Glucagon 

  • Author: Cory Wilczynski, MD; Chief Editor: Eric B Staros, MD  more...
 
Updated: Dec 10, 2013
 

Reference Range

Glucagon is a peptide compromised of 29 amino acids in a single chain. It is produced by the alpha-cells in the exocrine pancreas and secreted by the liver and the kidneys, with a half-life of 3-6 minutes. Because of this rapid inactivation, collection of serum glucagon needs to occur in a chilled collecting tube with the immediate addition of a proteolytic enzyme inhibitor.

The reference ranges for glucagon can be found in the table below.[1]

Table 1. Glucagon Reference Ranges

Table. (Open Table in a new window)

TestSourceAges, conditions, etc.Conventional UnitsConversion FactorSI UnitsComments
GlucagonPlasmaAdult< 60 pg/mL0.287< 17.2 pmol/LCentrifuge immediately under refrigeration. Store in plastic vial with 0.5 ml aprotinin (10,000KIU/mL) at -20°C. An overnight fast is required.
Children
Cord blood< 215 pg/mL< 62 pmol/L
Day 1< 240 pg/mL< 69 pmol/L
Day 2< 400 pg/mL< 115 pmol/L
Day 3< 420 pg/mL< 121 pmol/L
Day 4-14< 148pg/mL< 42 pmol/L

See the list below:

  • For basic reference the interval in adults/children is 40-130 ng/L.[2]
  • Blood glucose levels are measured in mg/dL.
  • Hypoglycemia is considered when glucose value is less than 70mg/dL.
  • The normal glucose range is 80-100 mg/dL.
  • Prediabetes is 100-126 mg/dL.
  • Diabetes after a fasting study is greater than 126mg/dL.
  • Diabetes are a nonfasting study is greater than 200mg/dL.
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Interpretation

Glucagon works along with insulin to balance glucose distribution in the serum for transport to body tissues. The serum level of glucose is the driving force on which these 2 hormones are either being activated or inhibited. Insulin stimulates glucose and amino acid uptake from the blood to tissues for functional use. This is why during a meal glucose levels will initially rise due to the intake, but, in normal healthy subjects, insulin’s job is to bring the levels back down to normal limits. For diabetics, we see the result of the lack of this hormone especially after a meal in which glucose values will elevate extremely high unless any endogenous insulin can inhibit glucagon’s effect for producing more glucose through the process of glycogenolysis.[3]

Normal levels of fasting glucose (80-100 mg/dL) mean that a balance exists and that both insulin and glucagon are adequately produced. Abnormalities in glucose levels are the most common reason to measure glucagon levels in serum to see if the hormone is the source versus insulin levels, which tend to be more difficult to interpret.

A condition associated with elevated glucagon, a glucagonoma, usually has levels a 1000-fold greater than normal. These tumors are pancreatic in origin and have symptoms including necrolytic migratory erythema, hyperglycemia, and reduced amino acids. Another condition that includes glucagonoma includes multiple endocrine neoplasia type 1. The 3 tumors of this syndrome include the parathyroid glands, the pancreas, and the anterior pituitary gland.[5]

Similarly, low levels of glucagon are seen when patient is having hypoglycemia (blood glucose less than 70mg/dL). Patient will experience autonomic dysfunction (shaking, palpitations, sweating, nervousness) and central nervous system dysfunction (confusion, unresponsiveness, seizures). Persistent hypoglycemia can be associated with an insulinoma, overmedication of insulin or oral hypoglycemia drugs, or prolonged fasting.

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Collection and Panels

See the list below:

  • Collect in lavender (EDTA) or pink (K2EDTA) plus aprotinin tube. Collect in chilled container.[2]
  • Condition: Fasting[2]
  • Storage/transport temperature: Critical frozen. Separate specimens must be submitted when multiple tests are ordered.[2]
  • Unacceptable conditions: Specimens transported in glass tubes.[2]

Stability (collection to initiation of testing; after separation from cells) is as follows:

  • Ambient - Unacceptable
  • Refrigerated - Unacceptable
  • Frozen - 3 months[2]
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Background

Glucagon is a peptide compromised of 29 amino acids in a single chain. It is produced by the alpha-cells in the exocrine pancreas and secreted by the liver and the kidneys, with a half-life of 3-6 minutes. Because of this rapid inactivation, collection of serum glucagon needs to occur in a chilled collecting tube with the immediate addition of a proteolytic enzyme inhibitor. Glucagon is an initial precursor in the metabolism of glucose increasing cAMP, gluconeogenesis, and ketogenesis. Glucagon works against the anabolic effects of insulin to catabolize glycogen. The result of this is variable on the tissue glucagon works in as can be seen in Table 2. For example, in cardiac tissue, glucagon is a potent inotropic and chronotropic effect mediated by cAMP; in the small intestine, glucagon has been known to relax the smooth muscle in large amounts.[6]

