Porth's Essentials of Pathophysiology, 4e

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Endocrine System

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class of drugs has been shown to reduce hyperglycemia in patients with diabetes. 5

glucagon, it is thought to extend the use of absorbed nutrients by the tissues. 2 Several gut-derived hormones have been identified as having what is termed an incretin effect, meaning that they increase insulin release after an oral nutri- ent load 2,3,6 (see Chapter 28). This suggests that gut- derived factors can stimulate insulin secretion after a predominantly carbohydrate meal. The two hormones that account for about 90% of the incretin effect are glucagon-like peptide-1, which is released from L cells in the distal small intestine, and glucose-dependent insu- linotropic polypeptide, which is released by K cells more proximally (mainly in the jejunum). Counterregulatory Hormones Other hormones that can affect blood glucose include the catecholamines, growth hormone, and the gluco- corticoids. These hormones, along with glucagon, are sometimes called counterregulatory hormones because they counteract the storage functions of insulin in reg- ulating blood glucose levels during periods of fasting, exercise, and other situations that either limit glucose intake or deplete glucose stores. Epinephrine. Epinephrine, a catecholamine, helps to maintain blood glucose levels during periods of stress. Epinephrine has the potent effect of stimulating glyco- genolysis in the liver, thus causing large quantities of glucose to be released into the blood. It also inhibits insulin release from the beta cells and thereby decreases the movement of glucose into muscle cells, while at the same time increasing the breakdown of muscle glycogen stores. Although the glucose that is released from muscle glycogen cannot be released into the blood, the mobi- lization of these stores for muscle use conserves blood glucose for use by other tissues such as the brain and nervous system. Epinephrine also has a direct lipolytic effect on adipose cells, thereby increasing the mobiliza- tion of fatty acids for use as an energy source. The blood glucose–elevating effect of epinephrine is an important homeostatic mechanism during periods of hypoglycemia. Growth Hormone. Growth hormone has many met- abolic effects. It increases protein synthesis in all cells of the body, mobilizes fatty acids from adipose tissue, and antagonizes the effects of insulin. Growth hormone decreases cellular uptake and use of glucose, thereby increasing the level of blood glucose. The increased blood glucose level stimulates further insulin secretion by the beta cells. The secretion of growth hormone normally is inhibited by insulin and increased levels of blood glucose. During periods of fasting, when both blood glucose levels and insulin secretion fall, growth hormone levels increase. Exercise, such as running and cycling, and various stresses, including anesthesia, fever, and trauma, also increase growth hormone levels. Chronic hypersecretion of growth hormone, such as occurs in acromegaly (see Chapter 32), can lead to glucose intolerance and the development of diabetes mellitus. In people who already have diabetes, moderate elevations in

Glucagon Glucagon, a polypeptide molecule produced by the alpha cells of the islets of Langerhans, helps to maintain blood glucose between meals and during periods of fasting. 2,3 Like insulin, glucagon travels through the portal vein to the liver, where it exerts its main action, which is to increase blood glucose (Table 33-1). The most dramatic effect of glucagon is its ability to initiate glycogenolysis (the breakdown of glycogen) as a means of raising blood glucose, usually within a matter of minutes. Glucagon also increases the transport of amino acids into the liver and stimulates their conversion into glucose through the process of gluconeogenesis. Because liver glycogen stores are limited, gluconeogenesis is important in maintaining blood glucose levels over time. Other actions of glucagon occur only when the hormone is present in high concen- trations, usually well above those normally present in the blood. At high concentrations, glucagon activates adipose cell lipase, making fatty acids available for use as energy. 2 Glucagon secretion is regulated by blood glucose. A decrease in blood glucose concentration produces an immediate increase in glucagon secretion, and an increase produces a decrease in glucagon secretion. High concentrations of amino acids, as occur after a protein meal, also can stimulate glucagon secretion. In this way, glucagon increases the conversion of amino acids to glu- cose as a means of maintaining the body’s glucose levels. Glucagon levels also increase during strenuous exercise as a means of preventing a decrease in blood glucose. Islet amyloid polypeptide, or amylin, was originally identified as a major constituent of pancreatic amyloid deposits in persons with type 2 diabetes and subsequently shown to be a polypeptide that is cosecreted with insu- lin from the beta cells in the pancreas. 3,5 Plasma levels of amylin increase in response to nutritional stimuli to produce inhibition of gastric emptying and glucagon secretion. As with insulin, the active form of amylin is derived from a larger proamylin precursor. Although the active form of amylin is soluble and acts as a hormone, there has been renewed interest in the less soluble and insoluble forms, which may cause degeneration of the beta cells and contribute to the pathogenesis of overt diabetes. 5 Somatostatin is a polypeptide hormone contain- ing only 14 amino acids that has an extremely short half-life. 2,3 Somatostatin secreted by the delta cells acts locally in the islets of Langerhans to inhibit the release of insulin and glucagon. It also decreases gastrointes- tinal activity after ingestion of food. Almost all fac- tors related to ingestion of food stimulate somatostatin secretion. By decreasing gastrointestinal activity, soma- tostatin is thought to extend the time during which food is absorbed into the blood, and by inhibiting insulin and Amylin, Somatostatin, and Gut-Derived Hormones