Insulin

In the early 1920’s Frederick Banting with the help of Charles Best was able to both discover and isolate a pure form of the hormone insulin. In fact, by the late 1920’s insulin was recognized as the first hormone ever discovered which earned Banting a Nobel Prize. Since then, many other hormones have been discovered which have all been determined to have their own specific roles in regulating different components of the human body. When combined, these hormones all work together to keep the body in homeostasis by responding to changes that may occur within the body or the surrounding environment. Upon recognizing a change (stimulus), the body is capable of releasing various hormones which initiate the appropriate response necessary to correct the change and bring the conditions within the body back to normal levels.

Insulin is one of many endocrine hormones found throughout the human body. An endocrine hormone is a chemical or protein (peptide) that is secreted by an endocrine tissue directly into the blood stream. Once it has entered the blood, the hormone is then carried by both blood and tissue fluids to the specific target cells that it acts upon. The specific endocrine tissues that secrete insulin are the bundles of cells found within the pancreas known as the islets of Langerhans. Even though the pancreas is mainly an exocrine gland, it contains millions of these islets which actually have an endocrine function. The islets of Langerhans are composed of four different types of cells including beta cells, alpha cells, delta cells, and gamma cells. However, it is only the beta cells that are capable of both synthesizing and secreting insulin.

It is within the beta cells that insulin is synthesized from its precursor molecule, proinsulin. The way in which this is accomplished is that inside a beta cell, proinsulin can be converted to insulin through the action of the proteolytic enzymes PC1 and PC2 (prohormone convertases) and the exoprotease, carboxypeptidase E. For instance, in the formation of insulin, the PC1 and PC2 enzymes remove the center portion (C-peptide) of the proinsulin molecule by cleaving it from the carboxyl and amino terminals of the polypeptide. The two remaining polypeptide chains, the alpha and beta chains are then bound together by disulfide bonds through the work of the carboxypeptidase E enzyme. The resulting molecule is the hormone known as insulin which can readily be secreted by the beta cells when it is needed by the body. In its final form, the insulin hormone that is secreted into the blood stream is a small protein (polypeptide) consisting of an alpha (21 amino acids) and beta (30 amino acids) chain. These two chains are connected by two disulfide bridges which yield a protein with a total of 51 amino acids.

The main function of insulin is to regulate carbohydrate metabolism within the body. More specifically, it regulates the levels of glucose in the blood as all sugars are converted to some form of glucose upon entering the body. Insulin’s role in regulating blood glucose levels is to ensure that they do not get too high. Thus, insulin is secreted by the beta cells in a normal person when the body recognizes that there are high levels of glucose in the blood. The way in which the beta cells (body) is able to recognize high blood sugar levels is that the plasma membrane 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 several responses in the body which aid in removing glucose from the blood. It does this by acting on many of the bodies organs which all remove glucose from the blood in a similar fashion.

For instance, one of insulin’s many target tissues are skeletal muscle fibers. Here, it can either stimulate the uptake of glucose and convert it into glycogen or stimulate the uptake of amino acids and convert them into protein. Both actions result in the removal of glucose form the blood stream. At the same time, insulin also acts on liver cells where it triggers a variety of responses to remove glucose from the blood. Firstly, it can stimulate 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. Next, insulin also has a direct effect on adipose (fat) cells where it stimulates the uptake of glucose in order to synthesize fat. Meanwhile, the final tissue that insulin acts on is the hypothalamus where it reduces appetite which reduces the amount of glucose ingested by the body.

The way in which insulin is able to trigger such responses at all of these sites is that all of the target tissues contain insulin receptors. These are generally transmembrane proteins that are embedded in the plasma membrane of the responding cells. These receptors are capable of both recognizing and binding insulin. Once insulin binds to its receptor, it creates a hormone-receptor complex which initiates the appropriate response in each of the target tissues. In this case, all of the actions induced by insulin are very efficient means of lowering blood glucose levels. In most cases, it does this 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.

References:

http://nobelprize.org/nobel_prizes/medicine/laureates/1923/banting-bio.html
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pancreas.html
http://en.wikipedia.org/wiki/Insulin
http://www.discoveryofinsulin.com/Home.htm
http://www.endocrineweb.com/diabetes/2insulin.html