Promotes storage of glucose, fat and protein, and drives potassium into cells
Mnemonic
“Insulin stores, glucagon mobilises”, and insulin acts on all three fuels:
- Carbohydrate - glucose uptake via GLUT4 in muscle and fat, glycogenesis, and inhibition of gluconeogenesis and glycogenolysis
- Fat - lipogenesis, and inhibition of lipolysis and ketogenesis
- Protein - amino acid uptake and protein synthesis, inhibiting proteolysis
Electrolytes: insulin drives potassium into cells, which is why it treats hyperkalaemia and why insulin deficiency contributes to the hyperkalaemia of ketoacidosis.
“GLUT4 is the insulin dependent one”: brain (GLUT1 and 3), liver and pancreatic beta cells (GLUT2) take up glucose without insulin, which is why the brain is spared in insulin deficiency and why hypoglycaemia is so dangerous.
Inhibition of lipolysis is the action lost first, which is why ketoacidosis is a disease of insulin deficiency (type 1) while type 2 diabetes, with residual insulin, tends to produce the hyperosmolar state instead.
Expansion
Carbohydrate
- Increases glucose uptake in muscle and adipose tissue by inserting GLUT4 transporters. Brain, liver, kidney and red cells do not need insulin for uptake
- Stimulates glycogenesis; inhibits glycogenolysis and gluconeogenesis
Fat
- Stimulates lipogenesis and lipoprotein lipase
- Inhibits hormone-sensitive lipase, so lipolysis and ketogenesis stop. This is why insulin deficiency causes ketoacidosis
Protein
- Increases amino acid uptake and protein synthesis; inhibits proteolysis
Electrolytes
- Drives potassium into cells by stimulating the sodium-potassium ATPase, exploited in treating hyperkalaemia
Insulin is released biphasically: a rapid first phase from stored granules, lost early in type 2 diabetes, then a sustained second phase.
Counter-regulatory hormones opposing it are glucagon, adrenaline, cortisol and growth hormone, which is why illness and steroids destabilise glycaemic control.