Sandbox Reserved 1332

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This Sandbox is Reserved from January through July 31, 2018 for use in the course HLSC322: Principles of Genetics and Genomics taught by Genevieve Houston-Ludlam at the University of Maryland, College Park, USA. This reservation includes Sandbox Reserved 1311 through Sandbox Reserved 1430.

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1 Human Insulin - Structural Highlights
2 Function
3 Genetic and Historical Relevance
4 Diseases
5 References

Human Insulin - Structural Highlights

Insulin is made up of two peptide chains: the and the

There are several disulfide bonds that hold the molecule together and this general amino acid sequence and structure doesn't vary much from species to species. This is the reason why pig insulin was once produced for human use. Hydrophobic regions are clustered at the center which contributes to protein stability along with the disulfide bridges.

When insulin is being produced in the ER of beta cells, proinsulin is cleaved in two places creating the A and B chains of insulin and an inactive C peptide in the middle.

Insulin molecules often form dimers or in solution because of hydrogen bonding between molecules. This has clinical significance as monomers and dimers of insulin are more readily accepted into the bloodstream than hexamers are. Hexamers would take longer to diffuse and could be detrimental to the immediate sugar needs of diabetics.

Function

Insulin has a wide variety of functions the most basic of which is regulation of how the body uses and stores glucose and fat. Many of the body's cells rely on insulin to take glucose from the blood for energy. Insulin helps control blood glucose levels and prevent hyperglycemia, a condition with too much glucose in the blood stream. Insulin encourages the storage of glucose as glycogen in the liver, muscle, and fat cells and decreases the amount of glucose in the blood stream returning levels to normal.

Insulin is produced in the beta cells in the Islets of Langerhans in the pancreas and is released into the bloodstream when we eat. It operates by binding to the Insulin Receptor Protein on the surface of the cell, activating the glucose transporter molecules to allow glucose to move into the cell by a signal transduction cascade involving phosphorylation. When something like insulin resistance occurs, cells don't respond as strongly to insulin receptor signals resulting in less glucose being moved into the cell.

It modifies the activity of enzymes and their resulting reactions. It builds muscle tissue following sickness or injury by transporting amino acids to the tissue. It also helps regulate the uptake of amino acids, DNA replication, and protein synthesis. It manages lipid synthesis, breakdown of proteins and lipids due to fat cell changes, and allows for cell uptake of amino acids and potassium. Insulin manages excretion of sodium and the fluid volume of urine. And finally it plays a role in enhancing learning and memory.

Genetic and Historical Relevance

Prior to the manufacturing of insulin, physicians generally recommended dieting to control starch and sugar intake. Without proper treatment, patients with diabetes notably children would have lower life expectancies with high risk of coma, glucosuria, acidosis, and death.

Insulin was first discovered in 1922 after many failed attempts at isolating pancreatic extracts to lower blood sugar. This success came by isolating pancreatic islet extracts using dogs and an injection of the islet extracts were first tested on a 14 year old boy in January of 1922 who showed a good prognosis soon after. The scientists involved, Frederick Banting, John Macleod, and Charles Best were awarded the Nobel Prize in 1923.

Amid many changes over time to the maintenance and production of the protein, it became the first human protein to be manufactured through biotechnology in 1978. Recombinant DNA techniques were used to produce synthetic human insulin. This was more useful than older attempts to produce and use pig insulin since this synthetic insulin was less likely to result in allergic reactions than animal insulin.

Scientists inserted the human insulin gene into plasmids, inserted them into recombinant bacterium and allowed them to grow inside a fermentation tank. They then took the protein made and purified into a drug for use.

Insulin has come a long way since then, being placed in pumps, pens, and even islet cell transplantations to help diabetes patients manage the disease. A very exciting new development in 2015, was the iLet: a bionic pancreas that provides insulin and glucagon as required.

Diseases

Insulin is related to a number of diseases the most well known being diabetes. Type 1 diabetes, or juvenile diabetes, is a condition in which the pancreas doesn't produce insulin properly. Type 2 diabetes occurs when your body does not utilize insulin properly (insulin resistance).

Other related conditions include insulin autoimmune disorder which causes hypoglycemia because the body begins to make antibodies that attack insulin, acidosia, glycosuria, and a multitude of other symptoms.