The pancreas is a long organ that lies transversely in the abdomen between the kidneys and near the duodenum of the small intestine. It is composed of two types of tissue. Exocrine tissue produces and secretes digestive juices that go by way of ducts to the small intestine. Endocrine tissue, called the pancreatic islets (islets of Langerhans), produces and secretes the hormones insulin and glucagon directly into the blood (Fig. 10.12).
     The two antagonistic hormones insulin and glucagon, both produced by the pancreas, help maintain the normal level of glucose in the blood. Insulin is secreted when the blood glucose level is high, which usually occurs just after eating. Insulin stimulates the uptake of glucose by cells, especially liver cells, muscle cells, and adipose tissue cells. In liver and muscle cells, glucose is then stored as glycogen. In muscle cells, the glucose supplies energy for muscle contraction, and in fat cells, glucose enters the metabolic pool and thereby supplies glycerol for the formation of fat. In these ways, insulin lowers the blood glucose level. Individuals who do not produce insulin have a condition called diabetes mellitus type I.
     Glucagon is secreted from the pancreas, usually between meals, when the blood glucose level is low. The major target tissues of glucagon are the liver and adipose tissue. Glucagon stimulates the liver to break down glycogen to glucose and to use fat and protein in preference to glucose as energy sources. Adipose tissue cells break down fat to glycerol and fatty acids. The liver takes these up and uses them as substrates for glucose formation. In these ways, glucagon raises the blood glucose level.
Figure 10.12 Regulation of blood glucose level. Top: When the blood glucose level is high, the pancreas secretes insulin. Insulin promotes the storage of glucose as glycogen in the liver and muscles and the use of glucose to form fat in adipose tissue. Therefore, insulin lowers the blood glucose level. Bottom: When the blood glucose level is low, the pancreas secretes glucagon. Glucagon acts opposite to insulin; therefore, glucagon raises the blood glucose level to normal.
Regulation of blood glucose level
Diabetes Mellitus
     Diabetes mellitus is a fairly common hormonal disease in which liver cells, and indeed all body cells, are unable to take up and / or metabolize glucose. Therefore, the blood glucose level is elevated, called hyperglycemia, and the person becomes extremely hungry, called polyphagia. As the blood glucose level rises, glucose and water are excreted in excess, called glycosuria and polyuria, respectively. The loss of water in this way causes the diabetic to be extremely thirsty, called polydipsia. Since glucose is not being metabolized, the body turns to the breakdown of protein and fat for energy.
     We now know that diabetes mellitus exists in two forms. In type I, more often called insulin-dependent diabetes mellitus (IDDM), the pancreas is not producing insulin. This condition is believed to be brought on, at least in part, by exposure to an environmental agent, most likely a virus, whose presence causes immune cells to destroy the pancreatic islets. The body turns to the metabolism of fat, which leads to the buildup of ketones in the blood, called ketonuria, and in turn to acidosis (acid blood), which can lead to coma and death. As a result, the individual must have daily insulin injections. These injections control the diabetic symptoms but can still cause inconveniences, because either an overdose of insulin or missing a meal can bring on the symptoms of hypoglycemia (low blood sugar). These symptoms include perspiration, pale skin, shallow breathing, and anxiety. The cure is quite simple: Immediate ingestion of a sugar cube or fruit juice can very quickly counteract hypoglycemia.
      Of the 16 million people who now have diabetes in the United States, most have type II, more often called non insulin dependent diabetes (NIDDM). This type of diabetes mellitus usually occurs in people of any age who tend to be obese- adipose tissue produces a substance that interferes with the transport of glucose into cells.
The amount of insulin in the blood is normal or elevated, but the insulin receptors on the cells do not respond to it. It is possible to prevent, or at least control, type II diabetes by adhering to a low-fat, lowsugar diet and exercising regularly. If this fails, oral drugs that stimulate the pancreas to secrete more insulin and enhance the metabolism of glucose in the liver and muscle cells are available. It’s projected that as many as 7 million Americans may have type II diabetes without being aware of it. Yet, the effects of untreated type II diabetes are as serious as those of type I diabetes.
