Physiology chapters
Insulin and glucagon
The islet cells and their hormones, how insulin is released and what it does to carbohydrate, fat, protein and potassium, which tissues need insulin to take up glucose, and how glucagon acts on the liver, with the basis of diabetes.
- Beta cells make insulin, alpha cells make glucagon, delta cells make somatostatin.
- Insulin is the hormone of the fed state: it lowers blood glucose, stores glycogen, fat and protein, and moves K+ into cells; muscle and fat need it to take up glucose (GLUT4).
- Glucagon is the hormone of fasting: on the liver it increases glycogenolysis, gluconeogenesis and ketogenesis and reduces lipogenesis.
On this page
Overview
The pancreas has an exocrine part (digestive enzymes) and an endocrine part: about one to two million islets of Langerhans.
| Islet cell | Share (approx.) | Hormone |
|---|---|---|
| Beta (β) | 60% | Insulin (and amylin) |
| Alpha (α) | 25% | Glucagon |
| Delta (δ) | 10% | Somatostatin (inhibits both insulin and glucagon) |
| PP cells | Few | Pancreatic polypeptide |
Insulin and glucagon have opposite effects and keep blood glucose in a narrow range.
Insulin secretion
Insulin is made as proinsulin, which is cut into insulin and C-peptide. Both are released in equal amounts.
How glucose triggers release
- Glucose enters the beta cell through GLUT2.
- Glucokinase phosphorylates it; it is metabolised, raising ATP.
- ATP closes ATP-sensitive K+ channels.
- The cell depolarises.
- Voltage-gated Ca2+ channels open; Ca2+ enters.
- Ca2+ triggers exocytosis of insulin.
Sulfonylurea drugs (glibenclamide) close the KATP channels, so they release insulin even without a rise in glucose.
Other factors
| Increase insulin | Decrease insulin |
|---|---|
| High glucose (main stimulus) | Low glucose |
| Amino acids (arginine) | Somatostatin |
| Gut hormones (GLP-1, GIP: incretins), so oral glucose releases more insulin than IV | Adrenaline and noradrenaline (α2) |
| Glucagon, vagal (parasympathetic) stimulation | Fasting |
C-peptide is used to tell the body's own insulin from injected insulin (which has no C-peptide).
Actions of insulin
Insulin is the hormone of plenty: it stores fuel.
Carbohydrate
- ↑ Glucose uptake into muscle and fat (moves GLUT4 to the membrane).
- Liver: activates glucokinase (traps glucose in liver cells) and glycogen synthase → glycogen storage; inhibits glycogenolysis and gluconeogenesis.
- Net effect: ↓ blood glucose.
Fat
- ↑ Fat synthesis (lipogenesis) in liver and fat cells; extra glucose is turned into fatty acids.
- ↑ Lipoprotein lipase in fat tissue, which takes fat from the blood.
- Inhibits hormone-sensitive lipase, so lipolysis falls.
- Lack of insulin → fat breakdown → free fatty acids → ketone bodies in the liver.
Protein
- ↑ Amino acid uptake and protein synthesis.
- ↓ Protein breakdown.
- Works with growth hormone for growth.
Potassium
Insulin stimulates the Na+/K+-ATPase, moving K+ into cells.
Insulin with glucose is used to treat hyperkalaemia quickly. Insulin treatment in diabetic ketoacidosis can cause hypokalaemia, so K+ is monitored and replaced.
Insulin-dependent and independent glucose uptake
| Insulin-dependent (GLUT4) | Insulin-independent |
|---|---|
| Skeletal muscle at rest | Brain (GLUT1/3) |
| Adipose tissue | Red blood cells (GLUT1) |
| Heart muscle (partly) | Liver (GLUT2; insulin acts on glucokinase, not transport) |
| Kidney, beta cells, gut, lens, nerves |
Exercising muscle takes up glucose without much insulin, because contraction itself moves GLUT4 to the membrane. That is why exercise lowers glucose in diabetes.
