What is insulin?

Insulin is a vital, blood sugar–lowering, growth-promoting hormone that is produced in the beta cells of the pancreas.

The “storage hormone” insulin

  • promotes the uptake of glucose into muscle and fat cells
  • promotes the formation of energy stores (glycogen and fat) from glucose in liver, fat, and muscle cells
  • inhibits the breakdown of these energy stores
  • reduces glucose production in the liver (gluconeogenesis)
  • suppresses glucagon release from the alpha cells

All metabolic effects of insulin lower blood sugar. In this role, insulin is indispensable. Opposing insulin are hormones such as glucagon, adrenaline, and somatotropin. Together, they function in a regulatory system that keeps fasting blood sugar levels stable in healthy individuals, between 55 and 100 mg/dl (3.0–5.5 mmol/l).

Insulin is released into the bloodstream by the beta cells of the pancreas in the form of proinsulin. The C-peptide is cleaved off, leaving insulin, which consists of an A-chain and a B-chain of amino acids connected by two disulfide bridges. Pig insulin differs from human insulin at position 30 of the B-chain, where the amino acid threonine is replaced by alanine. In bovine insulin, two additional amino acids of the A-chain differ from human insulin. The similarity suggests that bovine and porcine insulin can also be used in humans.

Proinsulin, insulin, and C-peptide

How does insulin work?
On the surface of the cells where insulin acts (e.g., muscle cells, fat cells, liver cells), there are insulin receptors. They bind to insulin and are thereby activated. This triggers a chemical chain reaction that extends all the way to the nuclear membrane. The nuclear membrane is a thin layer that surrounds the cell nucleus. Inside the nucleus are the genes—the human genetic material. Just like on the cell surface, there are also receptors on the nuclear membrane, including the receptor PPAR gamma. When this receptor is activated as part of the chain reaction, certain genes in the nucleus begin to produce more glucose transporters (e.g., GLUT4). Once these transporters reach the cell surface, blood sugar can be taken up into the cell.

An untreated insulin deficiency leads

  • in the short term, to hyperglycemia and metabolic derangement
  • in the long term, to damage of small and large blood vessels and nerves
  • ultimately, to blindness, impotence, amputations, heart attack, and stroke

 

Insulin deficiency in type 1 and type 2 diabetes

  • In type 1 diabetes, there is an absolute insulin deficiency. The beta cells of the pancreas are destroyed and no longer secrete insulin. This deficiency must be compensated for (substituted) from the very beginning. Without insulin, people with type 1 diabetes die at a young age.
  • In type 2 diabetes, there is a relative insulin deficiency: the body can initially compensate for increasing insulin resistance or decreasing insulin production—through more physical activity and weight loss. If this is not successful, medication must be taken to lower blood sugar and/or insulin resistance (see oral antidiabetic drugs). The natural (physiological) blood sugar–lowering treatment is the administration of insulin.

 

When must insulin be administered?

  • In type 1 diabetes: always.
  • In type 2 diabetes: The stepwise treatment plan begins with education, dietary improvement, weight reduction, and physical activity as the basis of therapy. Your doctor will agree with you on a specific treatment goal. The benchmark is an HbA1c level of 6.5% (HbA1c = amount of glycated hemoglobin as a measure of blood sugar control over the past weeks). If the target is not reached after three months with these measures, oral antidiabetics are usually added, sometimes also insulin.
    Insulin treatment becomes necessary in type 2 diabetes at the latest when the therapeutic goal (usually HbA1c 6.5%, higher in older patients) cannot be reached with dietary changes, more physical activity, and oral antidiabetics (see insulin therapy). Insulin therapy is also indicated in type 2 diabetes in cases of severe inflammation or infections (e.g., infarction, infected diabetic foot), before surgery, and during pregnancy.

 

The goals of insulin therapy are

  • optimal metabolic control
  • the most flexible lifestyle possible and improved quality of life

History of Insulin

  • 1864 Josef Alexander Fles describes the relationship between the pancreas and diabetes.
  • 1869 Paul Langerhans discovers the islets (small endocrine glands in the exocrine pancreas, consisting of several cell types with their own vascular structure).
  • 1889 Oskar Minkowski and Josef von Mering remove the pancreas from dogs, thereby inducing diabetes mellitus. Soon after, the islets are suspected to be endocrine (hormone-producing) tissue.
  • 1906 German internist Prof. Georg Ludwig Zülzer administered, for the first time, a calf pancreas extract called Acomatol (manufactured by Schering) to a human.
  • 1909 Belgian pathologist Jean de Meyer (1878–1934) proposed the name insulin (“coming from the islets”), derived from the Latin insula for the yet unknown substance.
  • 1910 English physiologist Edward Albert Sharpey-Schafer called the substance missing in diabetics insulin.
  • 1916 Nicolae Paulescu succeeded for the first time in extracting insulin from pancreatic tissue. He called the preparation pancrein and patented the production process in Romania.
  • 1921 Frederick Banting and Charles Best extracted insulin, which they named isletin.
  • 1922 Banting and Best treated the 13-year-old Leonard Thompson with bovine insulin for the first time. Thompson survived 14 years before dying of pneumonia. The five-year-old Theodore Ryder, treated in the same year, survived 70 years.
  • 1923 Frederick Banting and John James Rickard Macleod received the Nobel Prize in Physiology or Medicine for the discovery of insulin.
  • 1928 Oskar Wintersteiner proved that insulin is a protein.
  • 1934 A. Scott developed the first zinc insulin.
  • 1936 Hans Christian Hagedorn introduced the first long-acting NPH insulin (Neutral Protamine Hagedorn).
  • 1958 Frederick Sanger received the Nobel Prize for his work on protein structure, especially insulin.
  • 1963 Helmut Zahn and his team achieved the world’s first chemical synthesis of insulin.
  • 1971 Blundell and his team discovered the three-dimensional protein structure of insulin.
  • 1982 Genentech succeeded in producing human insulin in large quantities using genetically modified bacteria.
  • 1985 Novo Nordisk introduced the first insulin pen.
  • 1996 Lispro/Humalog became the first rapid-acting insulin analogue.
  • 1998 Insulin aspart, another rapid-acting insulin analogue, was introduced.
  • 2000 Insulin glargine, the first long-acting insulin analogue, was introduced.
  • 2004 Insulin detemir (long-acting analogue) and insulin glulisine (rapid-acting analogue) were introduced.
  • 2013 Insulin degludec, a long-acting insulin analogue, was introduced.
  • 2017 Faster-acting insulin aspart, a rapid-acting analogue, was introduced.
  • 2024 Insulin icodec, a long-acting insulin with once-weekly administration, was introduced.