Insulin signalling !

Insulin is the fed-state hormone: it makes muscle and fat take up glucose and makes the liver store instead of release.

Updated 2026-11-01

Key facts

The beta cell cuts proinsulin into insulin and C-peptide in equal amounts; C-peptide tells the body's own insulin from injected insulin.
Secretion: glucose enters the beta cell, glucokinase phosphorylates it, ATP rises, the K-ATP channel closes, the membrane depolarises and Ca²⁺ entry releases the granules.
The receptor is a tyrosine kinase: it activates IRS → PI3K → Akt (metabolic effects) and Ras → MAPK (growth).
Akt moves GLUT4 to the membrane of muscle and fat; liver and brain do not depend on GLUT4.
Insulin also drives potassium into cells (Na⁺/K⁺ pump): that is why it can cause hypokalaemia.

Insulin binds the receptor's α subunit; the β subunits phosphorylate each other on tyrosines and recruit the insulin receptor substrates (IRS-1, IRS-2).
IRS activates PI3K, which makes PIP3 in the membrane; PDK1 and mTORC2 activate Akt (protein kinase B).
Akt inhibits GSK3 (glycogen synthase stays active), activates PDE3B (cAMP falls and PKA switches off) and moves FoxO1 out of the nucleus (less PEPCK and glucose 6-phosphatase).
In the liver insulin activates a phosphatase that dephosphorylates PFK-2: fructose 2,6-bisphosphate rises and glycolysis speeds up. It also activates acetyl-CoA carboxylase and SREBP-1c (lipogenesis).
In adipose tissue it slows hormone-sensitive lipase (by lowering cAMP) and raises lipoprotein lipase: fat is stored.
The signal is switched off by phosphatases (PTP1B, PTEN) and by serine phosphorylation of IRS-1 (JNK, IKKβ, S6K1, PKC), a central mechanism of insulin resistance.

Type 1 diabetes: insulin is missing (autoimmunity against the beta cell). Type 2 diabetes: insulin resistance plus progressive beta-cell failure.
Sulfonylureas close the K-ATP channel and release insulin; diazoxide opens it and holds insulin back (used in insulinoma).
High insulin with low C-peptide suggests exogenous insulin; both high suggest an insulinoma or sulfonylureas.
Acanthosis nigricans (dark, velvety skin on the neck and armpits) is a sign of hyperinsulinaemia.

Think of the answer, then tap the question to see it.

What closes the beta cell's K-ATP channel after a meal?

The rise in ATP from glucose metabolism; closure depolarises the cell and Ca²⁺ entry releases insulin.

Which insulin receptor pathway moves GLUT4 to the membrane?

The IRS → PI3K → Akt pathway; the Ras–MAPK pathway mainly handles growth.

How does insulin stop lipolysis?

It activates phosphodiesterase 3B, cAMP falls and PKA stops activating hormone-sensitive lipase.

Which test tells the body's own insulin from injected insulin?

C-peptide: it is secreted with endogenous insulin and is absent from pharmaceutical insulins.

Why can insulin lower blood potassium?

Because it stimulates the Na⁺/K⁺-ATPase and potassium moves into cells.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: INS: Insulin (human) (UniProt, 2026); INSR: Insulin receptor (human) (UniProt, 2026); INSR gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Insulin C-peptide test: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.