Insulin
Also known as: C-peptide, proinsulin
The 51-amino-acid anabolic hormone of β cells — the only hormone that lowers blood glucose — which promotes uptake and storage of glucose, fat and amino acids and suppresses their release.
Overview
Synthesis: preproinsulin (rough ER) → proinsulin → in secretory granules, prohormone convertases remove the connecting C-peptide, leaving insulin's A chain (21 aa) and B chain (30 aa) linked by two disulfide bonds. Insulin and C-peptide are secreted in equimolar amounts, but C-peptide is not extracted by the liver and lasts longer, so it is the best measure of endogenous secretion.
Secretion: glucose enters β cells and is phosphorylated by glucokinase; the rise in ATP/ADP closes ATP-sensitive K⁺ channels (Kir6.2/SUR1), depolarising the cell; voltage-gated Ca²⁺ channels open and Ca²⁺ triggers exocytosis. Release is biphasic: a rapid first phase from docked granules (lost early in type 2 diabetes) and a sustained second phase. Incretins (GLP-1, GIP), amino acids and vagal acetylcholine amplify secretion.
Action: insulin binds the insulin receptor, a receptor tyrosine kinase (α2β2 tetramer). Autophosphorylation recruits IRS proteins, activating the PI3K–Akt pathway (metabolic effects, including translocation of GLUT4 to the membrane of skeletal muscle and adipocytes) and the Ras–MAPK pathway (growth). In the liver it stimulates glycogen synthesis and lipogenesis and inhibits gluconeogenesis, glycogenolysis and ketogenesis; in muscle it increases glucose uptake, glycogen and protein synthesis; in adipose tissue it increases glucose uptake and triglyceride storage (lipoprotein lipase ↑) and inhibits hormone-sensitive lipase. It also drives K⁺ into cells via Na⁺/K⁺-ATPase.
- Location
Source: β cells of the pancreatic islets. Targets: liver, skeletal muscle and adipose tissue (main); most tissues express receptors.
Function
- Lowers blood glucose: GLUT4-mediated uptake in muscle and fat; inhibition of hepatic glucose output.
- Promotes storage of glycogen, triglyceride and protein (anabolic).
- Inhibits lipolysis, ketogenesis and proteolysis.
- Shifts potassium into cells.
- Stimulates growth (with IGF-1 and GH).
- Physiology
Class: peptide (51 aa; two chains). Receptor: insulin receptor — tyrosine kinase (IRS → PI3K/Akt, MAPK). Half-life ≈5 min; ≈50 % removed on first pass through the liver. Insulin-independent glucose uptake occurs in brain, red cells, liver, kidney, intestine, β cells and lens.
- Regulation
Stimulated by glucose (main), amino acids (arginine, leucine), GLP-1 and GIP (incretins), glucagon, vagal stimulation (M3) and sulfonylureas. Inhibited by somatostatin, α2-adrenergic activity (epinephrine, norepinephrine), hypoglycaemia and diazoxide (opens K_ATP).
Clinical significance
Diabetes mellitus
Absolute deficiency (type 1, autoimmune β-cell destruction) or resistance plus relative deficiency (type 2). Insulin therapy uses rapid-acting analogues (lispro, aspart) with meals and long-acting analogues (glargine, degludec) as basal cover.
Hypoglycaemia and C-peptide
High insulin with high C-peptide suggests insulinoma or sulfonylurea use; high insulin with low C-peptide indicates exogenous insulin (factitious or accidental).
Hyperkalaemia treatment
IV insulin with glucose lowers plasma K⁺ within 15–30 min by shifting it into cells.
Test yourself
Which event directly triggers insulin exocytosis from a β cell after a rise in glucose?
- Opening of ATP-sensitive K⁺ channels
- Influx of Ca²⁺ through voltage-gated channels after depolarisation
- Binding of glucose to a membrane GPCR
- Activation of the insulin receptor tyrosine kinase
Answer: Influx of Ca²⁺ through voltage-gated channels after depolarisation
Glucose metabolism raises ATP, which closes K_ATP channels; the cell depolarises, voltage-gated Ca²⁺ channels open and the Ca²⁺ influx triggers granule exocytosis. Sulfonylureas close K_ATP channels directly.
During DKA treatment, why must potassium be monitored and replaced even if the initial serum K⁺ is high?
- Insulin causes renal K⁺ retention
- Total-body K⁺ is depleted; insulin and correction of acidosis drive K⁺ into cells, unmasking hypokalaemia
- Ketone bodies bind potassium
- Saline contains no sodium
Answer: Total-body K⁺ is depleted; insulin and correction of acidosis drive K⁺ into cells, unmasking hypokalaemia
Osmotic diuresis depletes total-body potassium, while insulin deficiency and acidosis shift K⁺ out of cells. Insulin activates Na⁺/K⁺-ATPase and moves K⁺ back in, so serum K⁺ can fall dangerously.
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.