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Glucagon

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CONVENTIONAL UNITS

(Pancreatic α-Cell Hormone – Key Regulator of Glucose Homeostasis & Counter-Regulatory Response)

Synonyms

  • Glucagon
  • Pancreatic α-cell hormone
  • Hyperglycemic hormone
  • Counter-regulatory hormone
  • Immunoreactive glucagon (IRG)

Units of Measurement

  • ng/L
  • ng/dL
  • ng/100 mL
  • ng%
  • pg/mL

Key Conversions

(Molecular weight ≈ 3485 Da)

1 pg/mL = 1 ng/L
1 ng/dL = 10 pg/mL = 10 ng/L
ng/100 mL = ng% = ng/dL
1 ng/L = 1 pg/mL

(Glucagon is measured in mass units, not activity units.)

Description

Glucagon is a 29-amino-acid peptide hormone produced by pancreatic alpha cells.

It is the primary counter-regulatory hormone to insulin, maintaining glucose during fasting by:

  • Stimulating hepatic glycogenolysis
  • Increasing gluconeogenesis
  • Promoting ketogenesis
  • Increasing lipolysis

Glucagon secretion rises during:

  • Hypoglycemia
  • Exercise
  • Stress
  • Amino-acid ingestion
  • Sympathetic activation

Physiological Role

1. Glucose Regulation

Glucagon increases plasma glucose by:

  • Breaking glycogen → glucose
  • Stimulating hepatic glucose output
  • Opposing insulin action

2. Ketone Production

Stimulates ketogenesis during fasting/starvation.

3. Protein Metabolism

Amino-acid ingestion strongly stimulates glucagon.

4. Stress Response

Increases during acute illness, trauma, and exercise.

Clinical Significance

High Glucagon (Hyperglucagonemia)

1. Glucagonoma

Rare α-cell neuroendocrine tumor → excessively high glucagon.

Classic symptoms:

  • Necrolytic migratory erythema
  • Diabetes / hyperglycemia
  • Weight loss
  • Anemia
  • Diarrhea

Very high glucagon (>500–1000 pg/mL) strongly suggests glucagonoma.

2. Diabetes Mellitus

  • Inappropriately elevated fasting & postprandial glucagon
  • Contributes to hyperglycemia

3. Acute Illness / Stress

  • Sepsis
  • Burns
  • Trauma
  • Surgery

4. Chronic Kidney Disease

Reduced clearance → elevated glucagon.

5. Cirrhosis & Liver Disease

Impaired metabolism → higher glucagon.

Low Glucagon

Seen in:

  • Hypothalamic/pancreatic failure
  • Advanced pancreatitis
  • Post-total pancreatectomy
  • Genetic α-cell dysfunction
  • Severe hypoglycemia from insulinoma
  • Exogenous insulin overdose (impaired glucagon response)

Low glucagon can worsen severe hypoglycemia.

Reference Intervals

(Tietz 8E + Mayo + ARUP)
Values depend on fasting state and assay type.

Fasting Glucagon

  • 50 – 150 pg/mL
    (= 50 – 150 ng/L)

Postprandial

  • Mild rise to 150–200 pg/mL

Glucagonoma

  • >500 pg/mL
  • Often >1000 pg/mL

Diagnostic Uses

1. Diagnosis of Glucagonoma

  • Markedly elevated glucagon
  • Imaging: CT/MRI/Octreoscan
  • Clinical symptoms

2. Hypoglycemia Evaluation

Low glucagon response suggests:

  • Insulinoma
  • Pancreatic failure
  • Insulin overdose

3. Diabetes Pathophysiology

Abnormal glucagon secretion contributes to:

  • Fasting hyperglycemia
  • Post-meal hyperglycemia

4. Assessment in Acute Illness

Stress-induced hyperglucagonemia correlates with severity.

5. Research Use

  • Studies of insulin–glucagon axis
  • Ketogenic diet monitoring
  • Metabolic disease research

Analytical Notes

  • Fasting sample required (8–10 hours)
  • Place sample on ice immediately
  • Use EDTA tube + aprotinin (to prevent degradation)
  • Plasma preferred over serum
  • Highly assay-dependent (interpret with lab reference range)
  • Hemolysis and delayed processing falsely decrease glucagon

Clinical Pearls

  • Glucagon is the first line of defense against hypoglycemia.
  • In diabetes, glucagon is inappropriately high even after meals.
  • Glucagonoma is rare but presents with a characteristic rash (NME).
  • CKD elevates glucagon due to reduced clearance.
  • During severe hypoglycemia, glucagon release may be impaired in long-standing diabetes.

Interesting Fact

The first glucagon radioimmunoassay in the 1950s revolutionized understanding of glucose homeostasis and paved the way for modern diabetes physiology research.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Hormones.
  2. Endocrine Society Guidelines - Hypoglycemia & Neuroendocrine Tumors.
  3. ADA Standards - Diabetes Physiology.
  4. Mayo Clinic Laboratories - Glucagon.
  5. ARUP Consult - Glucagonoma Evaluation.
  6. MedlinePlus / NIH - Glucagon Test.

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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