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Diabetes and Insulin

The failure to make insulin or insufficiency of insulin is termed as Diabetes mellitus. Insulin is a natural hormone which controls the level of the sugar glucose in the blood. Insulin allows cells to use glucose for energy. Cells cannot utilize glucose without insulin. Excess glucose builds up in the bloodstream, increasing the risk of diabetes. Glucose is the body's primary source of fuel. Insulin enables the body cells to take glucose from the bloodstream. The cells might use glucose for production of energy if required, or it is sent to the liver to preserve it, in the form of glycogen.
Functions of Insulin

In addition to its role of regulating glucose metabolism, insulin also

* Stimulates lipogenesis
* Diminishes lipolysis
* Increases amino acid transport into cells
* Modulates transcription
* Altering the cell content of numerous mRNAs
* Stimulates growth
* DNA synthesis
* Cell replication

Structure of Insulin

Insulin is composed of 2 peptide chains i.e. A chain and B chain. Both the chains are linked together by two disulfide bonds, and one disulfide is formed within the A chain. In most species, the A chain consists of 21 amino acids and the B chain of 30 amino acids that means it is composed of 51 amino acids in two peptide chains (A and B). The three-dimensional structure of insulin molecule (insulin monomer) exists in two main conformations. These differ in the extent of helix in the B chain due to phenol or its derivatives.

In acid solutions, the insulin monomer assembles as dimmers (diffuses in the blood) neutral pH and in the presence of zinc ions, as hexamers. The intermediate and long acting insulin has high proportion of hexamers, to delay its action. The sequence of amino acid in insulin varies among species, certain segments are conserved, like positions of the three disulfide bonds, both ends of the A chain and the C-terminal residues of the B chain. These similarities in the amino acid sequence of insulin lead to a three dimensional conformation of insulin that is very similar among species, and insulin from one animal is very likely biologically active in other species. Indeed, pig insulin has been widely used for human.

Structure of Insulin

The first of these molecules to be marketed - called insulin lispro - is engineered such that lysine and proline resting on the C-terminal end of the B chain are reversed; this modification does not alter receptor binding, but minimizes the tendency to form dimmers and hexamers.

Insulin Synthesis

Insulin is synthesized as a preprohormone in the beta cells of the islets of Langerhans. Its signal peptide is removed in the cisternae of the endoplasmic reticulum and then packaged into secretory vesicles in the Golgi. It is folded in its native structure and locked in this conformation by, the formation of 2 disulfide bonds.

In normal individual, insulin is produced by the body in response to the rise in blood glucose level. Apart from it, spurts of insulin are produced throughout the day and night, to look after the body resting needs for insulin and ensure that cells can take up glucose. In other words, function of insulin is to counter the concerted action of the numerous hyperglycemia generating hormones and to sustain low blood glucose levels. There are numerous hyperglycemic hormones untreated disorders associated with insulin, generally leading to severe hyperglycemia and a shortened life span.

In people with type 1 diabetes, the pancreas no longer release the insulin as the beta cells are destroyed and they need insulin shots to use glucose from meals. People with type 2 diabetes can produce insulin but, their body doesn't respond well to it. Some people with type 2 diabetes need diabetes pills or insulin dosages to utilize glucose for energy generation. Insulin cannot be taken as a pill as it will be break down during digestion just like the protein in food. Insulin must be injected into the fat under your skin, to make it get into your blood. By reducing the concentration of glucose in the blood, insulin is thought to prevent or reduce the long-term complications of diabetes, including damage to the blood vessels, eyes, kidneys, and nerves.

Types of Insulin

Good control of blood glucose levels is important for your health, now and in the future. Understanding your insulin treatment will help you to control diabetes. It will also help you to fit the diabetes into your life, instead of trying to fit your life around the diabetes.

There are more than 20 types of insulin products available in four basic forms, each with a different time of onset and duration of action. The decision as to which insulin to choose is based on an individual's lifestyle, blood sugar level and a physician's preference and experience. Criterions to be considered in choosing insulin are:

  • Onset:- how soon it starts working.
  • Peak time:- when it works the hardest.
  • Duration:- how long it lasts in the body.

Obesity affects the work of insulin in the body. If body has extra fat tissue, then it will be more resistant to insulin. Treatment for Type 1 diabetes most likely includes insulin via injections, inhaled insulin or an insulin pump. Your physician will recommend the appropriate insulin treatment and its delivery mechanism, in respect to individual case.

Insulin was prepared from bovine (beef) and porcine (pork) sources. Beef and pork insulin is no longer available in the United States. Instead, recombinant (human) insulin is used and marketed. Insulin can’t be taken by mouth because it would be destroyed by digestion, so it is administered subcutaneous by syringe. Since 1982, most of the newly approved insulin preparations have been produced by inserting portions of DNA ("recombinant DNA") into special lab-cultivated bacteria or yeast. This process allows the bacteria or yeast cells to produce complete human insulin. Recombinant human insulin has, for the most part, replaced animal-derived insulin, such as pork and beef insulin. Regular insulin acts within 30 minutes and its effect lasts for 6 to 8 hours. The maximal effect occurs 1 to 3 hours following the injection. As compared to regular insulin, insulin lispro acts more rapidly, has an earlier maximal effect and a shorter duration action. Therefore, insulin lispro should be given within 15 minutes of a meal, compared to regular insulin, which is given 30-60 minutes before meals.

Nowadays people with diabetes no longer need needles or shots to take insulin, as researchers have prepared new ways to get insulin into the bloodstream which can be just inhaled. In January 2006, the FDA approved inhaled insulin, started as a treatment option for Type 1 and Type 2 diabetes. This new type of insulin, available by the name Exubera, comes in powder form and is the first new insulin delivery option since the discovery of the hormone in the 1920s.


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