Insulin is a hormone produced by beta cells in the pancreas. It regulates blood glucose concentrations and coordinates the use and storage of nutrients. Its actions are central to metabolism and glucose homeostasis. The term also refers to pharmaceutical preparations that replace or supplement the body's insulin, particularly in the treatment of diabetes mellitus. Insufficient insulin production, reduced responsiveness to insulin, or both can cause persistently elevated blood glucose. (ncbi.nlm.nih.gov)
Structure and biosynthesis
Mature human insulin is a small protein containing 51 amino acids. Its A chain contains 21 residues and its B chain 30; two disulfide bonds connect the chains, while a third lies within the A chain. These bonds help maintain the molecular structure required for biological activity. Insulin is synthesized in beta cells within the pancreatic islets of Langerhans. (ncbi.nlm.nih.gov)
The human INS gene encodes preproinsulin, a precursor containing a signal sequence that directs the newly synthesized protein into the endoplasmic reticulum. Removal of this sequence produces proinsulin, which folds and forms disulfide bonds. During maturation in secretory granules, enzymes remove a connecting segment, C-peptide, leaving mature insulin. Insulin and C-peptide are released together in approximately equal molar amounts. Because injected insulin does not contain C-peptide, its measurement can help assess endogenous insulin secretion. (ncbi.nlm.nih.gov)
Regulation of secretion
Glucose is a principal stimulus for insulin release. Its metabolism in beta cells increases the ratio of ATP to ADP, closing ATP-sensitive potassium channels. The resulting electrical depolarization opens voltage-dependent calcium channels. Calcium entry triggers the fusion of insulin-containing granules with the cell membrane and release of their contents. This mechanism couples nutrient availability to hormone secretion. (pmc.ncbi.nlm.nih.gov)
Secretion is also influenced by amino acids, autonomic nervous activity, and intestinal hormones released after food intake. Insulin is normally secreted in pulses, with increased release following meals. In experimental measurements, a sudden rise in glucose commonly produces an early release of stored insulin followed by a more sustained phase. Disruption of these responses is part of beta-cell dysfunction in diabetes. (pmc.ncbi.nlm.nih.gov)
Receptor signaling and metabolic actions
Insulin acts by binding to the insulin receptor, a cell-surface receptor with tyrosine kinase activity. Binding activates intracellular signaling networks, including pathways involving insulin receptor substrates, phosphoinositide 3-kinase, and Akt. These signals change transporter activity, enzyme function, and gene expression rather than acting simply as a universal “key” that opens every cell to glucose. (pubmed.ncbi.nlm.nih.gov)
In skeletal muscle and adipose tissue, insulin promotes movement of the glucose transporter GLUT4 from intracellular vesicles to the cell surface, increasing glucose uptake. Muscle stores some of this glucose as glycogen. In adipose tissue, insulin favors nutrient storage and inhibits the breakdown of stored fat. Its actions also support protein synthesis and influence cellular growth. (ncbi.nlm.nih.gov)
In the liver, insulin promotes glycogen synthesis and suppresses glucose production, including gluconeogenesis, the formation of glucose from non-carbohydrate precursors. It also promotes lipid synthesis. These hepatic effects complement increased glucose uptake elsewhere, helping limit the rise in blood glucose after meals. Insulin's influence therefore extends beyond glucose transport to the coordinated handling of carbohydrates, fats, and proteins. (pubmed.ncbi.nlm.nih.gov)
Insulin deficiency and resistance
In type 1 diabetes, immune-mediated destruction of beta cells usually causes severe insulin deficiency. Exogenous insulin is consequently required to replace the missing hormone. This differs from type 2 diabetes, in which reduced responsiveness to insulin and inadequate compensatory secretion occur together. (ncbi.nlm.nih.gov)
Insulin resistance means that a given insulin concentration produces a diminished biological response. It can affect muscle glucose uptake, suppression of glucose production by the liver, and inhibition of fat breakdown. Beta cells may initially compensate by secreting more insulin. Blood glucose rises when compensation is insufficient. Thus, elevated circulating insulin does not necessarily indicate effective insulin action, and type 2 diabetes is not simply an absence of insulin. (ncbi.nlm.nih.gov)
Pharmaceutical preparations and delivery
Therapeutic preparations include human insulin and insulin analogues, whose molecular modifications alter absorption or duration of action. Products are grouped by their onset, peak effect, and duration into rapid-, short-, intermediate-, and long-acting categories. Basal insulin provides background activity, while mealtime insulin addresses glucose increases associated with eating. These preparations differ in pharmacological behavior and are not interchangeable solely on the basis of their name. (niddk.nih.gov)
Delivery methods include subcutaneous injections using syringes or pens, insulin pumps, and inhaled insulin preparations. Automated delivery systems combine glucose-sensing equipment with a pump and control software. A major adverse effect of insulin therapy is hypoglycemia, or excessively low blood glucose; severe episodes can cause loss of consciousness, seizures, or coma. (niddk.nih.gov)
Discovery and manufacture
In 1921, Frederick Banting and Charles Best conducted experiments at the University of Toronto in John Macleod's laboratory. James Collip subsequently contributed to purification of pancreatic extracts. Clinical treatment began in 1922, including treatment of Leonard Thompson. Banting and Macleod received the 1923 Nobel Prize in Physiology or Medicine for the discovery of insulin. (nobelprize.org)
Early commercial insulin came from animal pancreases. Recombinant DNA technology later enabled production of human insulin using genetically modified microorganisms. On October 28, 1982, the United States Food and Drug Administration approved Humulin, the first biosynthetic human insulin product and the first approved medical product derived from this technology. Recombinant production subsequently supported the development of insulin analogues with modified time-action profiles. (fda.gov)