Results obtained with different glucagon assays can differ substantially. This can be caused by use of different calibration standards. Different glucagon assays may also exhibit variable cross-reactivity with different isoforms of glucagon, not all of which are biologically active. Some assays, including this one, remove biologically inactive isoforms before measurement, while others do not. All these factors contribute to the differences between different assays. Therefore, serial measurements should always be performed using the same assay.
The heterogeneity of plasma glucagon is well established. It has at least 3 major components. In addition to the biologically active glucagon (MW 3500) and its possible precursor (MW 9000), there also is big plasma glucagon (BGP) of unknown biological significance. By using ethanol extraction, BPG (considered to be an interfering factor in the glucagon assay) is removed. Therefore, the assay measures only biologically active glucagon and its precursors.
Precise reference ranges for appropriate glucagon responses for given blood glucose ranges are not well established and vary widely from assay to assay. Expert advice should be sought when interpreting inappropriately low glucagon levels or when interpreting glucagon, insulin, and C-peptide levels obtained during mixed-meal testing.
Diabetics, obese subjects, acromegalics, and patients with Cushing syndrome have higher glucagon levels.
Tumor marker tests, including glucagon, are not specific for malignancy. All immunometric assays can, on rare occasions, be subject to hooking at extremely high analyte concentrations (false-low results), heterophilic antibody interference (false-high results), or autoantibody interference (unpredictable effects). If the laboratory result does not fit the clinical picture, these possibilities should be considered.
Glucagon is a single-chain polypeptide of 29 amino acids that is derived from a larger precursor peptide (big plasma glucagon) that is cleaved upon secretion. The main sites of glucagon production are the hypothalamus and pancreatic alpha-islet cells. The function of hypothalamic glucagon is incompletely understood and currently no clinical disorders of hypothalamic glucagon function have been defined. Pancreatic islet glucagon is secreted in response to hypoglycemia, with resultant increases in blood glucose concentration. Glucagon's hyperglycemic effect is produced by stimulating hepatic glycogenolysis and gluconeogenesis; it has no effect on muscle glycogen. Once blood glucose levels have normalized, glucagon secretion ceases.
Excessive glucagon secretion can lead to hyperglycemia. Excessive and inappropriate glucagon secretion can sometimes be observed in diabetes, in particular during ketoacidosis, and can complicate management of the disorder. In rare cases, it also can occur in tumors of the pancreatic islets (glucagonoma), carcinoid tumors and other neuroendocrine neoplasms, and hepatocellular carcinomas. Patients with glucagon-secreting tumors may present with classic glucagonoma syndrome, consisting of necrolytic migratory erythema, diabetes, and diarrhea but can also have more subtle symptoms and signs.
Decreased or absent glucagon response to hypoglycemia can be seen in type I diabetes (insulin-dependent diabetes) and can contribute to severe and prolonged hypoglycemic responses.
Glucagon is routinely measured along with serum glucose, insulin, and C-peptide levels, during the mixed-meal test employed in the diagnostic workup of suspected postprandial hypoglycemia. However, it plays only a minor role in the interpretation of this test.