Glucagon, Plasma

CPT: 82943
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Test Details

Synonyms

  • Pancreatic Glucagon

Use

For use (1) when considering a glucagon-secreting tumor of the pancreas, (2) in the diagnosis and management of diabetes mellitus and other carbohydrate metabolism disorders, and (3) in the diagnosis of glucagon deficiency in patients with hypoglycemia.

Limitations

The Millipore glucagon RIA kit employed by LabCorp has been shown to exhibit a small cross-reactivity with oxyntomodulin and glicentin.1

Results of this test are labeled for research purposes only by the assay's manufacturer. The performance characteristics of this assay have not been established by the manufacturer. The result should not be used for treatment or for diagnostic purposes without confirmation of the diagnosis by another medically established diagnostic product or procedure. The performance characteristics were determined by LabCorp.

Methodology

Radioimmunoassay (RIA)

Reference Interval

50−150 pg/mL

Additional Information

Glucagon is produced by the alpha cells of the islets of Langerhans of the pancreas in response to a decrease in plasma glucose concentrations and in response to increased concentrations of specific amino acids.2 The glucagon precursor protein undergoes tissue-specific post-translation processing.2 Glucagon secretion is controlled by a number of factors. In nondiabetic individuals, secretion is stimulated by protein-rich meals, but inhibited by carbohydrate-rich meals. Hypoglycemia activates the autonomic nervous system which stimulates glucagon release into the portal circulation.3-5 Glucagon release is also regulated in a paracine manner by insulin, zinc and other factors secreted from neighboring β- and δ-cells within the islet of Langerhans.5 In healthy individuals, glucagon released is inhibited by hyperglycemia, mixed nutrient meals, and oral intravenously administered amino acids.

Glucagon is a counter-regulatory hormone opposing the actions of insulin in glucose homoeostasis. The intravenous administration of glucagon raises blood glucose substantially in nondiabetic individuals.6 Glucagon is thought to play an important role in the maintenance of fasting and postprandial glucose homeostasis.6,7 By stimulating hepatic glucose output, glucagon counterbalances the action of insulin and serves to maintain circulating glucose and prevent insulin mediated hypoglycemia.2,5 Blockade of endogenous glucagon secretion with somatostatin causes glucose concentrations to decrease.6

A highly specific glucagon receptor is abundantly expressed on hepatocytes.6 Glucagon binding to this receptor leads to increased hepatic glucose production, fatty acid oxidation and ketogenesis.6,7 Glucagon stimulates glycogenolysis and gluconeogenesis, changing the liver from an organ of glucose release.2,3 Glucagon secretion inhibits gastric emptying, increases gastric output, increases bile flow and increases cardiac muscle contraction. Glucagon also has lipolytic effects.2

Insulin treatment of diabetic patients can cause acute hypoglycemia which is often exacerbated by a deficient glucagon response.3,4,6,8,9 The exact pathophysiologic mechanisms for this dysregulation is not fully defined but has been attributed, in part, to a lack of intra-islet insulin effect.5,10

Alternatively, some patients with controlled type 1 diabetes experience inappropriately elevated plasma glucagon levels in the context of hyperglycemia.6 Both type 1 and type 2 diabetes frequently exhibit an inappropriately high glucagon response to a meal.10 The high levels of glucagon have been shown to contribute importantly to diabetic hyperglycemia and can result in ketoacidosis.3-7,11 Relative hyperglucagonemia, in the setting of deficient insulin secretion may contribute to the development of fasting and postprandial hyperglycemia in the patients.6-8

Increased plasma glucagon levels have been demonstrated in many forms of physiological stress that are not typically associated with hypoglycemia.9 Hyperglucagonemia has been documented in patients with trauma, burns, surgery, sepsis, hemorrhage, acute myocardial infarction, cardiac arrest and neonatal hypoxia.9

A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in up to a 1000-fold overproduction of glucagon.12,13 Serum glucagon concentrations in excess of 500 pg/mL are strongly suggestive of glucagonoma.12 These tumors are associated with glucagonoma syndrome. The raised glucagon concentrations produce hyperglycemia, diabetes mellitus and glucose intolerance. Excessive glucagon action produces a catabolic state resulting in weight loss.2,14 Glucagonomas frequently present with a specific dermatitis referred to as necrolytic migratory erythema (NME).15 Patients with NME develop erythematous blisters and swelling in areas subject to greater friction and pressure, including the lower abdomen, buttocks, perineum, and groin.1,13 In addition, these patients are prone to deep venous thrombosis that may be a significant cause of death. Other common symptoms of glucagonoma include depression,diarrhea and anemia.2,12,14 Because the symptoms of early disease are nonspecific, patients often present at a later stage with extensive metastatic disease.2

Specimen Requirements

Specimen

Plasma with Trasylol®, frozen

Volume

1 mL

Minimum Volume

0.5 mL (Note: This volume does not allow for repeat testing.)

Container

Lavender-top (EDTA) tube (chilled)

Patient Preparation

Overnight fasting for basal levels. No isotopes administered 24 hours prior to venipuncture. Patient should not be in a stress state at time of drawing. If diabetic, patient should be in good control before specimen is drawn.

