RESEARCH STARTER
Glucagon
Glucagon is a peptide hormone produced in the pancreas that plays a vital role in regulating blood sugar levels, particularly when they drop below normal. It works in opposition to insulin, which lowers blood sugar levels after eating by facilitating the uptake of glucose into cells. When blood sugar levels decrease, glucagon signals the liver to release stored glucose and to produce new glucose from non-carbohydrate sources, such as lipids and amino acids. This is crucial for maintaining energy supply, especially for the brain, which depends heavily on glucose.
Medically, glucagon is synthesized for therapeutic use, particularly to treat acute hypoglycemia, a condition characterized by dangerously low blood sugar levels. It can be administered through injections and is effective in raising blood glucose rapidly. Additionally, glucagon serves as a diagnostic tool in gastrointestinal radiology to relax the digestive tract before imaging procedures. Understanding glucagon's function complements the knowledge of diabetes management and the overall hormonal balance involved in glucose homeostasis in the body.
Authored By: Ferguson, Grace 1 of 2
Published In: 2024 2 of 2
Full Article
Glucose, the body’s primary source of energy, is a sugar that is derived from carbohydrate foods. Glucagon, a peptide hormone generated in the pancreas, plays a key role in maintaining regular levels of glucose in the blood. Similar to insulin, glucagon is produced by cells in the pancreas. However, insulin and glucagon have opposite effects. When people eat, their blood sugar level increases. To reduce the blood sugar level, the pancreas releases insulin, which removes the sugar from the food and transports it to the respective cells so it can be transformed into energy. This process brings the blood sugar level back down. Conversely, glucagon’s main purpose is to increase blood glucose levels. When the blood glucose level begins to dip below the normal amount, more glucose needs to be found and pumped into the blood. Glucagon makes this possible by signaling the liver, which dispenses glucose. From a medicinal viewpoint, glucagon is manufactured as a life-saving drug, chiefly used to treat acute hypoglycemia, or very low blood sugar.
Background
In 1922, while separating insulin from aqueous pancreas extracts, scientists John Murlin and Charles Kimball came upon a substance they regarded as having a distinct impact on low blood sugar. This substance was named glucagon. Many years after this discovery, researchers found it difficult to isolate and purify glucagon. Studies continued for nearly thirty years until researcher William Bromer and his associates purified and determined the structure off the substance.
Although the connection between insulin and glucagon has become an extensively studied area of endocrinology and biochemistry, early researchers were more interested in insulin due to its role in controlling diabetes. During early research on insulin, a swift transitory hyperglycemia was detected in animals that were injected with certain pancreatic extracts. The liver was shown to be the site of the hyperglycemic activity. It was then discovered that glucagon causes glycogenolysis—the process of breaking glycogen down into glucose to provide the body with energy and maintain fasting blood glucose levels—in liver slices. Researchers then began to search for ways to facilitate intensive study concerning the mechanism of this effect. It took almost thirty years for Bromer and his associates to obtain a pure version of glucagon, and the substance has undergone considerable advancement since then. Besides being isolated in crystalline form, its structure has been fully determined, and its hyperglycemic effects are well defined.
Glucagon has distinct effects on the liver and other areas of the body. When blood sugar levels start to drop, glucagon is crucial to restoring them to the normal range. Glucagon controls two vital metabolic pathways in the liver that allow the liver to release glucose to the rest of the body. Under the first method of action, glucagon breaks down glycogen, a molecule in the body that stores glucose in the liver. Specifically, when blood sugar levels begin to drop, glucagon is released via the activation of enzymes that break down glycogen and produce glucose. The second method of action allows glucagon to activate gluconeogenesis, which is the pathway that enables non-hexose substrates, such as glycerol and amino acids, to be converted into glucose; this method provides the bloodstream with an additional source of glucose.
Glucagon is also vital to the brain, which uses a significant amount of energy but contains only a limited amount of glycogen and relies on the bloodstream for a constant supply of glucose.