     Long-term complications of both types of diabetes are blindness, kidney disease, and circulatory disorders, including atherosclerosis, heart disease, stroke, and reduced circulation. The latter can lead to gangrene in the arms and legs. Pregnancy carries an increased risk of diabetic coma, and the child of a diabetic is somewhat more likely to be stillborn or to die shortly after birth. However, these complications of diabetes are not expected to appear if the mother’s blood glucose level is carefully regulated and kept within normal limits during the pregnancy.
Pancreatic Islet Cell Transplants
“I can remember getting sick with the flu just before I was diagnosed. I was eleven, and I was sick enough to miss two or three days of school. Then I just never got my strength back. I ate and drank constantly because I was thirsty and hungry all the time. I was always in the bathroom. It was so embarrassing. I started wetting the bed-can you imagine, at age 11? I fell asleep in school, and the teacher could barely get me to wake up. That’s when my doctor diagnosed my diabetes for the first time.”
     The patient, age 25, is a typical type I, juvenile-onset or insulin-dependent diabetic. Her symptoms are classic for insulindependent diabetes mellitus (IDDM).
     In insulin-dependent diabetes, the insulin-producing islet cells of the pancreas have been destroyed. Researchers think this is due to a malfunction of the immune system that causes the body’s own immune cells to target the pancreas. Thus, insulindependent diabetes is considered an autoimmune disease. As the name suggests, insulin must be taken by injection. The diabetic patient’s life then revolves around two to three daily insulin injections or monitoring by an insulin pump device that injects insulin automatically. Four or more daily blood tests are used to check blood glucose levels, and the patient must also monitor diet, activity level, exercise, and stress.
     “My insulin pump saves me from those three-a-day shots, but boy, do I hate finger sticks to test my blood,” the patient says with a wistful smile. “I know how carefully I have to manage this disease. Diabetics lose their sight, or go into kidney failure, or wind up having an early heart attack or stroke. I wish I could be placed on a transplant list for a pancreas, but everybody wants a pancreas. There aren’t enough human donors to go around.”
     Pancreatic transplantation has been available to IDDM sufferers since 1966, but it suffers from the same limitations of all transplant technology. Transplanting an entire organ is major surgery, and there is always a shortage of available donors. Strong drugs must be taken for the rest of the patient’s life in order to suppress the immune system. These antirejection drugs can have toxic effects on normal body cells. Moreover, with a weakened immune system, the patient has an increased risk of developing lifethreatening infections or cancer.
     The technique of pancreatic islet cell transplantation seems to hold promise for solving the problems of the traditional pancreas transplant. The islet cells are first isolated from a donor pancreas. The cells are then directly injected through the hepatic portal vein into the liver, where they form colonies and begin to produce insulin. This technique is much simpler than whole-pancreas transplantation and does not involve major surgery. In clinical studies, islet cells have been successfully implanted into human volunteers, who were then able to stop insulin injections.
Figure 10A Encapsulated insulin-producing pancreatic islet cells from pigs can be transplanted into patients without the need for immune systemsuppressing drugs.
Encapsulated insulin
     It is estimated that 700,000 islets will be needed to produce enough insulin for an adult. Several donor pancreases are needed to harvest sufficient islet cells for a single transplant. If an animal cell source could be used, unlimited islet cells would be available. Heart valves from pigs have been used for decades, and insulin for injection into humans was first isolated from pigs. Tissue engineers are now experimenting with islet cells from pigs. These islet cells have been isolated and surrounded by a semipermeable plastic membrane, a process called microencapsulation. These capsules are so small that they can be placed into the abdomen, where they will float freely and produce insulin as needed (Fig. 10A). The membrane of the capsule contains pores large enough to allow oxygen and nutrients to flow in and wastes and insulin to flow out by diffusion. But the membrane prevents immune cells from coming into contact with the enclosed pancreatic cells. Unless immune cells actually come in contact with transplanted cells, they cannot destroy them. Therefore, the patient does not need to take harsh antirejection drugs, and the immune system can function normally to suppress infection and cancer. Researchers are optimistic that prepared microencapsulated islet cells could soon be available for clinical trials.
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