Collection

Trasylol® kits may be ordered through the PeopleSoft system (LabCorp N° 33328). Using a chilled 6-mL lavender-top (EDTA) tube taken from the kit, collect a whole blood specimen. Mix the specimen several times by inverting the EDTA collection tube. After removing the cap from the EDTA draw tube, take one of the sterile, Beral pipettes (from under the gray foam), and add 0.25 mL Trasylol® to the EDTA tube. Recap the EDTA tube and invert several times to mix well. Centrifuge the EDTA tube to separate the plasma from the cells, and immediately transfer the plasma into one of the brown screw-cap transfer tubes provided in the kit. There should be a "Trasylol® Added" label affixed to the brown transfer tubes. Cap and freeze the labeled transfer tube containing the EDTA plasma with Trasylol® added. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.

Storage Instructions

Freeze.

Stability Requirements

Temperature

Period

Room temperature

7 days

Refrigerated

7 days

Frozen

7 days

Freeze/thaw cycles

Stable x1

Causes for Rejection

Sample not collected with Trasylol®; sample not submitted in tube with Trasylol label, gross hemolysis; recently administered radioisotopes; specimen not received frozen; serum, sodium citrate, or heparinized plasma specimen; lipemia

Clinical Information

Special Instructions

Contact the LabCorp supply department for collection kit.

Footnotes

1. Bak MJ, Albrechtsen NW, Pedersen J, et al. Specificity and sensitivity of commercially available assays for glucagon and oxyntomodulin measurement in humans. Eur J Endocrinol. 2014 Mar 8; 170(4):529-538. 24412928
2. Ardill JE. Circulating markers for endocrine tumours of the gastroenteropancreatic tract. Ann Clin Biochem. 2008 Nov; 45(Pt 6):539-559. 18941127
3. Jiang G, Zhang BB. Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab. 2003 Apr; 284(4):E671-E678. 12626323
4. Taborsky GJ Jr, Mundinger TO. Minireview: The role of the autonomic nervous system in mediating the glucagon response to hypoglycemia. Endocrinology. 2012 Mar; 153(3):1055-1062. 22315452
5. Gromada J, Franklin I, Wollheim CB. Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev. 2007 Feb; 28(1):84-116. 17261637
6. D'Alessio D. The role of dysregulated glucagon secretion in type 2 diabetes. Diabetes Obes Metab. 2011 Oct; 13(Suppl 1):126-132. 21824266
7. Cryer PE. Glucagon in the pathogenesis of hypoglycemia and hyperglycemia in diabetes. Endocrinology. 2012 Mar; 153(3):1039-1048. 22166985
8. Holst JJ, Christensen M, Lund A, et al. Regulation of glucagon secretion by incretins. Diabetes Obes Metab. 2011 Oct; 13(Suppl 1):89-94. 21824261
9. Jones BJ, Tan T, Bloom SR. Minireview: Glucagon in stress and energy homeostasis. Endocrinology. 2012 Mar; 153(3):1049-1054. 22294753
10. Brown RJ, Sinaii N, Rother KI. Too much glucagon, too little insulin: time course of pancreatic islet dysfunction in new-onset type 1 diabetes. Diabetes Care. 2008 Jul; 31(7):1403-1404. 18594062
11. Shah P, Vella A, Basu A, Basu R, Schwenk WF, Rizza RA. Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2000 Nov; 85(11):4053-4059. 11095432
12. Ito T, Igarashi H, Jensen RT. Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical treatment: advances. Best Pract Res Clin Gastroenterol. 2012 Dec; 26(6):737-753. 23582916
13. Kindmark H, Sundin A, Granberg D, et al. Endocrine pancreatic tumors with glucagon hypersecretion: A retrospective study of 23 cases during 20 years. Med Oncol. 2007; 24(3):330-337. 17873310
14. Eldor R, Glaser B, Fraenkel M, Doviner V, Salmon A, Gross DJ. Glucagonoma and the glucagonoma syndrome—cumulative experience with an elusive endocrine tumour. Clin Endocrinol (Oxf). 2011 May; 74(5):593-598. 21470282
15. van Beek AP, de Haas ER, van Vloten WA, Lips CJ, Roijers JF, Canninga-van Dijk MR. The glucagonoma syndrome and necrolytic migratory erythema: A clinical review. Eur J Endocrinol. 2004 Nov; 151(5):531-537. 15538929

References

Bataille D, Blache P, Mercier F, et al. Glucagon and related peptides: Molecular structure and biological specificity. Ann N Y Acad Sci. 1988; 527:168-185 (review). 3291691
Boden G. Glucagonomas and insulinomas. Gastroenterol Clin North Am. 1990; 18(4):831-845. 2559035
Diagnostic Products Corporation. Glucagon Double Antibody. [package insert] Los Angeles, Calif: DPC;1998.
Diem P, Redmon JB, Abid M, et al. Glucagon, catecholamine, and pancreatic polypeptide secretion in type I diabetic recipients of pancreas allografts. J Clin Invest. 1990; 86(6):2008-2013. 2254456
Fraker DL, Norton JA. The role of surgery in the management of islet cell tumors. Gastroenterol Clin North Am. 1989; 18(4):805-830. 2559034
Liu D, Moberg E, Kollind M, et al. A high concentration of circulating insulin suppresses the glucagon response to hypoglycemia in normal man. J Clin Endocrinol Metab. 1991; 73(5):1123-128. 1682339
Rothe AJ, Young JW, Keramati B, et al. The value of glucagon in routine barium investigations of the gastrointestinal tract. Invest Radiol. 1987; 22(10):786-791. 3429174

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
004622 Glucagon, Plasma 2338-2 004622 Glucagon, Plasma pg/mL 2338-2
Reflex Table for Glucagon, Plasma
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 004660 Comment: 004660 Comment: N/A

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