Insulin

= Insulin =

General information
toc


 * ~ Product Name || Insulin ||
 * ~  Discoverer ||  Paul Langerhans  ||


 * ~ Patent holders || No laws exist to deal with the issue of biological patents and because of this most companies found the existing insulin patents too hard to challenge ||


 * ~ Area of Application || Health Care ||

Insulin is a hormone, secreted by a group of cells within the pancreas called I slets cells that in response to a detected increase in blood sugar, take up glucose from the blood, storing it as glycogen in the liver and muscle. Properties of the Insulin Protein (//Homo sapiens//):
 * Number of amino acids:** 110
 * Molecular weight:** 11980.9
 * Theoretical pI:** 5.22
 * Total number of negatively charged residues (Asp + Glu):** 10
 * Total number of positively charged residues (Arg + Lys):** 7
 * Atomic composition:** Carbon C 535 Hydrogen H 841 Nitrogen N 143 Oxygen O 153 Sulfur S 8
 * Formula:** C535H841N143O153S8
 * Total number of atoms:** 1680
 * Extinction coefficients:** Extinction coefficients are in units of M-1 cm-1, at 280 nm measured in water. Ext. coefficient 17335 Abs 0.1% (=1 g/l) 1.447, assuming ALL Cys residues appear as half cystines Ext. coefficient 16960 Abs 0.1% (=1 g/l) 1.416, assuming NO Cys residues appear as half cystines
 * Estimated half-life:** The N-terminal of the sequence considered is M (Met). The estimated half-life is: 30 hours (mammalian reticulocytes, in vitro). >20 hours (yeast, in vivo). >10 hours (Escherichia coli, in vivo).
 * Instability index:** The instability index (II) is computed to be 40.33 This classifies the protein as unstable.
 * Aliphatic index:** 102.91
 * Grand average of hydropathicity (GRAVY):** 0.193

History
In 1869, Paul Langerhans identified some previously unnoticed tissue clumps scattered throughout the bulk of the pancreas when he was studying its structure under a microscope. Later in 1889, Oscar Minkowski and Joseph von Mering tied a string around the pancreatic duct of several dogs. When they examined the pancreases of these dogs some weeks later, all of the pancreas digestive cells died and were absorbed by the immune system, the only thing left was thousands of pancreatic islets. [1] They then isolated the protein from these islets, and they discovered insulin. Over the next two decades, several attempts were made to isolate whatever the islets produced as a potential treatment. The first successful insulin preparations come from cows (and later pigs): the bovine and porcine insulin were purified, bottled, and sold. Bovine and porcine insulin worked very well (and still do!) for the vast majority of patients, but some could develop an allergy or other types of reactions to the foreign protein. In the 1980's technology had advanced to the point where we could make human insulin. The advantage would be that human insulin would have a much lower chance of inducing a reaction because it is not a foreign protein. The technology which made this approach possible was the development of recombinant DNA techniques. From this, pharmaceutical companies can isolate pure human insulin. [2] Nicolae Paulescu was the first one to isolate insulin and his techniques was patented in Romania, though no clinical use resulted. The amino-acid structure of insulin was characterized in the 1950s and the first synthetic insulin was produced simultaneously. The first genetically-engineered, synthetic "human" insulin was developed in a laboratory in 1977 by Herbert Boyer  through a   partnership with Genentech[3].

Structure
This endocrine hormone has a compact three-dimensional structure consisting of three short helices and three invariant disulfide bridges. Its quaternary conformation can adopt a therapeutically-significant "R" or "T" state. A single molecule of insulin acts as a bivalent ligand to the insulin receptor, by way of two binding surfaces.[4] 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. [5] In most species, the A chain consists of 21 amino acids and the B chain of 30 amino acids meaning that it is composed of 51 amino acids in the two peptide chains (A and B). Notably, the positions of these three disulfide bonds are invariant in mammalian forms of insulin. Species Sequence Alignment of Insulin code Human     MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREAED 60 Chimpanzee MALWMRLLPLLVLLALWGPDPASAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREAED 60 Mouse     MALLVHFLPLLALLALWEPKPTQAFVKQHLCGPHLVEALYLVCGERGFFYTPKSRREVED 60 Rabbit    MASLAALLPLLALLVLCRLDPAQAFVNQHLCGSHLVEALYLVCGERGFFYTPKSRREVEE 60 Frog      MALWMQCLPLVLVLFFSTPN-TEALVNQHLCGSHLVEALYLVCGDRGFFYYPKVKRDMEQ 59 Zebrafish MAVWLQAGALLVLLVVSSVS-TNPGTPQHLCGSHLVDALYLVCGPTGFFYNPK--RDVEP 57 **     .*: :* .   . : . . *****.***:*******  **** **  *: *

Human     LQVG---QVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN 110 Chimpanzee LQVG---QVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN 110 Mouse     PQVE---QLELGGSPGD--LQTLALEVARQKRGIVDQCCTSICSLYQLENYCN 108 Rabbit    LQVG---QAELGGGPGAGGLQPSALELALQKRGIVEQCCTSICSLYQLENYCN 110 Frog      ALVSGPQDNELDG--MQLQPQEYQKMKRGIVEQCCHSTCSLFQLESYCN 106 Zebrafish -LLG-FLPPKSAQETEVADFAFKDHAELIRKRGIVEQCCHKPCSIFELQNYCN 108 :     :         :          *****:*** . **:::*:.*** code

Market and Applications
Insulin is used medically to treat some forms of diabetes mellitus. Patients with Type I diabetes mellitus depend on external insulin (most commonly injected subcutaneously) for their survival because the hormone is no longer produced internally. Patients with Type II diabetes mellitus are insulin resistant, have relatively low insulin production, or both; certain patients with Type 2 diabetes, on rare occasions, may eventually require insulin if other medications fail to control blood glucose levels adequately. [5] Without insulin, you can eat lots of food and actually be in a state of starvation since many of our cells cannot access the calories contained in the glucose very well without the action of insulin. This is why people with type I diabetes who do not make insulin can become very ill without insulin shots. More commonly, people will develop insulin resistance (type II diabetes) rather than a true deficiency of insulin. In this case, the levels of insulin in the blood are similar than in people without diabetes. However, many cells of people with type II diabetes respond sluggishly to the insulin they make and therefore their cells cannot absorb the sugar molecules well. This leads to blood sugar levels which run higher than normal. Occasionally people with type II diabetes will need insulin shots, but most of the time other methods of treatment will work.