The most important clinical use of glucagon is a drug in its recombinant form that is used for treatment of severe hypoglycemic reactions in diabetes. A glucagon pen or GlucaPen contains 1 mg of the recombinant hormone that should be injected intramuscularly when oral feedings are not possible or patients are completely unresponsive. Glucagon is also sometimes useful for reversing the cardiac effects of a beta-blocker overdose.[6]

Table 2: Metabolic Actions of Insulin and Glucagon [3]

Table. (Open Table in a new window)

Fatty acid uptake and release in fatInsulinStimulates synthesis of triglycerides (TG) from free fatty acids (FFA); inhibits release of FFA from TG .
GlucagonStimulates release of FFA from TG.
Liver glycogenInsulinIncreases synthesis and thereby glucose uptake and storage.
GlucagonStimulates glycogenolysis and glucose release.
Liver gluconeogenesisInsulinInhibits, saves amino acids.
GlucagonStimulates, glucose synthesized and released.
Glucose uptake, skeletal muscleInsulinStimulates uptake, storage as glycogen and use in energy metabolism.
GlucagonNo receptors, no effect.
Glycogen, skeletal muscleInsulinStimulates synthesis.
GlucagonNo receptors, no effect.
Amino acid uptakeInsulinStimulates and is necessary for protein synthesis.
GlucagonNo receptors, no effect.
Brain (hypothalamus)InsulinReduces hunger through hypothalamic regulation.
GlucagonNo effect.
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Contributor Information and Disclosures
Author

Cory Wilczynski, MD Fellow, Department of Endocrinology, Loyola Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital

Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology

Disclosure: Nothing to disclose.

References
  1. Gardner DG, Shoback D. Appendix: Normal Hormone Reference Ranges. Gardner DG, Shoback D, eds. Greenspan’s Basic & Clinical Endocrinology. 9th ed. New York: McGraw-Hill; 2011. [Full Text].

  2. Glucagon. ARUP Lab Tests. ARUP Laboratories: National Reference Laboratories. Available at http://www.aruplab.com. Accessed: 2006-2012.

  3. Horn S. Insulin and Glucagon. MedBio.info. 2011 . Available atAccessed April 22, 2012. Available at http://www.medbio.info/.

  4. Horn S. Insulin and Glucagon. MedBio.info. 2011. Available at http://www.medbio.info/. Accessed: April 22, 2012.

  5. Glycogen Metabolism and Glycogen storage Diseases. Medchrome: Medical Health and Articles. 2011. Available at http://medchrome.com/medicalcolleges/student-life/glycogen-metabolism-and-glycogen-storage-diseases. Accessed: April 21, 2012.

  6. Kloppel G., Komminoth P., Perren A., et. al. Glucagonoma." In DeLellis RA, Lloyd RV, Heitz P, Eng C eds. World Health Organizaiton of Tumours: Pathology and Genetics of Tumours of Endocrine Pancreas. IARC Press: Lyon. 2004.

  7. Nolte Kennedy MS. Pancreatic Hormones & Antidiabetic Drugs. Katzung BG, Masters SB, Trevor AJ, eds. Basic & Clinical Pharmacology. 12nd ed. New York: McGraw-Hill; 2012. Chapter 41. [Full Text].

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Table.
TestSourceAges, conditions, etc.Conventional UnitsConversion FactorSI UnitsComments
GlucagonPlasmaAdult< 60 pg/mL0.287< 17.2 pmol/LCentrifuge immediately under refrigeration. Store in plastic vial with 0.5 ml aprotinin (10,000KIU/mL) at -20°C. An overnight fast is required.
Children
Cord blood< 215 pg/mL< 62 pmol/L
Day 1< 240 pg/mL< 69 pmol/L
Day 2< 400 pg/mL< 115 pmol/L
Day 3< 420 pg/mL< 121 pmol/L
Day 4-14< 148pg/mL< 42 pmol/L
Table.
Fatty acid uptake and release in fatInsulinStimulates synthesis of triglycerides (TG) from free fatty acids (FFA); inhibits release of FFA from TG .
GlucagonStimulates release of FFA from TG.
Liver glycogenInsulinIncreases synthesis and thereby glucose uptake and storage.
GlucagonStimulates glycogenolysis and glucose release.
Liver gluconeogenesisInsulinInhibits, saves amino acids.
GlucagonStimulates, glucose synthesized and released.
Glucose uptake, skeletal muscleInsulinStimulates uptake, storage as glycogen and use in energy metabolism.
GlucagonNo receptors, no effect.
Glycogen, skeletal muscleInsulinStimulates synthesis.
GlucagonNo receptors, no effect.
Amino acid uptakeInsulinStimulates and is necessary for protein synthesis.
GlucagonNo receptors, no effect.
Brain (hypothalamus)InsulinReduces hunger through hypothalamic regulation.
GlucagonNo effect.
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