the decline in blood glucose levels, such as during periods of fasting or during prolonged labor or exercise. In response, the alpha cells of the pancreas secrete the hormone glucagon, which has several effects:
- It stimulates the liver to convert its stores of glycogen back into glucose. This response is known as glycogenolysis. The glucose is then released into the circulation for use by body cells.
- It stimulates the liver to take up amino acids from the blood and convert them into glucose. This response is known as gluconeogenesis.
- It stimulates lipolysis, the breakdown of stored triglycerides into free fatty acids and glycerol. Some of the free glycerol released into the bloodstream travels to the liver, which converts it into glucose. This is also a form of gluconeogenesis.
Taken together, these actions increase blood glucose levels. The activity of glucagon is regulated through a negative feedback mechanism; rising blood glucose levels inhibit further glucagon production and secretion.
Insulin
The primary function of insulin is to facilitate the uptake of glucose into body cells. Red blood cells, as well as cells of the brain, liver, kidneys, and the lining of the small intestine, do not have insulin receptors on their cell membranes and do not require insulin for glucose uptake. Although all other body cells do require insulin if they are to take glucose from the bloodstream, skeletal muscle cells and adipose cells are the primary targets of insulin.
The presence of food in the intestine triggers the release of gastrointestinal tract hormones such as glucose-dependent insulinotropic peptide (previously known as gastric inhibitory peptide). This is in turn the initial trigger for insulin production and secretion by the beta cells of the pancreas. Once nutrient absorption occurs, the resulting surge in blood glucose levels further stimulates insulin secretion.
Precisely how insulin facilitates glucose uptake is not entirely clear. However, insulin appears to activate a tyrosine kinase receptor, triggering the phosphorylation of many substrates within the cell. These multiple biochemical reactions converge to support the movement of intracellular vesicles containing facilitative glucose transporters to the cell membrane. In the absence of insulin, these transport proteins are normally recycled slowly between the cell membrane and cell interior. Insulin triggers the rapid movement of a pool of glucose transporter vesicles to the cell membrane, where they fuse and expose the glucose transporters to the extracellular fluid. The transporters then move glucose by facilitated diffusion into the cell interior.
Insulin also reduces blood glucose levels by stimulating glycolysis, the metabolism of glucose for generation of ATP. Moreover, it stimulates the liver to convert excess glucose into glycogen for storage, and it inhibits enzymes involved in glycogenolysis and gluconeogenesis. Finally, insulin promotes triglyceride and protein synthesis. The secretion of insulin is regulated through a negative feedback mechanism. As blood glucose levels decrease, further insulin release is inhibited.
| Hormones of the Pancreas | ||
|---|---|---|
| Associated hormones | Chemical class | Effect |
| Insulin (beta cells) | Protein | Reduces blood glucose levels |
| Glucagon (alpha cells) | Protein | Increases blood glucose levels |
| Somatostatin (delta cells) | Protein | Inhibits insulin and glucagon release |
| Pancreatic polypeptide (PP cells) | Protein | Role in appetite |