The name insulin comes from the Latin insula, for islands. It refers to thepancreatic islets of Langerhans that contain the beta cells.
The Islets of Langerhans
The pancreas contains one to three million islets of Langerhans, but the isletsaccount for only 2 percent of the total mass of the pancreas. The rest of thepancreas secretes a juice containing digestive enzymes that break down food.Within the islets of Langerhans, beta cells constitute 60 to 80 percent of allthe cells.
A Once Elusive Hormone
Before Banting and Best, researchers couldn't find insulin because the digestivejuices put out by the pancreas digested it all. Banting and Best's trick was totie a string around the pancreatic duct of a live dog. When the dog was examinedseveral weeks later, the pancreatic digestive cells had died and had beenabsorbed by the immune system, leaving the thousands of islets. They thenisolated an extract from these islets, producing what they called isletin(insulin).
Detecting Insulin's Sequence
Insulin was the first protein ever to have its sequence determined. The exactsequence of amino acids comprising the insulin molecule was found by Britishmolecular biologist Frederick Sanger, who was awarded the 1958 Nobel Prize inChemistry. In 1969, Dorothy Crowfoot Hodgkin determined the spatial conformationof insulin, or how it's twisted in space.
What md/dl Stands for
The abbreviation mg/dl stands for milligrams of glucose in 100 milliliters (onedeciliter) of blood. A milligram equals .0000353 of an ounce, and 100milliliters equals something less than half a cup. In a healthy adult male of165 pounds with a blood volume of about five quarts, a blood glucose level of100 mg/dl corresponds to about 1/5 ounce of glucose in the blood andapproximately 1½ ounces in the total body water. All the glucose in your bloodamounts to about the contents of a restaurant sugar packet.
All Creatures, Great and Small, Need It
Insulin is required for all animal life, and it works just about the same innematode worms, fish and mammals like us. The initial sources of insulin forclinical use in humans were cow, horse, pig or fish pancreases. They all workbecause they're nearly identical to human insulin. Cow insulin differs fromhuman by only three amino acids, and pig insulin by only one. Before humanrecombinant analogues were available, Novo Nordisk was able to convert piginsulin into human insulin by removing the single different amino acid andchemically adding the correct one.
Hard to Swallow
Unlike many medicines, insulin cannot be taken orally. Like nearly all otherproteins, it is digested into useless fragments in the gastrointestinal tract.
Where Old Insulin Goes
What happens to your old insulin? Once an insulin molecule has docked onto thereceptor and done its work, it may be released back into the extracellularenvironment or it may be degraded, usually by liver cells.
Zinc's Important Role
Unmodified human insulin tends to join up with zinc in the blood, forminghexamers, which means six monomers; that is, six single molecules of insulinstuck together. Insulin in the form of a hexamer will not bind to its receptors,so the hexamer has to slowly turn back into single monomers before it can work.That's why zinc combinations of insulin are used to make slow release basalinsulin. Ultralente insulin (no longer available) was a good example of this useof zinc.
Lilly had the first insulin analog with "lispro," a rapid acting insulin analogwith the trade name of Humalog®. It's called lispro because they reversedthe positions of lysine and proline in the insulin. This modification did notalter receptor binding, but blocked the formation of insulin dimers (two joinedinsulin molecules) and hexamers. This allowed larger amounts of active monomericinsulin to be available in the body.
Novo Nordisk created "aspart" and marketed it as NovoLog, a rapid acting insulinanalogue. It's called aspart because they switched the normal proline amino acidfor an aspartic acid residue. This analogue also prevents the formation ofhexamers, to create a faster acting insulin.
Aventis developed glargine (Lantus) as a longer lasting insulin analogue. It wascreated by adding two arginines and switching another molecule for glycine.