Glucagon is a peptide hormone that originates in the α cells of the pancreatic islets of Langerhans. This hormone promotes glucose production in the liver. Normally, glucagon is a counterbalance to insulin. Glucagon provides a sensitive, coordinated control mechanism for glucose production and storage. For example, low blood glucose levels cause glucagon to stimulate glucose release into the bloodstream, whereas elevated blood glucose levels reduce the amount of circulating glucagon to about 50% of that found in the fasting state. The kidneys also affect glucagon metabolism. Elevated fasting glucagon levels in the presence of end-stage kidney disease return to normal levels following successful kidney transplantation. Abnormally high glucagon levels drop toward normal once insulin therapy effectively controls diabetes. However, when compared with a healthy person, glucagon secretion in the person with diabetes does not decrease after eating carbohydrates. Moreover, in healthy persons, arginine infusion causes increased glucagon secretion.

This test measures glucagon production and metabolism. A glucagon deficiency reflects pancreatic tissue loss. Failure of glucagon levels to rise during arginine infusion confirms glucagon deficiency. Hyperglucagonemia (i.e., elevated glucagon levels) occurs in diabetes, acute pancreatitis, and situations in which catecholamine secretion is stimulated (e.g., pheochromocytoma, infection).

Adults and children: ≤80 pg/mL or ≤80 ng/L

Newborns (up to 4 days): 100–650 pg/mL or 100–650 ng/L

Normal ranges vary with different laboratories.

1. Draw a 5-mL blood sample from a fasting person into a chilled EDTA Vacutainer tube containing aprotinin proteinase inhibitor. Special handling is required because glucagon is very prone to enzymatic degradation. Tubes used to draw blood must be chilled before the sample is collected and placed on ice afterward, and plasma must be frozen as soon as possible after centrifuging.

2. Observe standard precautions. Label the specimen with the patient’s name, date and time of collection, and test(s) ordered. Place the specimen in a biohazard bag.

1. Increased glucagon levels are associated with the following conditions:

   1. Acute pancreatitis (e.g., pancreatic α-cell tumor)

   2. Diabetes: Persons with severe diabetic ketoacidosis are reported to have fasting glucagon levels five times normal despite marked hyperglycemia

   3. Glucagonoma (familial), which may be manifested by three different syndromes:

      1. The first syndrome exhibits a characteristic skin rash, necrolytic migratory erythema, diabetes or IGT, weight loss, anemia, and venous thrombosis. This form usually shows elevated glucagon levels (>1000 pg/mL or >1000 ng/L) (diagnostic).

      2. The second syndrome occurs with severe diabetes.

      3. The third form is associated with multiple endocrine neoplasia syndrome and can show relatively lower glucagon levels as compared with the others.

   4. CKD

   5. Hyperlipidemia

   6. Stress (trauma, burns, surgery)

   7. Uremia

   8. Hepatic cirrhosis

   9. Hyperosmolality

   10. Acute pancreatitis

   11. Hypoglycemia

2. Reduced levels of glucagon are associated with the following conditions:

   1. Loss of pancreatic tissue

      1. Pancreatic neoplasms

      2. Pancreatectomy

   2. Chronic pancreatitis

   3. Cystic fibrosis