Insulin acts on the majority of tissues throughout the human body. However, the target tissues on which it has its most significant effects are fat tissue, skeletal muscle tissue, and liver tissue (1).
Receptors and their localization:
There has only been one type of receptor identified for insulin. The insulin receptor is a transmembrane protein that is embedded in the plasma membrane of its target cells. It
does not matter if the receptor is located in the muscle, liver, or fat, it still has the same structure and operates in the same manner. This receptor is composed of two alpha subunits and two beta subunits which are linked together by disulfide bonds. The alpha chains are completely extracellular and possess insulin binding domains which make them the portion of the receptor that actively binds insulin molecules. Meanwhile, the beta domains penetrate through the plasma membrane and into the cell where it is able to interact with other molecules within the cell (4).For instance, the beta subunits have tyrosine kinase activity. This means that the insulin receptor is able to function as an enzyme and phosphorylate itself as well as other target proteins. In order for this to occur, the receptor must first be activated by an insulin molecule. This activation starts with the alpha subunits which recognize and bind the insulin molecule. In turn, this causes the beta subunits to phosphorylate themselves which activates the catalytic activity of the receptor. Once activated, the insulin receptor is able to phosphorylate a number of intracellular proteins which in turn initiate the appropriate biological response within the specific target cell. In this case, the main function of the response is to reduce the amount of glucose in the blood when the concentrations are too high (4).
Function:
The primary function of insulin is to regulate blood glucose levels within the body to ensure that they are maintained at a relatively constant and stable level. Thus, like the majority of hormones, the purpose of insulin is to maintain some form of homeostasis within the body. In this case, it is blood glucose levels. As already mentioned, insulin’s specific role in mediating glucose concentrations in the blood is to ensure that they do not get too high (2).
For example, glucose is usually consumed by the body in its carbohydrate form suc
h as starch or sucrose. These carbohydrates travel through the digestive tract to the small intestine where they are hydrolyzed into individual glucose molecules. This glucose is then absorbed into the blood and transported throughout the body. This results in elevated concentrations of glucose in the blood which stimulates the release of insulin (2).The way in which the beta cells (body) are able to recognize these high blood sugar levels is that the plasma membranes of beta cells have special channels that serve as glucose detectors. When these “detectors” recognize that blood sugar levels are higher than normal, they signal the beta cells to release insulin into the blood stream. Once in the blood stream, insulin is able to return blood glucose to normal levels by initiating its various target tissues which reduce the amount of glucose in the blood stream. They are able to do this through a variety of mechanisms which initiate the uptake, storage, and utilization of glucose. In most cases, this is accomplished by converting soluble nutrients absorbed by the small intestine into their storable forms which are usually insoluble energy-rich products such as glycogen, protein, and fat (4).
Effects on Skeletal Muscle Tissue:
One of insulin’s many target tissues are skeletal muscle fibers. Here, it can either stimulate glucose uptake by activating glycogen synthesis. This involves converting glucose into glycogen through the glycogen synthase enzyme. Or, it can stimulate the uptake of amino acids and convert them into protein. Both actions result in the removal of glucose from the blood stream (2).
Effects on Liver Tissue:
Insulin also acts on liver cells where it triggers a variety of responses to remove glucose from the blood. Firstly, it can stimulate glycogen synthesis which causes the liver cells to uptake glucose and convert it into glycogen. Secondly, it can inhibit the production of the enzymes in liver cells which are involved in glycogen breakdown (glycogenolysis). Lastly, it is can inhibit gluconeogenesis which is responsible for converting fats and proteins into glucose. All of these actions result in less free glucose in the bloodstream (1).
Effects on Adipose Tissue:
Insulin also has a direct effect on adipose (fat) cells as it stimulates lipogenolysis. This results in the uptake of glucose from the blood in order to synthesize fat. At the same time, it also inhibits lipolysis which is the breakdown of triglycerides into fatty acids and glycerol which ultimately results in the production of glucose. Thus, both of these actions once again cause glucose to be removed from the bloodstream (2).
Effects on Hypothalamus:
Another one of the tissues that insulin acts on is the hypothalamus. Here, it reduces appetite which reduces the amount of glucose being ingested by the body (1).
Pathologies:
Type I (insulin-dependent) diabetes mellitus – This is a disease caused by a deficiency of insulin in the body. In turn, people with this disease suffer from severe hyperglycemia whic
h simply refers to high levels of glucose in the blood stream. This form of diabetes is due to the destruction of pancreatic beta cells within the body. The cause of this is usually due to the body having autoimmunity to one or more of the components of these cells. The onset of this disease generally occurs in childhood and it can be treated or controlled by insulin replacement therapy. This simply involves continuously injecting the individual with an alternate source of insulin. Some of the primary symptoms or side effects of this disease include a failure of the kidney to reclaim glucose so that glucose spills over into the urine causing it to smell and taste sweet. Similarly, there is also an increase in the volume of urine because of the osmotic effect of this glucose which reduces the return of water to the blood. In addition, if this disease is left untreated, it could even result in death. However, if tight control of blood glucose concentrations is maintained by monitoring, treatment with insulin and dietary management, it will minimize the long-term adverse effects of this disorder on blood vessels, nerves and other organ systems. Ultimately, this will allow the individual to live a healthy life (1).Type II (non-insulin-dependent) diabetes mellitus – This form of the diabetes disease is a result of insulin resistance, instead of a lack of insulin. In these patients, there is no initial deficiency in the amount of insulin in the body. The problem seems to lie in the target tissues inability to respond appropriately to insulin. In contrast to type I diabetes, the onset of this disease generally occurs in adulthood. The exact cause of the disease is unknown a
t this point, but recent research has shown that it may be due to an abnormality in the insulin receptor or defect in insulin signaling. In any event, the resistance to insulin that is observed in this disease also causes the individual to suffer from hyperglycemia. Thus, the side effects that are observed in this disease are very similar to those found in type I diabetes. Unfortunately, insulin injections do not work as a medication for this disease as there is no initial deficiency in insulin levels. Instead, drugs that contain hypoglycemic agents are administered through dietary therapy in order to treat this disease (1).Hyperinsulinemia (excessive insulin secretion) – This disease is actually the opposite of diabetes mellitus as it is a result of an over-secretion of insulin. It is typically caused by an insulin-secreting tumor which secretes insulin in concentrations much higher than normal. This results in high levels of insulin in the blood which causes an increase in the amount of glucose being removed from the blood through the insulin mediated pathways. In turn, there is a significant drop in blood glucose levels and the individual suffers from hypoglycemia. This causes the brain to become starved for energy and the body goes into what is known as “insulin shock”. Some of the symptoms and side effects of this are impaired functioning of the central nervous system which may include dizziness, speech problems, and even loss of consciousness. If left untreated this disease could be potentially life-threatening. Fortunately though, this condition is much less common than diabetes mellitus (4).
References:
1) http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pancreas.html
2)
http://en.wikipedia.org/wiki/Insulin
3)
http://www.endocrineweb.com/diabetes/2insulin.html
4) http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin_phys.html
5)
http://www.fda.gov/diabetes/insulin.html
