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Insulin quick review
Hormone description: a natural hormone synthesized within the beta cells of the islets of Langerhans in the pancreas.
Biological functions: stimulates the formation of glycogen in the muscles and in the liver, and suppresses gluconeogenesis by the liver.

Health benefits: promotes the cellular uptake of blood glucose to lower the blood glucose concentration, increases protein synthesis in muscle.
Insulin administration: usually taken as subcutaneous injections by syringes with needles, by insulin pens with needles, or by insulin pumps.


Insulin is a natural hormone made by the pancreas that controls the level of the sugar glucose in the blood. Insulin is synthesized in humans and other mammals within the beta cells (B-cells) of the islets of Langerhans in the pancreas. Insulin is derived from
proinsulin by cleavage of the C-peptide structure at the dipeptides Arg-Arg and Lys-Arg. Insulin is composed of an A chain of 21 amino acids and a B chain of 30 amino acids, the chains being held together by two disulfide bonds. Insulin is available from bovine (beef), porcine (pork), and recombinant (human) sources. Beef insulin differs from human insulin in two amino acid residues, and pork insulin in one residue. Fish insulin is also close enough to human insulin to be effective. In humans, insulin has a molecular weight of 5734. Regular (rapid onset, short-acting) and NPH (slower onset, longer duration) human insulin are the most commonly-used preparations.

Insulin plays a major part in the uptake of glucose by the cells of the body. It stimulates the formation of glycogen in the muscles and in the liver, while suppressing gluconeogenesis by the liver. When glucose enters our blood, the pancreas should automatically produce the right amount of insulin to move glucose into our cells. People with type 1 diabetes produce no insulin. People with type 2 diabetes do not always produce enough insulin. Glucose is normally the only sugar found in the blood. Blood glucose concentrations are kept within a relatively narrow range by such factors as hepatic and renal uptake and release, glucose removal by peripheral tissues, hormone influences on uptake and release, and intestinal absorption. Digestion causes carbohydrates to break down into glucose. After digestion, glucose is carried in the blood and goes to body cells where it is used for energy or stored. Insulin helps the body utilize blood glucose (blood sugar) by binding with receptors on cells like a key would fit into a lock. Once the key insulin- has unlocked the door, the glucose can pass from the blood into the cell. Inside the cell, glucose is either used for energy or stored for future use in the form of glycogen in liver or muscle cells.


Actions and functions of insulin

Insulin acts to promote the cellular uptake of blood glucose and, therefore, to lower the blood glucose concentration. The major function of insulin is to counter the concerted action of a number of hyperglycemia-generating hormones and to maintain low blood glucose levels. Insulin stimulates lipogenesis, diminishes lipolysis, and increases amino acid transport into cells. Insulin also
modulates transcription, altering the cell content of numerous mRNAs. It stimulates growth, DNA synthesis, and cell replication, effects that it holds in common with the insulin-like growth factors (IGFs) and relaxin. Insulin acts to reduce extracellular (including blood plasma) levels of glucose by interacting in some way yet unknown with various cell membranes.

Insulin induces its effects by binding to specific tyrosine kinase receptors in the plasma membrane of its target cells. Insulin stimulates the synthesis of glycogen by triggering a pathway that dephosphorylates glycogen synthase. The dephosphorylation activates the synthase. This also leads to the dephosphorylation of phosphorylase kinase, an enzyme needed in the breakdown of glucose. In adipose (fatty) tissue it facilitates the cellular uptake of glucose and its subsequent conversion to fatty acids, and it inhibits the breakdown of fatty acids to simpler compounds. In muscle insulin facilitates the transport of glucose into cells and in addition stimulates its conversion to glycogen. Insulin also increases protein synthesis in muscle. In the liver, insulin facilitates glucose catabolism and its conversion to glycogen and inhibits its synthesis from simpler compounds.

Insulin is used medically in some forms of diabetes mellitus. Patients with Type 1 diabetes mellitus depend on exogenous insulin (injected subcutaneously) for their survival because of an absolute deficiency of the hormone; patients with Type 2 diabetes mellitus have either relatively low insulin production or insulin resistance, and occasionally require insulin administration if other medications are inadequate in controlling blood glucose levels. Insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen, lowered levels of insulin cause liver cells to convert glycogen to glucose and excrete it into the blood. This is the clinical action of insulin which is useful in reducing high blood glucose levels in diabetes.


