The hormone that manages the body's fuel supply, and what happens when the system breaks down
Every cell in the body runs on glucose, but glucose can't simply flood the bloodstream and let cells help themselves — levels have to be held within a narrow range, roughly 3.9–5.5 mmol/L (70–99 mg/dL) when fasting, tight enough that a doubling in either direction causes real harm. The hormone chiefly responsible for that control is insulin, produced by the pancreas. Diabetes mellitus is, at its core, a family of diseases in which this insulin system fails — either the hormone isn't made, isn't made enough, or the body's cells stop responding to it properly. This guide covers how insulin is made and how it acts on the body, then works through the major types of diabetes and how each one breaks the system differently.
The pancreas is mostly an exocrine gland, producing digestive enzymes that drain into the small intestine. But scattered through it, making up only about 1–2% of its mass, are roughly a million small clusters of hormone-producing cells called the islets of Langerhans, named after the German pathologist Paul Langerhans, who first described them in 1869 without knowing what they did. Each islet contains several distinct cell types, the two most important being directly opposed to one another in function.
| Cell type | Share of islet | Hormone produced | Effect on blood glucose |
|---|---|---|---|
| Beta (β) cells | ~54-60% | Insulin | Lowers it |
| Alpha (α) cells | ~33-36% | Glucagon | Raises it |
| Delta (δ) cells | ~10-12% | Somatostatin | Suppresses both insulin and glucagon release |
| PP cells | <5% | Pancreatic polypeptide | Regulates pancreatic secretion, appetite |
Beta cells and alpha cells work as a matched pair, constantly adjusting their output in opposite directions so that blood glucose is nudged back toward its narrow target range within minutes of drifting off it — a classic negative feedback loop, and one of the most tightly regulated systems in the entire body.
Beta cells don't simply hold a store of finished insulin waiting to be dumped into the blood — they continuously sense glucose and calibrate their output to match it, in a chain of events that takes only a minute or two from sensing to secretion.
GLUT1 and GLUT3 in human beta cells — GLUT2 plays this role in rodents), which let glucose flow in proportion to how much is outside, acting as the cell's built-in glucose sensor.KATP channels in the cell membrane, which normally let potassium leak out and keep the cell's internal voltage low.Insulin itself starts life as a single, longer chain called preproinsulin, which is trimmed down to proinsulin and finally folded and cut into its mature, active form: two short amino acid chains (the A-chain and B-chain) held together by sulfur-sulfur bonds. Insulin holds a particular place in the history of biochemistry — it was the first protein ever to have its complete amino acid sequence determined, by Frederick Sanger in 1955, a decade-long effort that won him the first of his two Nobel Prizes and effectively founded the field of protein sequencing.
Insulin's popular reputation as "the hormone that lowers blood sugar" understates the job — it's better described as the body's primary anabolic (building-up) signal, telling cells that fuel is plentiful and it's time to store energy rather than release it. It binds to the insulin receptor, a receptor tyrosine kinase sitting on the surface of target cells; binding triggers the receptor to phosphorylate itself and a set of relay proteins (IRS proteins), which in turn activate the PI3K–Akt signalling pathway inside the cell. In muscle and fat cells, this pathway's most visible effect is to move GLUT4 glucose transporters from internal storage vesicles out to the cell surface, opening the door for glucose to flow in — a door that stays largely shut without insulin's signal.
| Target tissue | Main effects of insulin |
|---|---|
| Skeletal muscle | Moves GLUT4 to the surface for glucose uptake; promotes glycogen storage and protein synthesis |
| Liver | Promotes glycogen synthesis from glucose; suppresses glucose production (gluconeogenesis) and glycogen breakdown |
| Adipose (fat) tissue | Promotes glucose uptake and conversion to fat (lipogenesis); strongly suppresses fat breakdown (lipolysis) |
| Brain | Mostly insulin-independent for glucose uptake, but insulin signalling here still affects appetite and metabolic regulation |
The liver is a special case: its glucose transporter, GLUT2, lets glucose in and out freely regardless of insulin. Instead, insulin controls the liver by switching its internal chemistry — turning on the enzyme glycogen synthase to pack glucose away as glycogen, and turning off the enzymes that generate new glucose from amino acids and fat breakdown products. An adult liver can store roughly 100g of glycogen, enough to help buffer blood glucose for several hours between meals.
