3-6-10. The Endocrine PancreasLearning Objectives
The
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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 IsletsThe pancreatic islets each contain four varieties of cells:
Regulation of Blood Glucose Levels by Insulin and GlucagonGlucose 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. GlucagonReceptors in the pancreas can sense the decline in blood glucose levels, such as during periods of fasting or during prolonged labor or exercise (Figure 2). In response, the alpha cells of the pancreas secrete the hormone
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. InsulinThe primary function of 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.
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Visit this link to view an animation describing the location and function of the pancreas. What goes wrong in the function of insulin in type 2 diabetes? 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. The pancreatic hormones are summarized in Table 1. Table 1. Hormones of the Pancreas
Disorders of the…Endocrine System: Diabetes MellitusDysfunction of insulin production and secretion, as well as the target cells’ responsiveness to insulin, can lead to a condition called There are two main forms of diabetes mellitus. Type 1 diabetes is an autoimmune disease affecting the beta cells of the pancreas. Certain genes are recognized to increase susceptibility. The beta cells of people with type 1 diabetes do not produce insulin; thus, synthetic insulin must be administered by injection or infusion. This form of diabetes accounts for less than five percent of all diabetes cases. Type 2 diabetes accounts for approximately 95 percent of all cases. It is acquired, and lifestyle factors such as poor diet, inactivity, and the presence of pre-diabetes greatly increase a person’s risk. About 80 to 90 percent of people with type 2 diabetes are overweight or obese. In type 2 diabetes, cells become resistant to the effects of insulin. In response, the pancreas increases its insulin secretion, but over time, the beta cells become exhausted. In many cases, type 2 diabetes can be reversed by moderate weight loss, regular physical activity, and consumption of a healthy diet; however, if blood glucose levels cannot be controlled, the diabetic will eventually require insulin. Two of the early manifestations of diabetes are excessive urination and excessive thirst. They demonstrate how the out-of-control levels of glucose in the blood affect kidney function. The kidneys are responsible for filtering glucose from the blood. Excessive blood glucose draws water into the urine, and as a result the person eliminates an abnormally large quantity of sweet urine. The use of body water to dilute the urine leaves the body dehydrated, and so the person is unusually and continually thirsty. The person may also experience persistent hunger because the body cells are unable to access the glucose in the bloodstream. Over time, persistently high levels of glucose in the blood injure tissues throughout the body, especially those of the blood vessels and nerves. Inflammation and injury of the lining of arteries lead to atherosclerosis and an increased risk of heart attack and stroke. Damage to the microscopic blood vessels of the kidney impairs kidney function and can lead to kidney failure. Damage to blood vessels that serve the eyes can lead to blindness. Blood vessel damage also reduces circulation to the limbs, whereas nerve damage leads to a loss of sensation, called neuropathy, particularly in the hands and feet. Together, these changes increase the risk of injury, infection, and tissue death (necrosis), contributing to a high rate of toe, foot, and lower leg amputations in people with diabetes. Uncontrolled diabetes can also lead to a dangerous form of metabolic acidosis called ketoacidosis. Deprived of glucose, cells increasingly rely on fat stores for fuel. However, in a glucose-deficient state, the liver is forced to use an alternative lipid metabolism pathway that results in the increased production of ketone bodies (or ketones), which are acidic. The build-up of ketones in the blood causes ketoacidosis, which—if left untreated—may lead to a life-threatening “diabetic coma.” Together, these complications make diabetes the seventh leading cause of death in the United States. Diabetes is diagnosed when lab tests reveal that blood glucose levels are higher than normal, a condition called
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Visit this link to view an animation describing the role of insulin and the pancreas in diabetes. Chapter ReviewThe pancreas has both exocrine and endocrine functions. The pancreatic islet cell types include alpha cells, which produce glucagon; beta cells, which produce insulin; delta cells, which produce somatostatin; and PP cells, which produce pancreatic polypeptide. Insulin and glucagon are involved in the regulation of glucose metabolism. Insulin is produced by the beta cells in response to high blood glucose levels. It enhances glucose uptake and utilization by target cells, as well as the storage of excess glucose for later use. Dysfunction of the production of insulin or target cell resistance to the effects of insulin causes diabetes mellitus, a disorder characterized by high blood glucose levels. The hormone glucagon is produced and secreted by the alpha cells of the pancreas in response to low blood glucose levels. Glucagon stimulates mechanisms that increase blood glucose levels, such as the catabolism of glycogen into glucose. Interactive Link QuestionsExercise 1Visit this link to view an animation describing the location and function of the pancreas. What goes wrong in the function of insulin in type 2 diabetes? Show/Hide Solution Insulin is overproduced. Review QuestionsExercise 2If an autoimmune disorder targets the alpha cells, production of which hormone would be directly affected?
Show/Hide Solution D Exercise 3Which of the following statements about insulin is true?
Show/Hide Solution SolutionB Critical Thinking QuestionsExercise 4What would be the physiological consequence of a disease that destroyed the beta cells of the pancreas? Show/Hide Solution The beta cells produce the hormone insulin, which is important in the regulation of blood glucose levels. All insulin-dependent cells of the body require insulin in order to take up glucose from the bloodstream. Destruction of the beta cells would result in an inability to produce and secrete insulin, leading to abnormally high blood glucose levels and the disease called type 1 diabetes mellitus. Exercise 5Why is foot care extremely important for people with diabetes mellitus? Show/Hide Solution Excessive blood glucose levels damage the blood vessels and nerves of the body’s extremities, increasing the risk for injury, infection, and tissue death. Loss of sensation to the feet means that a diabetic patient will not be able to feel foot trauma, such as from ill-fitting shoes. Even minor injuries commonly lead to infection, which , can progress to tissue death without proper care, requiring amputation. Glossaryalpha cell beta cell delta cell diabetes mellitus glucagon hyperglycemia insulin pancreas pancreatic islets PP cell
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