Insulin

Insulin
[[File:|250px]] Chemical structure of human insulin
Abbreviation	INS
Molecular formula	C257H383N65O77S6
Type	Peptide
Administration	Subcutaneous injection, intravenous, intramuscular
Bioavailability	Negligible (oral)
Synonyms	Human insulin, regular insulin
Source	Beta cells of the pancreatic islets
Ray's verdict	"Insulin is important in the regulation of blood sugar, but its importance has been exaggerated because of the diabetes/insulin industry. Insulin itself has been found to account for only about 8% of the 'insulin-like activity' of the blood, with potassium being probably the largest factor." – Ray Peat

Introduction

Insulin is a peptide hormone produced by beta cells in the islets of Langerhans of the pancreas. It plays a crucial role in regulating blood glucose levels by facilitating the uptake of glucose into cells for energy production or storage. Deficiency or resistance to insulin leads to diabetes mellitus, a condition characterized by hyperglycemia. Insulin was first isolated in 1921 and has since become a cornerstone in the management of diabetes.

History/Etymology

The term "insulin" derives from the Latin word "insula," meaning island, referring to the islets of Langerhans where it is produced. The concept of a pancreatic substance regulating glucose metabolism was hypothesized as early as 1910 by Edward Albert Sharpey-Schafer. The discovery of insulin occurred in 1921 at the University of Toronto by Frederick Banting and Charles Best, assisted by J.J.R. Macleod and James Collip. They successfully extracted insulin from dog pancreases and demonstrated its ability to lower blood sugar in diabetic dogs. The first human administration was in January 1922 to Leonard Thompson, a 14-year-old boy with type 1 diabetes. In 1923, Banting and Macleod received the Nobel Prize in Physiology or Medicine for this work. Prior to insulin's discovery, diabetes was often fatal, managed only through starvation diets.

Structure/Chemical properties

Human insulin is a small protein consisting of 51 amino acids divided into two polypeptide chains: the A chain (21 amino acids) and the B chain (30 amino acids). These chains are linked by two interchain disulfide bonds, with an additional intrachain disulfide bond in the A chain. Its molecular mass is approximately 5808 Da, and the chemical formula is C257H383N65O77S6. Insulin exists as a monomer in solution but forms dimers and hexamers in the presence of zinc ions, which stabilizes storage in the pancreas. It is soluble in water at neutral pH but precipitates at its isoelectric point around pH 5.4. Modifications to the structure have led to analog insulins with altered pharmacokinetics.

Function/Mechanism of Action

Insulin's primary function is to lower blood glucose by promoting its uptake into muscle, adipose, and liver cells via the GLUT4 transporter. It stimulates glycogenesis, lipogenesis, and protein synthesis while inhibiting gluconeogenesis, glycogenolysis, and lipolysis. At the cellular level, insulin binds to its receptor, a tyrosine kinase, triggering a cascade that phosphorylates insulin receptor substrates (IRS), activating PI3K-Akt and MAPK pathways. This leads to translocation of GLUT4 vesicles to the cell membrane and metabolic shifts favoring anabolism. Ray Peat notes that insulin inhibits lipolysis, reducing free fatty acids and supporting glucose oxidation, but its role is only about 8% of blood's insulin-like activity, with potassium being a major factor.

Medical uses/Effects

Insulin is primarily used to treat type 1 diabetes, where the body produces little to no insulin, and in advanced type 2 diabetes when oral agents fail. It is also used for gestational diabetes, diabetic ketoacidosis, and hyperosmolar hyperglycemic state. Therapeutic effects include rapid normalization of blood glucose, prevention of long-term complications like retinopathy, nephropathy, and neuropathy, and improved energy metabolism. In non-diabetics, it has been explored for wound healing and certain metabolic disorders. According to Ray Peat, insulin can exacerbate some diabetes complications like retinal damage, and diabetes often involves normal or high insulin levels rather than deficiency.

Dosing

Dosing is individualized based on body weight, blood glucose monitoring, diet, and activity. Typical starting doses for type 1 diabetes are 0.4-1.0 units/kg/day, split between basal (long-acting) and bolus (short-acting) insulins. Regimens include basal-bolus, premixed, or insulin pump therapy. Adjustments are made via sliding scales or carbohydrate counting. Long-acting analogs like glargine provide steady coverage, while rapid-acting like lispro cover meals.

Side/Adverse effects

Common side effects include hypoglycemia (low blood sugar), which can cause sweating, tremors, confusion, and seizures if severe. Weight gain occurs due to anabolic effects. Injection site reactions like lipodystrophy may develop. Rare but serious effects include allergic reactions, insulin resistance from antibodies, and hypokalemia. Overdose can lead to coma. Ray Peat highlights that excess insulin can cause vascular leakiness and that insulin treatment itself poses health risks, potentially worsening conditions like retinal damage.