Insulin rarely acts alone — it's paired at all times with glucagon, released by the alpha cells whenever blood glucose falls, doing almost exactly the opposite job. Glucagon signals the liver to break glycogen back down into glucose (glycogenolysis) and to manufacture fresh glucose from non-carbohydrate sources such as amino acids (gluconeogenesis), releasing it back into the bloodstream. Between meals and overnight, blood glucose is held steady almost entirely by this insulin-glucagon seesaw, without any conscious input at all; only when glycogen stores run low, such as during prolonged fasting or exercise, do other hormones (adrenaline, cortisol, growth hormone) get meaningfully involved.
Diabetes mellitus is diagnosed when blood glucose is chronically too high — a state called hyperglycaemia — because this insulin system is no longer keeping it in range. Diagnosis rests on one of a small set of standard blood tests, each of which reflects a different aspect of glucose control.
| Test | What it measures | Diabetes threshold |
|---|---|---|
| Fasting plasma glucose | Blood glucose after ≥8 hours without food | ≥7.0 mmol/L (126 mg/dL) |
| Oral glucose tolerance test (OGTT) | Blood glucose 2 hours after a standard 75g glucose drink | ≥11.1 mmol/L (200 mg/dL) |
| HbA1c (glycated haemoglobin) | Average blood glucose over the preceding ~2-3 months | ≥6.5% (48 mmol/mol) |
The HbA1c test works because glucose in the blood attaches slowly and irreversibly to haemoglobin inside red blood cells; since those cells live for about three months, the proportion of "sugar-coated" haemoglobin gives a rolling average of blood glucose exposure, without needing a fasting sample.
Type 1 diabetes is an autoimmune disease (see our guide to adaptive immunity for how this targeting mechanism normally works against real pathogens): the immune system mistakenly identifies the pancreas's own beta cells as a threat and destroys them, usually over a period of months to years, until so few remain that the body can no longer produce meaningful amounts of insulin. It accounts for roughly 5-10% of diagnosed diabetes cases and, although it can begin at any age, most often first appears in childhood or adolescence — historically it was called "juvenile diabetes" for this reason, though the label has fallen out of use since adult-onset cases are common too.
Because the beta cells themselves are gone, type 1 diabetes results in an absolute insulin deficiency — the body simply cannot make its own insulin, in any amount. There is no way to reverse the underlying beta-cell loss with current treatment, so lifelong insulin replacement, delivered by injection or pump, is required from diagnosis onward. Left untreated, the absence of insulin causes the body to break down fat for fuel instead, producing acidic byproducts called ketones that can build up into a dangerous, potentially fatal condition called diabetic ketoacidosis (DKA) — often the first sign that leads to a type 1 diagnosis in the first place.
Type 2 diabetes develops through a different, usually slower mechanism, and accounts for roughly 90-95% of all diabetes cases worldwide. It begins with insulin resistance — muscle, fat, and liver cells respond less strongly to insulin's signal than they should, so glucose uptake and liver glucose suppression are both blunted even when insulin is present. Initially, the beta cells compensate by producing more insulin than normal to force the message through, and blood glucose can stay near-normal for years. Over time, however, the beta cells' compensatory overwork tends to wear them down, and insulin production gradually declines — so established type 2 diabetes usually involves both resistance to insulin's effect and a genuine, if partial, shortfall in how much insulin the pancreas can still make.
