Before the 1920s, diabetes mellitus* was a fatal disease, characterized by weakness, lethargy, and a dramatic loss of body mass. The disease was known to be connected somehow with the pancreas, a gland located just below the stomach (see Figure 42.2), and with abnormal glucose metabolism, but the link was not clear.
Today we know that diabetes mellitus is caused by a lack of the protein hormone insulin (type I or juvenile onset diabetes) or by a lack of insulin receptors on the target tissues (type II or adult onset diabetes). For patients in which the hormone is lacking, insulin replacement therapy is an extremely successful treatment. At present, more than 1.5 million people with diabetes in the United States lead almost normal lives through the use of manufactured insulin.
*The name diabetes refers to the copious production of urine. Mellitus (Greek for "honey") reflects the fact that the urine of an untreated diabetic is sweet.
Insulin binds to a receptor on the plasma membrane of a target cell, and this insulin-receptor complex allows glucose to enter the cell (see Figure 15.6). In the absence of insulin or insulin receptors, glucose fails to enter the cells, and instead accumulates in the blood until it is lost in the urine. High levels of blood glucose cause water to move from cells into the blood by osmosis, and the kidneys increase urine output to remove this excess fluid volume from the blood. Because glucose uptake by most cells is impaired without insulin, those cells must use fat and protein for fuel instead of glucose. As a result, the body of the untreated diabetic wastes away, and critical tissues and organs are damaged.
For centuries the prospects for a person with diabetes were bleak. A change in this outlook came almost overnight in 1921, when medical doctor Frederick Banting and medical student Charles Best of the University of Toronto discovered that they could reduce the symptoms of diabetes by injecting an extract they had prepared from pancreatic tissue. The active component of this extract was found to be a small protein hormone—insulin—consisting of 51 amino acids. For this discovery, Banting was awarded a Nobel prize, which he refused to accept because his student was not also honored.
Insulin is produced in clusters of endocrine cells in the pancreas. These clusters are called islets of Langerhans after the German medical student who discovered them. There are several types of cells in the islets:
► Beta (P) cells produce and secrete insulin.
► Alpha (a) cells produce and secrete the hormone gluca-gon, which has effects opposite from those of insulin.
► Delta (5) cells produce the hormone somatostatin.
The rest of the pancreas produces enzymes and other secretions that travel through ducts to the intestine, where they play roles in digestion.
After a meal, the concentration of glucose in the blood rises as glucose is absorbed from the food in the gut. This increase stimulates the P cells of the pancreas to release insulin. Insulin stimulates cells to use glucose as fuel and to convert it into storage products, such as glycogen and fat. When the gut contains no more food, the glucose concentration in the blood falls, and the pancreas stops releasing insulin. As a result, most cells of the body shift to using glycogen and fat, rather than glucose, for fuel. If the concentration of glucose in the blood falls substantially below normal, the islet a cells release glucagon, which stimulates the liver to convert glycogen back to glucose to resupply the blood. These actions will be discussed in greater detail in Chapter 50.
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