Overview
The glucagon hormone is made up of twenty-nine amino acids. Carbohydrate-rich foods—such as sweets, bread, potatoes, fruit, milk, and cereal—are the body’s main source of glucose. When people eat these types of foods, the bloodstream absorbs glucose and moves it to the body’s cells. If more glucose than the body needs at the time is consumed, the extra glucose is stored in the liver and muscles as glycogen. Notably, not eating enough carbohydrates can deplete glycogen. Between meals, glycogen can be used by the body for energy. When the blood glucose level begins to decline, glucagon binds to receptors, which are located in the liver, signaling the liver to break down and release glucose into the bloodstream.
As a medication, glucagon is a synthetic, manufactured version of the glucagon hormone. Although glucagon is primarily used to treat severe hypoglycemia, it is also used as a diagnostic aid in gastrointestinal radiology. In the latter case, glucagon is used to relax the gastrointestinal tract prior to radiologic examinations. Like insulin, glucagon is an important hormone that enables the body to maintain blood sugar, or glucose, in a narrow range. Whether an individual has hyperglycemia, diabetes, or another type of sugar-related ailment is ultimately determined by blood glucose testing and clinical diagnosis. Advances have led to the development of combination drugs that target glucagon along with other hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), to improve blood glucose control and support weight loss. In clinical trials, a drug called retatrutide, which targets glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), has been shown to lower glycated hemoglobin (HbA1c) by about 2 percent and reduce body weight by about 15 to 17 percent.
People with hyperglycemia may exhibit a range of symptoms, including a blood glucose level above 180 to 200 mg/dL, frequent urination, blurry vision, difficulty concentrating, dizziness, sleepiness, and confusion. In people with diabetes, hypoglycemia can occur as a side effect to certain diabetes medications, such as chlorpropamide, glimepiride, glipizide, glyburide (also called glibenclamide), and nateglinide. Specific drugs, such as danazol, insulin, and glucocorticoids, may increase glucose levels. Notably, levels can also increase after extended fasting or rigorous exercise. Drugs that may decrease glucose levels include secretin, propranolol, and atenolol.
Because the kidneys are important in glucagon clearance, chronic kidney disease can reduce glucagon clearance. In patients with cardiac disease, glucagon may elevate blood pressure, pulse rate, and the demand for oxygen, all of which may be life threatening. In patients with pheochromocytoma, an adrenal gland tumor, glucagon can cause the tumor to produce catecholamines, resulting in a sudden and significant hike in blood pressure. Catecholamines are hormones generated by adrenal glands.
Glucagon is generally administered via injection under the skin, in the vein, or in the muscle. The drug comes in powder and liquid forms, which are combined prior to administration. Intravenous effects are reported to be virtually instantaneous, within about 1 minute. Intramuscular effects generally start within 5 to 15 minutes. Developments include oral forms of glucagon-like peptide-1 (GLP-1)–based drugs and longer-acting formulations, which are easier to use and do not always require injection.
Prior to using glucagon, patients should tell their physicians whether they are allergic to any medications or foods, types of prescription and nonprescription substances they are taking, including vitamins, and whether they are pregnant or have other relevant health conditions.
Bibliography
Carson, Ed. “Eli Lilly Confirms ‘Superior Weight Loss’ Of Its Next‑Generation Obesity Drug.” Investor’s Business Daily, 19 Mar. 2026, www.investors.com/news/technology/eli-lilly-experimental-drug-retatrutide-trong-weight-loss-trial/. Accessed 26 Mar. 2026.
Chabenne, Joseph R., et al. “Optimization of the Native Glucagon Sequence for Medicinal Purposes.” Journal of Diabetes Science and Technology, vol. 4, no. 6, 2010, pp. 1322–31, doi:10.1177/193229681000400605. Accessed 26 Mar. 2026.
"Glucagon Injection." MedlinePlus, US National Library of Medicine, 15 June 2025, medlineplus.gov/druginfo/meds/a682480.html. Accessed 26 Mar. 2026.
"Glycogenolysis." Britannica, 20 July 2024, www.britannica.com/science/glycogenolysis. Accessed 30 Mar. 2026.
