Insulin
Insulin is a hormone found in the human body. It is secreted by the islets of Langerhans in the pancreas. Insulin is composed of two chains of amino acids, an A chain of 21 amino acids containing an intrachain disulfide linkage and a B chain of 30 amino acids. The two chains are linked together by two other disulfide linkages, the destruction of which destroys the activity of the molecule. Insulin is classified as a peptide hormone.
Secretion and Production
Insulin is synthesized in humans and other mammals within the beta cells of the islets of Langerhans in the pancreas. From one to three million islets of Langerhans form the endocrine part of the pancreas. The endocrine part accounts for only 2% of the total mass of the pancreas. Within the islets of Langerhans, beta cells constitute 60–80% of all the cells.
In beta cells, insulin is synthesized from the proinsulin precursor molecule by the action of proteolytic enzymes known as prohormone convertases, as well as the exoprotease carboxypeptidase E. These modifications liberate the center portion of the molecule, or C-peptide, from the C- and N- terminal ends of the proinsulin. The two remaining polypeptides, the B- and A- chains, are held together by disulfide bonds and together constitute 51 amino acids. Confusingly, the primary sequence of insulin goes in the order “B-C-A”, since B and A chains were identified on the basis of mass, and the C peptide was discovered after the others.
Secretion of insulin has many effects on the human body. Most prominently, it regulates carbohydrate metabolism. On a metabolic level, insulin secretion controls the glucose intake of both muscle and adipose tissue. It increases DNA replication and protein synthesis by controlling amino acid uptake. Finally, it modifies the activity of numerous enzymes.
On the cellular level, insulin increases glycogen synthesis, decreasing the glucose level in the blood. It increases both fatty acid synthesis and the etherification of fatty acids. It decreases proteinolysis, lipolysis, and gluconeogenesis. Finally, it increases amino acid and potassium uptake.
Pharmacological Uses
The hormone insulin was first discovered by a medical student in Berlin in 1869. However, the first treatment by use of insulin wasn’t until 1922. In this case, a 14-year old boy, Leonard Thompson, was given bovine insulin as a treatment for his diabetes. Bovine insulin was used for several decades to treat humans, but treating diabetes with bovine insulin had a high risk of allergic reaction due to its impurity.
In 1982, Eli Lilly, a pharmaceutical company, marketed the first form of recombinant human insulin. It was called Humilin, and the process used to manufacture it was developed by Genentech. This is the current form of diabetes treatment.
Insulin must be injected subcutaneously for it to be effective. Its only common use is for treatment of type 1 diabetes. Diabetes is a condition in which the pancreas stops producing insulin. This leads to dangerously high blood-glucose levels. Diabetics must treat this condition with insulin for the duration of their lives.
Although injections of insulin do work to sustain the lives of diabetics, there still remain several problems to its use. Most cases of hypoglycemic shock are a result of diabetics miscalculating their blood-sugar level. If they inject too much insulin, exercise too much, or eat too little, they’re in risk of having their blood-sugar drop to dangerously low levels. Conversely, if they inject too little insulin, exercise too little, or eat too much, they’re in risk of having their blood-sugar level rise too high. Both have damaging effects on the body; however, low blood-sugar levels have immediate detrimental effects where high blood-sugar levels are only detrimental over long periods of time.
The only other common use of insulin is as a performance-enhancing drug generally in combination with synthetic somatropin use. Because insulin has the ability to store nutrients into cells, it’s popular among athletes who want to increase their muscle mass. Because of its potential side effects, mainly hypoglycemia, this use of insulin is not medically approved, and it is illegal in most sports.