The liver does not need insulin for glucose entry (GLUT2), but insulin increases glucokinase, which keeps glucose inside the cell.
The brain uses glucose without insulin, so hypoglycaemia affects the brain first and most severely.
Glucagon
Control
| Increase glucagon | Decrease glucagon |
|---|---|
| Low blood glucose (main stimulus) | High glucose |
| Amino acids (after a protein meal) | Insulin, somatostatin |
| Exercise, stress, sympathetic stimulation | Free fatty acids, ketones |
Actions
Glucagon acts mainly on the liver, through cAMP:
| Effect | Result |
|---|---|
| ↑ Glycogenolysis | Rapid rise in blood glucose |
| ↑ Gluconeogenesis | Sustained glucose supply (from amino acids, lactate, glycerol) |
| ↑ Ketogenesis | Ketone bodies as fuel in fasting |
| ↓ Lipogenesis | Fat synthesis stops |
| ↑ Ureagenesis | Amino acids used for glucose; nitrogen excreted as urea |
| ↑ Lipolysis (at high levels) | More fatty acids |
| ↑ Insulin secretion | Stimulates beta cells (prevents excess glucose rise after protein meals) |
Glucagon is a liver hormone: it raises glucose by glycogenolysis and gluconeogenesis and increases ketogenesis.
Fed and fasting states
| Fed (insulin high) | Fasting (glucagon high, insulin low) |
|---|---|
| Glucose stored as glycogen and fat | Glycogen broken down |
| Protein synthesis | Gluconeogenesis from amino acids |
| Fat stored | Fat broken down; ketones made |
| K+ moves into cells |
Clinical relevance
Type 1 diabetes
How it happens: autoimmune destruction of beta cells; absolute insulin deficiency.
What you see: high glucose, weight loss, thirst, polyuria; risk of diabetic ketoacidosis (high glucagon and no insulin → uncontrolled lipolysis and ketogenesis).
Type 2 diabetes
How it happens: insulin resistance (obesity, inactivity) with failing beta cells.
What you see: high glucose, often found on screening; ketoacidosis is uncommon.
Diabetic ketoacidosis
High glucose with osmotic diuresis and dehydration, ketones, high anion gap metabolic acidosis, deep sighing breathing and a raised or normal plasma K+ despite a total body K+ deficit.
Hypoglycaemia
How it happens: too much insulin or sulfonylurea, missed meals, alcohol, insulinoma.
What you see: sweating, tremor, palpitations (adrenaline) and confusion, fits and coma (brain glucose shortage).
Expect: islet cell types, the steps of glucose-stimulated insulin secretion and sulfonylurea action, C-peptide, insulin's actions on carbohydrate, fat, protein and potassium, insulin-dependent tissues (muscle and fat via GLUT4) vs independent (brain, liver, red cells), and glucagon's hepatic actions.
Quick revision
- Beta: insulin; alpha: glucagon; delta: somatostatin.
- GLUT2 → ATP → KATP closes → depolarisation → Ca2+ → insulin.
- Insulin: ↓ glucose, ↑ glycogen, fat and protein storage, K+ into cells.
- GLUT4 (insulin-dependent): resting muscle and fat. Brain, red cells, liver: insulin-independent.
- Insulin activates liver glucokinase.
- Glucagon (liver, cAMP): ↑ glycogenolysis, gluconeogenesis, ketogenesis, ureagenesis; ↓ lipogenesis.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
Which tissues need insulin for glucose uptake?
Resting skeletal muscle and adipose tissue, which use the GLUT4 transporter.
How does insulin affect potassium?
It moves potassium into cells by stimulating the sodium-potassium pump, lowering plasma potassium.
What are the actions of glucagon on the liver?
It increases glycogenolysis, gluconeogenesis, ketogenesis and urea formation and reduces fat synthesis.
What is C-peptide?
The fragment cut from proinsulin when insulin is made; it shows how much insulin the pancreas itself is producing.