Grøndahl, Magnus F. G., et al. “Glucagon Clearance Is Decreased in Chronic Kidney Disease but Preserved in Liver Cirrhosis.” Diabetes, vol. 73, no. 10, 2024, pp. 1641–52, American Diabetes Association, doi.org/10.2337/db24-0305. Accessed 26 Mar. 2026.
Parker, J. A., et al. “Glucagon and GLP-1 Inhibit Food Intake and Increase C-Fos Expression in Similar Appetite Regulating Centres in the Brainstem and Amygdala.” International Journal of Obesity, 2005, vol. 37, no. 10, 2013, pp. 1391–98, doi:10.1038/ijo.2012.227. Accessed 26 Mar. 2026.
Picazo, J., editor. Glucagon in Gastroenterology. Springer Science Business Media, 1979.
Shao, Q., J. Xiong, J. Wu, J. Mao, and Q. Hu. "Research Progress on Oral Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Diabetes Mellitus Type 2." Frontiers in Molecular Biosciences, vol. 12, 2026, article 1729904, doi.org/10.3389/fmolb.2025.1729904. Accessed 26 Mar. 2026.
Smith, Denise L., et al. Exercise Physiology for Health, Fitness, and Performance. 6th ed., Wolters Kluwer, 2023.
Unger, Roger H., et al. “Dissecting the Actions of Widely Used Diabetes Drugs.” Nature Medicine, vol. 19, no. 3, 2013, pp. 272–73, doi:10.1038/nm.3123. Accessed 26 Mar. 2026.
Wen, Jimmy, et al. “Next Generation Dual GLP‑1/GIP, GLP‑1/Glucagon, and Triple GLP‑1/GIP/Glucagon Agonists: A Literature Review.” Nutrition, Metabolism & Cardiovascular Diseases, vol. 35, no. 12, Dec. 2025, p. 104213. www.nmcd-journal.com/article/S0939-4753(25)00367-9/abstract. Accessed 26 Mar. 2026.
Full Article
Glucose, the body’s primary source of energy, is a sugar that is derived from carbohydrate foods. Glucagon, a peptide hormone generated in the pancreas, plays a key role in maintaining regular levels of glucose in the blood. Similar to insulin, glucagon is produced by cells in the pancreas. However, insulin and glucagon have opposite effects. When people eat, their blood sugar level increases. To reduce the blood sugar level, the pancreas releases insulin, which removes the sugar from the food and transports it to the respective cells so it can be transformed into energy. This process brings the blood sugar level back down. Conversely, glucagon’s main purpose is to increase blood glucose levels. When the blood glucose level begins to dip below the normal amount, more glucose needs to be found and pumped into the blood. Glucagon makes this possible by signaling the liver, which dispenses glucose. From a medicinal viewpoint, glucagon is manufactured as a life-saving drug, chiefly used to treat acute hypoglycemia, or very low blood sugar.
Background
In 1922, while separating insulin from aqueous pancreas extracts, scientists John Murlin and Charles Kimball came upon a substance they regarded as having a distinct impact on low blood sugar. This substance was named glucagon. Many years after this discovery, researchers found it difficult to isolate and purify glucagon. Studies continued for nearly thirty years until researcher William Bromer and his associates purified and determined the structure off the substance.
Although the connection between insulin and glucagon has become an extensively studied area of endocrinology and biochemistry, early researchers were more interested in insulin due to its role in controlling diabetes. During early research on insulin, a swift transitory hyperglycemia was detected in animals that were injected with certain pancreatic extracts. The liver was shown to be the site of the hyperglycemic activity. It was then discovered that glucagon causes glycogenolysis—the process of breaking glycogen down into glucose to provide the body with energy and maintain fasting blood glucose levels—in liver slices. Researchers then began to search for ways to facilitate intensive study concerning the mechanism of this effect. It took almost thirty years for Bromer and his associates to obtain a pure version of glucagon, and the substance has undergone considerable advancement since then. Besides being isolated in crystalline form, its structure has been fully determined, and its hyperglycemic effects are well defined.