Risk is shaped by a mix of genetics and lifestyle: excess body fat (particularly visceral fat around the abdominal organs), physical inactivity, and age are the best-established contributors, and family history plays a substantial role independent of weight. Because some functioning beta cells usually remain, especially early on, type 2 diabetes is often manageable initially through diet, exercise, and weight loss alone, followed by oral medications, and only progresses to require injected insulin once the pancreas's own output has fallen substantially.
| Type 1 Diabetes | Type 2 Diabetes | |
|---|---|---|
| Underlying cause | Autoimmune destruction of beta cells | Insulin resistance, plus progressive beta-cell decline |
| Insulin levels | Absent or near-absent | Normal, high, or gradually falling |
| Typical onset | Often childhood/adolescence, can be any age | Usually adulthood, increasingly seen in younger people too |
| Onset speed | Often rapid (weeks) | Usually gradual (years) |
| Body weight link | No consistent link | Strongly associated with excess weight, though not universal |
| Initial treatment | Insulin, immediately and always | Lifestyle change, then oral medication, then often insulin |
| Share of cases | ~5-10% | ~90-95% |
Type 1 and type 2 are the overwhelming majority of cases, but several other distinct forms exist, each breaking the insulin system in its own particular way.
Develops during pregnancy, driven by placental hormones that increase insulin resistance to help divert nutrients toward the growing fetus. It usually resolves after delivery, but it marks a substantially raised lifetime risk of later developing type 2 diabetes for the mother, and can affect the baby's birth weight and later metabolic health if untreated.
A group of rare, inherited forms caused by a mutation in a single gene affecting beta-cell function, passed on in a dominant pattern — meaning a child of an affected parent has a 50% chance of inheriting it. It typically appears before age 25 and is often initially misdiagnosed as type 1 or type 2, since it doesn't fit either pattern cleanly; genetic testing is needed to confirm it, and treatment can differ substantially depending on the specific gene involved.
Sometimes informally called "type 1.5," LADA is genuinely autoimmune in origin — the same underlying process as type 1 — but progresses far more slowly, so it's frequently misdiagnosed as type 2 at first, particularly since it appears in adults. It eventually leads to full insulin dependence as the more gradual beta-cell destruction runs its course.
Diabetes arising as a direct consequence of damage to the pancreas itself — from chronic pancreatitis, cystic fibrosis, pancreatic cancer, or surgical removal of part of the pancreas — or from other endocrine disorders and certain medications, such as long-term high-dose corticosteroids, that interfere with insulin action or production.
Whatever the underlying type, sustained high blood glucose is directly damaging to blood vessels and nerves throughout the body, which is why long-term complications look broadly similar across all forms of diabetes, differing mainly in how quickly they tend to develop.
| Category | Affected vessels | Examples |
|---|---|---|
| Microvascular | Small blood vessels | Retinopathy (eyes), nephropathy (kidneys), neuropathy (nerves) |
| Macrovascular | Large blood vessels | Heart attack, stroke, peripheral artery disease |
Because these complications develop gradually and often silently over years, ongoing monitoring — regular HbA1c testing, eye exams, kidney function tests, and foot checks — is a core part of long-term diabetes management, alongside the direct glucose-lowering treatment itself.
Before 1921, a diagnosis of type 1 diabetes was effectively a death sentence, typically within a year or two, with the only available "treatment" being extreme starvation diets that merely delayed the inevitable. That changed with a series of experiments at the University of Toronto by Frederick Banting and his student assistant Charles Best, working in the laboratory of J.J.R. Macleod, with biochemist James Collip developing a method to purify the extract enough for human use. In January 1922, a 13-year-old patient named Leonard Thompson received the first injection of insulin extracted from animal pancreases; this initial, impure extract had little therapeutic effect and caused an allergic reaction. Twelve days later, a second injection made from a purified extract developed by Collip produced a dramatic improvement in his blood glucose, making Thompson the first person successfully treated with insulin. He lived another 13 years.
Banting and Macleod received the Nobel Prize in Physiology or Medicine in 1923, a decision Banting considered so unjust to Best's contribution that he split his own prize money with him. For six decades afterward, insulin for treatment was extracted from the pancreases of cattle and pigs, effective but always in limited supply. That changed in 1978, when scientists at Genentech used recombinant DNA techniques to insert the human insulin gene into E. coli bacteria, engineering them to manufacture genuine human insulin directly. The resulting product, Humulin, was approved in 1982 as the first genetically engineered drug ever brought to market — and the same recombinant approach remains the basis of essentially all insulin produced today.
This document provides a general scientific overview of diabetes and insulin for educational purposes, and is not medical advice.