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| Link to graphic showing the location of the pancreas and other endocrine glands (92K). |
Insulin affects many organs. It
In each case, insulin triggers these effects by binding to the insulin receptor — a transmembrane protein embedded in the plasma membrane of the responding cells.
Taken together, all of these actions result in:| Diabetes mellitus is a disorder quite distinct from the similarly-named diabetes insipidus. They both result in the production of large amounts of urine (diabetes), but in one the urine is sweet while in the other (caused by ADH deficiency) it is not. Before the days of laboratory tests, a simple taste test ("mellitus" or "insipidus") enabled the doctor to make the correct diagnosis. |
IDDM is controlled by carefully-regulated injections of insulin. (Insulin cannot be taken by mouth because, being a protein, it would be digested.)
For many years, insulin extracted from the glands of cows and pigs was used. However, pig insulin differs from human insulin by one amino acid; beef insulin by three. Although both work in humans to lower blood sugar, they are seen by the immune system as "foreign" and induce an antibody response in the patient that blunts their effect and requires higher doses.
Two approaches have been taken to solve this problem:
Injections of insulin must be done carefully. Injections after vigorous exercise or long after a meal may drive the blood sugar level down to a dangerously low value causing an insulin reaction. The patient becomes irritable, fatigued, and may lose consciousness. If the patient is still conscious, giving a source of sugar (e.g., candy) by mouth usually solves the problem quickly. Injections of glucagon are sometimes used.
Many people develop diabetes mellitus without an accompanying drop in insulin levels (at least at first).
In many cases, the problem appears to be a failure to express a sufficient number of glucose transporters in the plasma membrane (and T-system) of their skeletal muscles.
Normally when insulin binds to its receptor on the cell surface, it initiates a chain of events that leads to the insertion in the plasma membrane of increased numbers of a transmembrane glucose transporter.| Discussion of how transmembrane proteins are moved to the surface of the cell in which they are synthesized. |
This transporter forms a channel that permits the facilitated diffusion of glucose into the cell.
Skeletal muscle is the major "sink" for removing excess glucose from the blood (and converting it into glycogen). In NIDDM, the patient's ability to remove glucose from the blood and convert it into glycogen may be only 20% of normal. This is called insulin resistance. Curiously, vigorous exercise seems to increase the expression of the glucose transporter (called GLUT-4) on skeletal muscle and this may explain why IDDM is more common in people who live sedentary lives.
NIDDM (also called Type 2 diabetes mellitus) usually strikes in adults and, particularly often, in overweight people. However, over the last few years in the U. S., the incidence of NIDDM in children has grown to the point where they now account for 20% of all newly-diagnosed cases (and, like their adult counterparts, are usually overweight).
Several drugs, all of which can be taken by mouth, are useful in restoring better control over blood sugar in patients with NIDDM.
However, late in the course of disease, patients may have to begin to take insulin. It is as though after years of pumping out insulin in an effort to overcome the patient's insulin resistance, the beta cells become exhausted.
Amylin is a peptide of 37 amino acids, which is also secreted by the beta cells of the pancreas.
Some of its actions:
The alpha cells of the islets secrete glucagon, a polypeptide of 29 amino acids.
Glucagon acts principally on the liver where it stimulates the conversion of glycogen into glucose ("glycogenolysis") which is deposited in the blood.
Glucagon secretion is
The physiological significance of this is that glucagon functions to maintain a steady level of blood sugar level between meals.
Injections of glucagon are sometimes given to diabetics suffering from an insulin reaction in order to speed the return of normal levels of blood sugar.
The delta cells secrete somatostatin. This consists of two polypeptides, one of 14 amino acids and one of 28.
Somatostatin has a variety of functions. Taken together, they work to reduce the rate at which food is absorbed from the contents of the intestine.
Somatostatin is also secreted by the hypothalamus and by the intestine. Further information about somatostatin can be found by following the links.
The gamma cells of the islets secrete a 36-amino-acid pancreatic polypeptide, which reduces appetite.
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