Glucagon and the counter-regulatory hormones !
- Regulation
- Exam priority: medium
When glucose falls, glucagon and epinephrine raise it within minutes; cortisol and GH hold it up for hours.
Updated 2026-11-01
Also called: α cell, Defense against hypoglycemia
See it in 3D: Pancreas · Liver
What it is
Counter-regulatory hormones oppose insulin and protect the brain from hypoglycemia. Glucagon from α cells acts almost only on the liver: it releases glucose from glycogen, makes new glucose and, in long fasting, ketones. Epinephrine, cortisol and GH complete the defense on different time scales. The signal pathway (Gs-coupled receptor, cAMP, PKA) is in Biochemistry.
Regulation
- +Hypoglycemia: Main stimulus of α cells.
- +Amino acids (alanine, arginine): Raise glucagon after a protein meal.
- +Sympathetic nerves and epinephrine (β2): Increase glucagon in exercise and stress.
- −Insulin and zinc from neighboring β cells: Paracrine inhibition within the islet.
- −High glucose: Suppresses secretion.
- −Somatostatin: Inhibits α and β cells.
The stepwise defense against hypoglycemia
| Hormone | Glucose at which it responds (approx.) | Speed | Main action |
|---|---|---|---|
| Insulin (falls) | ≈80–85 mg/dL | Minutes | Stops braking hepatic glucose output |
| Glucagon (rises) | ≈65–70 mg/dL | Minutes | Hepatic glycogenolysis and gluconeogenesis |
| Epinephrine (rises) | ≈65–70 mg/dL | Minutes | Glycogenolysis, lipolysis, ↓ insulin; adrenergic symptoms |
| Cortisol and GH (rise) | ≈65–70 mg/dL | Hours | Gluconeogenesis and less peripheral glucose use |
Clinical notes
- Warning symptoms (tremor, sweating, palpitations, hunger) appear near ≈55 mg/dL; below 50 mg/dL neuroglycopenic ones dominate (confusion, seizures).
- Hypoglycemia unawareness: repeated episodes lower the epinephrine threshold and the patient loses the warning symptoms.
- Beta-blockers can mask the adrenergic symptoms of hypoglycemia (not sweating, which is cholinergic).
Test yourself
Think of the answer, then tap the question to see it.
Why doesn't glucagon release glucose from muscle glycogen?
Muscle has no glucagon receptor and no glucose-6-phosphatase; its glycogen is mobilized by epinephrine and used by the muscle itself.
Why does a protein-rich, carbohydrate-free meal stimulate both insulin and glucagon?
Amino acids stimulate both cell types; insulin lets the amino acids be used and glucagon keeps hepatic glucose output going, preventing hypoglycemia.
Why is a patient with long-standing type 1 diabetes more vulnerable to severe hypoglycemia?
The glucagon response to hypoglycemia is lost and, with repeated episodes, the epinephrine response also weakens; the fast defenses are gone.
Why can't cortisol and GH correct acute hypoglycemia?
They act through changes in gene expression and peripheral metabolism; their effect takes hours, useful in prolonged fasting but not within minutes.
See it in 3D
The structures of Durgical's 3D anatomy where it happens.
Related topics
- Islets and insulin: secretion and actions
- The physiological response to hypoglycemia
- Physiology of diabetes and ketoacidosis
- Actions of cortisol
- The adrenal medulla and catecholamines
- Fed and fasting states: the hormonal switch
Related conditions
In Biochemistry
In Pharmacology
Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.
Sources: 17.9 The Endocrine Pancreas (OpenStax (Rice University), 2022); Hypoglycemia: MedlinePlus (MedlinePlus, US National Library of Medicine, 2024); Type 1 Diabetes (StatPearls (NCBI Bookshelf), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 79). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).
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Representative model, for educational purposes only.