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Insulin

Insulin, a hormone, is used to regulate carbohydrate and fat metabolism in the body. Insulin causes cells to take up glucose from the blood and store it as glycogen in the liver and muscle. This hormone stops the body from using fat as an energy source by inhibiting the release of glucagons. Without insulin the body fails to take glucose into the bodies cells and in turns uses fat as an energy source. It also has several other anabolic effects throughout the body.

Diabetes mellitus results from insulin level control fails. That is why insulin is used to control diabetes. Type 1 diabetes patients need external insulin to survive because their bodies no longer produce it. Type 2 are resistant to insulin and can suffer from relative insulin deficiency. Insulin also influences other body functions like the vascular compliance and cognition and enhancing learning and memory as well as benefiting the verbal memory. It is also suggested that central nervous insulin contributes to the control of whole-body energy homeostasis in humans.

Composed of 51 amino acids, Insulin is a peptide hormone that has a molecular weight of 5808 Da. The Insulin’s structure varies slightly between each species of animal. Due to this variation insulin from animal sources differ somewhat in “strength” in humans. Porcine insulin is, however, close to the human version. Even insulin from some fish species is close enough to human to be clinically effective in humans. The C-peptide of proinsulin; however, differs much more amongst species.

There are several regulatory sequences in the promoter region of the human insulin gene, which transcription factors bind. There are also silencers that inhibit transcription.

Insulin, stored in the body as a hexamer, is active as a monomer. The hexamer has long-term stability which keeps the insulin protected, yet readily available. This hexamer-monomer conversion is a central aspect of insulin formulation for injection. The hexamer is more stable but the monomer is a faster reacting drug because diffusion rate is inversely related to particle size. Since the drugs can react quickly the injections don’t have to precede mealtimes by hours which allow diabetics to have more flexibility with their schedule.

The pancreas produces insulin that is released when certain stimuli including ingested protein and glucose in the blood produced from digested food. In carbohydrates there is a possibility to include glucose which will be absorbed into the bloodstream and the blood glucose level will begin to rise. Insulin initiates a signal transduction that increases glucose uptake and storage. Eventually the insulin is degraded and the response is terminated.

The pancreas is primarily an exocrine gland with one to three million islets of Langerhans that form the endocrine part. Only 2% of the total mass of the pancreas accounts for the endocrine portion. Within the islets of Langerhans the beta cells constitute 60-80% of all the cells. Within the beta cells insulin is synthesized from the proinsulin precursor molecule by the action of proteolytic enzymes known as prohormone convertases.

Insulin and its related proteins can also be produced inside the brain and when these protein levels are low there is a link to Alzheimer’s disease.

The Beta cells in the islets of Langerhans release insulin in phase one rapidly by a triggered response to increased blood glucose levels. The second phase is a steady, slow release of newly formed vesicles that are triggered independently of sugar.

Some insulin release takes place with food intake and the beta cells that release insulin can also be affected somewhat by the autonomic nervous system. However these signals are not fully understood.

Amino acids, acetylcholine, and gastrointestinal hormones are other substances that can stimulate insulin release. Three amino acids act similarly to glucose by altering the beta cell’s membrane potential. Adrenaline can also active the beta cells triggering insulin release.
Whenever glucose levels drop into normal physiologic value, the insulin release from the beta cells slows or stops. However, if blood glucose levels drop much lower than this the release of hyperglycemic hormones forces cellular stores to release glucose into the blood primarily from liver cell stores. The release of these hyperglycemic hormones prevents life-threatening hypoglycemia. Stress can be a major problem because it inhibits insulin release resulting in increased blood glucose levels during stress.

They are special transporter proteins in cell membranes through which glucose from the blood can enter a cell. Low levels of insulin prevent glucose from entering those cells.

Muscle cells and fat cells are most strongly influenced by insulin as far as stimulation of glucose uptake is concerned. They are important due to the muscle cells central role in movement, breathing, and circulation while the fat cells are important because they accumulate excess food energy against future needs. Together these cells make up about two-thirds of all cells in the human body.

The liver and kidney are responsible for the clearance of any used insulin. The liver does the primary work by clearing most insulin during first-pass transit while the kidney does the clearing primarily in the systemic circulation.

Lack of glucose can dramatically make itself manifest by impairing the central nervous system, causing dizziness, speech problems, and even loss of consciousness. This low glucose is known as hypoglycemia. There have actually been a few cases of murder and attempted murder by use of insulin overdose.

Synthetic “human” insulin is now manufactured for widespread clinical use. Researchers have even put the insulin gene into plants. Many of these are modified versions that have somewhat different absorption or duration of action characteristics. Insulin is taken through injections by needle or an insulin pump.

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Insulin


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