Insulin resistance syndrome

Insulin resistance syndrome, or Syndrome X, is a condition where muscle cells have lost insulin sensitivity to the point that glucose no longer enters them. This causes more insulin to be released by the pancreas, resulting in an excess amount of insulin circulating in the blood and often a craving for more food. Insulin resistance is a decreased ability to use insulin to transport glucose into the body’s cells where it is needed for energy production. Insulin resistance can be linked to diabetes, hypertension, dyslipidemia, cardiovascular disease and other abnormalities. These abnormalities constitute the insulin resistance syndrome. Insulin resistance syndrome is caused by elevated insulin levels due to high blood pressure, high triglycerides and low HDL, excessive fat tissue in the abdominal region or a family history of diabetes. Insulin resistance occurs when the normal amount of insulin secreted by the pancreas is not able to unlock the door to cells. To maintain a normal blood glucose, the pancreas secretes additional insulin. In some cases (about 1/3 of the people with insulin resistance), when the body cells resist or do not respond to even high levels of insulin, glucose builds up in the blood resulting in high blood glucose or type 2 diabetes. Even people with diabetes who take oral medication or require insulin injections to control their blood glucose levels can have higher than normal blood insulin levels due to insulin resistance.


Insulin and diabetes mellitus

Diabetes is a disease that occurs when the body is either unable to produce insulin or to use it properly. Diabetes mellitus is characterized by varying or persistent hyperglycemia (elevated blood sugar levels), especially after eating. All types of diabetes mellitus share similar symptoms and complications at advanced stages. Hyperglycemia itself can lead to dehydration and ketoacidosis. The most important forms of diabetes are due to decreased production of insulin (diabetes mellitus type 1), or decreased sensitivity of body tissues to insulin (diabetes mellitus type 2, the more common form). Type I, which is genetic, is caused by an autoimmune response of the white blood cells to destroy the beta cells of the pancreas. The only treatment available for this type of diabetes is insulin injections. Type II diabetes is much more common and does not require the injection of insulin. It is usually caused by too high an insulin concentration in the blood stream. This is caused by the target cells' hyporesponsiveness to insulin. Type 1 diabetes most often manifests in childhood (hence also called juvenile onset diabetes) and is the result of an autoimmune destruction of the b-cells of the pancreas. Non-insulin-dependent diabetes mellitus (NIDDM or type 2 diabetes) is characterized by persistent hyperglycemia but rarely leads to ketoacidosis. Type 2 diabetes generally manifests after age 40 and therefore has the obselete name of adult onset-type diabetes. Type 2 diabetes can result from genetics defects that cause both insulin resistance and insulin deficiency.


Modes of insulin administration, types of insulin delivery devices

Unlike many medicines, insulin cannot be taken orally. It is treated in the gastrointestinal tract precisely as any other protein. It cannot be swallowed, because digestive enzymes would destroy the insulin before it reached the bloodstream. Insulin is usually taken as subcutaneous injections by single-use syringes with needles, or by repeated-use insulin pens with needles.

Syringes - Syringes are hypodermic needles attached to hollow barrels that people with diabetes use to inject insulin. Insulin syringes are small with very sharp points. Most have a special coating to help the needles enter the skin as painlessly as possible. Insulin syringes come in several different sizes to match insulin strength and dosage.

Insulin pens - Insulin pen is an insulin injection device the size of a pen that includes a needle and holds a vial of insulin. It can be used instead of syringes for giving insulin injections. Some pens use replaceable cartridges of insulin; other models are totally disposable after the pre-filled cartridge is empty. A fine short needle, like the needle on an insulin syringe, is on the tip of the pen. Users turn a dial to select the desired dose of insulin and press a plunger on the end to deliver the insulin just under the skin.

Insulin pump - Insulin pump is a portable, battery-operated device that delivers a specific amount of insulin through the abdominal wall. It can be programmed to deliver different doses at different times of the day, according to the body's needs. The pump is worn outside the body, usually attached to a belt or waistband. Insulin is pumped from a reservoir through a catheter inserted under the skin of the abdominal wall. The insulin is delivered in a steady, measured dose through a system of plastic tubing (infusion set). Most infusion sets are started with a guide needle, then the plastic cannula (a tiny, flexible plastic tube) is left in place, taped with dressing, and the needle is removed.