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15.9: Pancreas

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    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).

    Pancreas
    The pancreatic exocrine function involves the acinar cells secreting digestive enzymes that are transported into the small intestine by the pancreatic duct. Its endocrine function involves the secretion of insulin (produced by beta cells) and glucagon (produced by alpha cells) within the pancreatic islets. These two hormones regulate the rate of glucose metabolism in the body. The micrograph reveals pancreatic islets. LM × 760. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

    This diagram shows the anatomy of the pancreas. The left, larger side of the pancreas is seated within the curve of the duodenum of the small intestine. The smaller, rightmost tip of the pancreas is located near the spleen. The splenic artery is seen travelling to the spleen, however, it has several branches connecting to the pancreas. An interior view of the pancreas shows that the pancreatic duct is a large tube running through the center of the pancreas. It branches throughout its length in to several horseshoe- shaped pockets of acinar cells. These cells secrete digestive enzymes, which travel down the bile duct and into the small intestine. There are also small pancreatic islets scattered throughout the pancreas. The pancreatic islets secrete the pancreatic hormones insulin and glucagon into the splenic artery. An inset micrograph shows that the pancreatic islets are small discs of tissue consisting of a thin, outer ring called the exocrine acinus, a thicker, inner ring of beta cells and a central circle of alpha cells.

    View the University of Michigan WebScope at 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.

    Homeostatic Regulation of Blood Glucose Levels
    Blood glucose concentration is tightly maintained between 70 mg/dL and 110 mg/dL. If blood glucose concentration rises above this range, insulin is released, which stimulates body cells to remove glucose from the blood. If blood glucose concentration drops below this range, glucagon is released, which stimulates body cells to release glucose into the blood.

    This diagram shows the homeostatic regulation of blood glucose levels. Blood glucose concentration is tightly maintained between 70 milligrams per deciliter and 110 milligrams per deciliter. If blood glucose concentration rises above this range (hyperglycemia), insulin is released from the pancreas. Insulin triggers body cells to take up glucose from the blood and utilize it in cellular respiration. Insulin also inhibits glycogenolysis, in that glucose is removed from the blood and stored as glycogen in the liver. Insulin also inhibits gluconeogenesis, in that amino acids and free glycerol are not converted to glucose in the ER. If blood glucose concentration drops below this range, glucagon is released, which stimulates body cells to release glucose into the blood. All of these actions cause blood glucose concentration to decrease. When blood glucose concentration is low (hypoglycemia), alpha cells of the pancreas release glucagon. Glucagon inhibits body cells from taking up glucose from the blood and utilizing it in cellular respiration. Glucagon also stimulates glycogenolysis, in that glycogen in the liver is broken down into glucose and released into the blood. Glucagon also stimulates glucogenogenesis, in that amino acids and free glycerol are converted to glucose in the ER and released into the blood. All of these actions cause blood glucose concentrations to increase.

    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

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