Glucagon and Hypoglycemia: Hormonal Control of Blood Sugar
What Is Glucagon?
Many people have heard of insulin, a hormone made by the pancreas that lowers the blood sugar level and that people with type 1 diabetes lack. There is another pancreatic hormone that also has an important effect on blood sugar, however. This hormone is glucagon. Glucagon has the opposite effect to insulin. It raises the blood sugar level instead of lowering it.
Glucose (blood sugar) is obtained from the food that we digest. The glucose enters our blood through the lining of the small intestine and is used as an energy source by our cells. The concentration of glucose in the blood is affected by the frequency of eating, the amount and types of food that we eat, the amount of exercise that we perform, the use of certain medications, and other factors. Insulin and glucagon work to keep the glucose level in the blood constant, which is very important for the functioning of the brain.
The brain requires a continuous supply of glucose. A glucose level that is too low or too high can both be dangerous in the body. However, a very low blood sugar level will have an immediate effect on the brain while the effects of continually high blood sugar take longer to develop.
The Pancreas and Its Functions
Role of the Pancreas and Liver in Controlling Blood Sugar
Both the pancreas and the liver play a role in controlling blood sugar. Glucagon and insulin are made in a part of the pancreas called the islets of Langerhans or the pancreatic islets. Glucagon is made by the alpha cells in the islets while insulin is made by the beta cells.
In the liver, glucose molecules are joined together to make a molecule called glycogen. Glycogen acts as a storage reservoir for glucose molecules. The liver absorbs glucose and makes glycogen when the glucose level in the blood is too high. It breaks glycogen down and releases glucose into the bloodstream when the blood glucose concentration is too low. The liver is also able to make glucose molecules from amino acids.
Glucagon and glycogen are sometimes confused due to the similarities in their names. Glucagon is a peptide hormone made by the pancreas. Glycogen is a carbohydrate made by the liver.
Like insulin, glucagon is a peptide hormone and is made of amino acids. A glucagon molecule is a chain of twenty-nine amino acids. Hormones are chemical messengers that travel from their site of origin to their target organ through the blood. When they reach the target, they bind to receptors on the surface of cells. Receptors are proteins on or in the cell membrane that cause a specific effect when they join to the correct molecule.
Control of Blood Sugar by Insulin and Glucagon
As the blood glucose concentration rises and falls during our body's activities, insulin and glucagon act to keep the glucose level constant. When the glucose level in the blood is too high, insulin is released from the pancreas and binds to receptors on cell membranes. This process triggers the passage of glucose into the cells, including those of the liver. Excess glucose is stored in the liver as glycogen. When the blood sugar level is too low, glucagon is released from the pancreas. It binds to liver cells and stimulates the liver to produce glucose by two methods: glycogenolysis and gluconeogenesis.
When glucagon joins to its receptors on liver cell membranes, enzymes that break down glycogen are activated. As the glycogen breaks down, glucose molecules are released. The glucose molecules are then transported into the blood, raising the blood sugar level. The breakdown of glycogen is called glycogenolysis. The term may be easier to remember if a person realizes that in biology "lysis" means the breaking down of a structure or substance.
Glucagon has another important effect on the liver, which also raises the blood sugar level. It stimulates the conversion of amino acids to glucose, a process known as gluconeogenesis. "Genesis" means creation and "neo" means new. The term gluconeogenesis refers to the creation of new glucose molecules.
Comparison of Glucagon and Insulin
Alpha cells of pancreatic islets
Raises blood sugar
Triggers glyogenolysis and gluconeogenesis
Beta cells of pancreatic islets
Lowers blood sugar
Triggers the entry of glucose into cells
Glucagon, Insulin, and Blood Sugar Level
Hypoglycemia in Type 1 Diabetics
Type 1 diabetes is a disorder in which the pancreas no longer makes insulin or makes only a tiny amount. It's an autoimmune condition. The patient's immune system mistakenly attacks and destroys the beta cells in the pancreas. The disorder is generally treated with insulin injections. The timing and quantity of insulin that is injected is vitally important. Too little or too much insulin in the bloodstream in relation to blood sugar level can both be dangerous.
Hypoglycemia is an abnormally low level of blood sugar. The decrease is much larger than the moderate decrease that develops when we haven't eaten for a while or when we've exercised, which glucagon compensates for. In hypoglycemia, the blood sugar may be dangerously low, which can prevent the brain from working properly.
People with type 1 diabetes are in danger of developing hypoglycemia. The condition may occur if the person takes too much insulin, exercises harder than normal, hasn't eaten enough, has drunk too much alcohol, or has taken certain medications which have the side effect of lowering blood sugar.
