Glucagon is a hormone secreted by the alpha cells of the pancreatic islets of Langerhans. Glucagon is secreted in response to hypoglycemia and increases the blood glucose by breaking down glycogen to glucose in the liver. It also increases glucose in other tissues by inhibiting passage of glucose into cells and by encouraging efflux of glucose from the cell. Glucagon also oxidizes fatty acids to their basic glycerol components to form glucose. As serum glucose levels rise in the blood, glucagon is inhibited by a negative feedback mechanism.
Direct measurement of glucagon in the blood is used to diagnose a glucagonoma. It is also useful in the evaluation of some diabetic patients. Also, pancreatic function can be investigated with the direct measurement of glucagon.
Elevated glucagon levels may indicate the diagnosis of a glucagonoma (i.e., an alpha islet cell neoplasm). Glucagon deficiency occurs with extensive pancreatic resection or with burned-out pancreatitis. Arginine is a potent stimulator of glucagon. If the glucagon levels fail to rise even with arginine infusion, the diagnosis of glucagon deficiency as a result of pancreatic insufficiency is confirmed.
Normally glucagon decreases after ingestion of a carbohydrate-loaded meal through an elaborate negative feedback mechanism. This does not occur in patients with diabetes. Furthermore, in the insulin-dependent diabetic, glucagon stimulation caused by hypoglycemia does not occur. Arginine stimulation is performed to differentiate pancreatic insufficiency and diabetes. The diabetic will have an exaggerated elevation of glucagon with arginine administration. In pancreatic insufficiency, glucagon is not stimulated with arginine. In diabetic patients, hypoglycemia fails to stimulate glucagon release, as occurs in a nondiabetic person.
Because glucagon is thought to be metabolized by the kidneys, renal failure is associated with high glucagon levels and, as a result, high glucose levels. When rejection of a transplanted kidney occurs, one of the first signs of rejection may be increased serum glucose levels.
Before measuring Glucagon, the patient is required to fast for 10 to 12 hours. Only water is permitted.
Causes of False Glucagon Measurement
Test results may be invalidated if a patient has undergone a radioactive scan within the previous 48 hours and glucagon is measured by radioimmunoassay (RIA). Administration of radionuclides can affect results.
Glucagon levels may be elevated after prolonged fasting, stress, or moderate to intense exercise.
Drugs that may cause increased Glucagon levels include some amino acids (e.g., arginine), cholecystokinin, danazol, gastrin, glucocorticoids insulin, nifedipine, and sympathomimetic amines.
Drugs that may cause decreased Glucagon levels include atenolol, propranolol, and secretin.
Normal Glucagon Levels
The normal Glucagon level is between 50 to 100 ng/L (Nanograms per Liter)
Causes of High Glucagon Levels
Familial hyperglucagonemia: There is a genetic defect that causes a predominance of a glucagon precursor.
Glucagonoma: There are several syndromes, including the more common multiple endocrine neoplasia, that are associated with glucagonomas.
Diabetes mellitus (DM): The pathophysiology of this observation is not known.
Chronic renal failure: Glucagon is metabolized by the kidney. With loss of that function, glucagon and glucose levels rise.
Severe stress, including infection, burns, surgery, and acute hypoglycemia: Stress stimulates catecholamine release. This in turn stimulates glucagon secretion.
Acromegaly: Growth hormone is a stimulator of glucagon.
Hyperlipidemia: The pathophysiology of this observation is not well established.
Acute pancreatitis: The contents of the pancreatic cells (including glucagon) are spilled into the bloodstream as they are injured during the inflammation.
Pheochromocytoma: Catecholamines are potent stimulators to glucagon secretion.
Causes of Low Glucagon Levels
Idiopathic glucagon deficiency: The pathophysiology of this process is not well understood. An autoantibody process may be the cause.
Chronic pancreatitis: The chronically diseased pancreas cannot produce glucagon.
Postpancreatectomy: In the absence of pancreatic tissue, glucagon secretion will not occur.
Cancer of pancreas: Pancreatic tissue destroyed by tumor will not secrete glucagon.