How Insulin Works

Physiology explainer

How insulin works

Follow glucose and insulin through one day. The diagram and the traces run on the same clock, so every moment shows what the cells are doing and the blood levels that result.

Person
about 5%

Glucose units
Fasting07:40
Blood glucose88 mg/dL
Insulin8 µU/mL
Animated diagram: pancreas beta cell, alpha cell and gut above a blood vessel, liver and a muscle or fat cell below it. Numbered marks 1 to 8 match the steps listed under the diagram. BLOOD β-CELLpancreas GLUT1/2 ATP ↑ K⁺ channel open Ca²⁺ channel shut insulin granules 2 3 4 α-CELL glucagon high 8 GUT food to glucose empty 1 LIVER releasing glucose glycogen 7 MUSCLE / FAT CELL insulinreceptor signal low GLUT4 transporters 1 of 5 at surface 5 6
glucose insulin glucagon Ca²⁺

Speed

The numbered marks

  1. 1Glucose enters the blood. Carbohydrate from a meal is digested to glucose and absorbed from the gut.
  2. 2The β-cell senses glucose. Glucose enters through GLUT1/2 transporters and is burned to make ATP. More glucose means more ATP.
  3. 3Channels switch. Rising ATP closes K⁺ (K-ATP) channels. The membrane depolarises and Ca²⁺ channels open.
  4. 4Insulin is released. Ca²⁺ makes stored granules fuse with the membrane. Insulin and C-peptide enter the blood: a fast first burst, then a sustained second phase.
  5. 5Insulin binds its receptor. On muscle and fat cells this switches on a signal chain inside the cell (IRS, PI3K, Akt).
  6. 6GLUT4 moves to the surface. The signal sends GLUT4 transporters from storage vesicles to the membrane, and glucose flows into the cell.
  7. 7The liver stores glucose. Insulin stops the liver releasing glucose and promotes storage as glycogen.
  8. 8Fasting: glucagon takes over. With little insulin, α-cells release glucagon. The liver breaks down glycogen and makes new glucose, which keeps the brain supplied.

What to watch

    How the numbers are produced, and their limits

    Simulation. Blood values come from a small glucose and insulin model solved minute by minute for a 70 kg adult who eats 50 g, 70 g and 70 g of carbohydrate at 08:00, 13:00 and 19:30. Glucose rises with gut absorption and liver output. It falls with insulin-driven uptake, insulin-independent uptake (mainly the brain) and loss through the kidneys above about 180 mg/dL (10 mmol/L). Insulin secretion follows glucose with a fast first phase, a sustained second phase and a boost from gut hormones, and insulin is cleared from plasma with a half-life of about 5 minutes. The structure follows the Bergman minimal model and the Dalla Man meal model in simplified form.

    HbA1c setting. HbA1c is converted to average glucose with the ADAG relation eAG (mg/dL) = 28.7 × HbA1c − 46.7. For type 2, insulin sensitivity is reduced (more as HbA1c rises), early-phase secretion is blunted, and β-cell output is then adjusted until the 24-hour mean glucose equals that average. For type 1, β-cell output is zero and the size of background and mealtime doses is adjusted in the same way. Injected insulin follows a rapid-acting profile that peaks about an hour after the dose.

    Diagnostic ranges (ADA). HbA1c below 5.7% is normal, 5.7 to 6.4% is prediabetes, 6.5% or above is diabetes. Fasting glucose of 126 mg/dL (7.0 mmol/L) or above also indicates diabetes.

    Limits.

    • The curves are typical patterns, not a prediction for any person. Two people with the same HbA1c can have very different days.
    • HbA1c reflects roughly the past two to three months. Here one representative day is scaled to match it.
    • Exercise, stress, illness, the dawn phenomenon, fat and protein in meals, and glucose-lowering medicines other than insulin are not modelled.
    • Glucagon and the particle counts in the diagram are qualitative. Glucose and insulin values are quantitative model outputs.
    • This is teaching material. It must not be used for diagnosis or to choose insulin doses.

    Sources. Nathan DM et al., Diabetes Care 2008;31:1473 (ADAG, eAG). American Diabetes Association, Standards of Care in Diabetes, Diagnosis and Classification. Bergman RN et al., Am J Physiol 1979;236:E667. Dalla Man C, Rizza RA, Cobelli C, IEEE Trans Biomed Eng 2007;54:1740. DeFronzo RA, Diabetes 2009;58:773. Rorsman P, Ashcroft FM, Physiol Rev 2018;98:117.