When people with diabetes develop hypoglycemia, their body may not be able to produce enough glucagon to compensate for the lowered glucose level, or it may not be able to produce glucagon fast enough. First aid and/or medical treatment may be necessary.
Most diabetics have a glucose meter or another method of measuring their blood sugar level. This helps to prevent a problem from developing when their glucose level falls or rises.
Possible Symptoms of Hypoglycemia
Some common symptoms of hypoglycemia include the following:
- blurred vision
- pale skin
- rapid or pounding heartbeat
- feeling faint
Someone suffering from hypoglycemia may also have altered behavior, including aggression. In severe cases they may experience seizures or a coma.
Severe Diabetic Hypoglycemia
Anyone who suspects that they experience periodic episodes of hypoglycemia should visit a doctor for a diagnosis and treatment recommendations.
Treatment for Hypoglycemia in Type 1 Diabetes
Mild to moderate hypoglycemia in diabetics is usually treated by giving the person sweet substances to eat or drink, such as glucose tablets, sugar, honey, or fruit juices. This treatment may be followed by giving the person more substantial food, such as milk, crackers, or a peanut butter sandwich. The person's condition must be monitored after the treatment.
Severe hypoglycemia is life threatening and must be treated by a doctor. In the severe version of the condition, the person loses consciousness or is barely conscious. They are also unable to swallow. A common treatment for severe hypoglycemia is a glucagon injection. Some diabetics have their own glucagon injector, which they carry around with them. Schools may keep a glucagon injector on their premises. Even if a helper injects a severely hypoglycemia diabetic with glucagon and the injection appears to eliminate the person's symptoms, the patient must see a doctor.
Family and acquaintances of someone with diabetes should be familiar with the symptoms of hypoglycemia and its treatments. If they are expected to give a glucagon injection when necessary, they should know the correct technique for giving the injection. Glucagon is supplied as a powder and must be mixed with sterile water just before injection. If it's mixed too early it will become inactive. The water is provided in the injection kit.
The instructions for giving a glucagon injection in the video below are good, but the narrator makes one error in the information that she presents. She says that glucagon is released by the liver when it is actually released by the pancreas.
How to Use a Glucagon Injector
Hypoglycemia in Type 2 Diabetes
In type 1 diabetes, the pancreas produces no or very little insulin. In people with type 2 diabetes, the pancreas does produce insulin. However, the body's cells are often resistant to the hormone's presence and no longer fully respond to it. This prevents sufficient glucose from entering the cells. In some cases the disorder appears when the pancreas is unable to make enough insulin for the body's needs.
People with type 2 diabetes are generally treated with lifestyle changes, medications, and sometimes insulin injections. Patients may sometimes develop mild hypoglycemia and occasionally a severe form of the disorder which requires glucagon administration. People with type 2 diabetes are less likely to require supplemental glucagon than those with type 1 diabetes, however.
As with other hormones, scientists are finding that glucagon may have more functions and more complex behaviour than they previously thought. There are glucagon receptors on cells in the brain, kidney, intestinal smooth muscle, and adipose (fat) tissue as well as on liver cells.
The instructions for making glucagon are encoded in the GCG gene. Like other genes, the GCG gene contains instructions for making a protein. This protein is called preproglucagon. It's broken down into a smaller protein called proglucagon. This in turn breaks down into even smaller proteins, one of which is glucagon. The functions of the other proteins that are produced is of great interest to researchers.
Another topic of interest for scientists is the control of glucagon production and secretion by the nervous system. At the moment, this control is not well understood. Understanding the control system could be very important for helping diabetics.
Type 1 diabetes was once thought to be simply a pancreatic problem in which insulin is no longer produced by the pancreatic islets. According to this theory, if the insulin is replaced, the person's symptoms will disappear.
A lack of insulin is certainly involved in type 1 diabetes and insulin is definitely an essential treatment for the disorder. However, researchers suspect that the interactions between the central nervous system, insulin, glucagon, and perhaps hormones that resemble glucagon are also important in diabetes. Understanding these interactions may lead to new treatments for the disease.
The human endocrine system, or the hormonal system, is very complex. There's still a lot to be learned about hormone identity, secretion, and action. Researchers are gradually discovering how hormones such as glucagon work, however, which could be very helpful for treating disease.
- Glucagon facts from Colorado State University
- Glucagon and blood sugar level information from WebMD
- Information about low blood glucose (hypoglycemia) in diabetes from the National Institutes of Health or NIH
- Type 2 diabetes treatment facts from the National Health Service or NHS
- Information about the GCG gene from GeneCards, Weizmann Institute of Science
- Glucagon physiology and pathophysiology facts from Medscape
Questions & Answers
© 2012 Linda Crampton