[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Insulin signalling [Biochemistry](https://durgical.com/en/biochemistry/) · Topic # 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. ## In detail - 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. ## Clinical notes - 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. ## Pathways - [Glycogen metabolism](https://durgical.com/en/biochemistry/pathways/glycogen-metabolism/) - [Glycolysis](https://durgical.com/en/biochemistry/pathways/glycolysis/) - [Fatty acid synthesis (lipogenesis)](https://durgical.com/en/biochemistry/pathways/fatty-acid-synthesis/) ## Related conditions - [Type 1 diabetes mellitus](https://durgical.com/en/conditions/type-1-diabetes-mellitus/) - [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/) - [Diabetic ketoacidosis](https://durgical.com/en/conditions/diabetic-ketoacidosis/) - [Metabolic syndrome](https://durgical.com/en/conditions/metabolic-syndrome/) ## Related - [Insulin receptor](https://durgical.com/en/biochemistry/enzymes/insulin-receptor/) - [Receptor tyrosine kinases](https://durgical.com/en/biochemistry/topics/receptor-tyrosine-kinases/) - [mTOR (mechanistic target of rapamycin)](https://durgical.com/en/biochemistry/enzymes/mtor/) - [Glucagon signalling](https://durgical.com/en/biochemistry/topics/glucagon-signalling/) - [Fed, fasting and starvation states](https://durgical.com/en/biochemistry/topics/fed-fasting-and-starvation-states/) - [Glycogen synthase](https://durgical.com/en/biochemistry/enzymes/glycogen-synthase/) - [Acetyl-CoA carboxylase (ACC)](https://durgical.com/en/biochemistry/enzymes/acetyl-coa-carboxylase/) - [Hormone-sensitive lipase (HSL)](https://durgical.com/en/biochemistry/enzymes/hormone-sensitive-lipase/) - [Lipoprotein lipase (LPL)](https://durgical.com/en/biochemistry/enzymes/lipoprotein-lipase/) - [Glucose](https://durgical.com/en/biochemistry/molecules/glucose/) - [Cyclic AMP (cAMP)](https://durgical.com/en/biochemistry/molecules/cyclic-amp/) ## Test yourself 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. [Add to my cards (5)](https://durgical.app/estudiar/?add=/en/biochemistry/topics/insulin-signalling/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [INS: Insulin (human)](https://www.uniprot.org/uniprotkb/P01308/entry) (UniProt, 2026); [INSR: Insulin receptor (human)](https://www.uniprot.org/uniprotkb/P06213/entry) (UniProt, 2026); [INSR gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/insr/) (MedlinePlus, US National Library of Medicine, 2026); [Insulin C-peptide test: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/003701.htm) (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). [← All of biochemistry](https://durgical.com/en/biochemistry/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/biochemistry/topics/insulin-signalling/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/topics/insulin-signalling/