Glucagon has distinct effects on the liver and other areas of the body. When blood sugar levels start to drop, glucagon is crucial to restoring them to the normal range. Glucagon controls two vital metabolic pathways in the liver that allow the liver to release glucose to the rest of the body. Under the first method of action, glucagon breaks down glycogen, a molecule in the body that stores glucose in the liver. Specifically, when blood sugar levels begin to drop, glucagon is released via the activation of enzymes that break down glycogen and produce glucose. The second method of action allows glucagon to activate gluconeogenesis, which is the pathway that enables non-hexose substrates, such as glycerol and amino acids, to be converted into glucose; this method provides the bloodstream with an additional source of glucose.
Glucagon is also vital to the brain, which uses a significant amount of energy but contains only a limited amount of glycogen and relies on the bloodstream for a constant supply of glucose.
Overview
The glucagon hormone is made up of twenty-nine amino acids. Carbohydrate-rich foods—such as sweets, bread, potatoes, fruit, milk, and cereal—are the body’s main source of glucose. When people eat these types of foods, the bloodstream absorbs glucose and moves it to the body’s cells. If more glucose than the body needs at the time is consumed, the extra glucose is stored in the liver and muscles as glycogen. Notably, not eating enough carbohydrates can deplete glycogen. Between meals, glycogen can be used by the body for energy. When the blood glucose level begins to decline, glucagon binds to receptors, which are located in the liver, signaling the liver to break down and release glucose into the bloodstream.
As a medication, glucagon is a synthetic, manufactured version of the glucagon hormone. Although glucagon is primarily used to treat severe hypoglycemia, it is also used as a diagnostic aid in gastrointestinal radiology. In the latter case, glucagon is used to relax the gastrointestinal tract prior to radiologic examinations. Like insulin, glucagon is an important hormone that enables the body to maintain blood sugar, or glucose, in a narrow range. Whether an individual has hyperglycemia, diabetes, or another type of sugar-related ailment is ultimately determined by blood glucose testing and clinical diagnosis. Advances have led to the development of combination drugs that target glucagon along with other hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), to improve blood glucose control and support weight loss. In clinical trials, a drug called retatrutide, which targets glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), has been shown to lower glycated hemoglobin (HbA1c) by about 2 percent and reduce body weight by about 15 to 17 percent.
People with hyperglycemia may exhibit a range of symptoms, including a blood glucose level above 180 to 200 mg/dL, frequent urination, blurry vision, difficulty concentrating, dizziness, sleepiness, and confusion. In people with diabetes, hypoglycemia can occur as a side effect to certain diabetes medications, such as chlorpropamide, glimepiride, glipizide, glyburide (also called glibenclamide), and nateglinide. Specific drugs, such as danazol, insulin, and glucocorticoids, may increase glucose levels. Notably, levels can also increase after extended fasting or rigorous exercise. Drugs that may decrease glucose levels include secretin, propranolol, and atenolol.
Because the kidneys are important in glucagon clearance, chronic kidney disease can reduce glucagon clearance. In patients with cardiac disease, glucagon may elevate blood pressure, pulse rate, and the demand for oxygen, all of which may be life threatening. In patients with pheochromocytoma, an adrenal gland tumor, glucagon can cause the tumor to produce catecholamines, resulting in a sudden and significant hike in blood pressure. Catecholamines are hormones generated by adrenal glands.
Glucagon is generally administered via injection under the skin, in the vein, or in the muscle. The drug comes in powder and liquid forms, which are combined prior to administration. Intravenous effects are reported to be virtually instantaneous, within about 1 minute. Intramuscular effects generally start within 5 to 15 minutes. Developments include oral forms of glucagon-like peptide-1 (GLP-1)–based drugs and longer-acting formulations, which are easier to use and do not always require injection.
Prior to using glucagon, patients should tell their physicians whether they are allergic to any medications or foods, types of prescription and nonprescription substances they are taking, including vitamins, and whether they are pregnant or have other relevant health conditions.
Bibliography
Carson, Ed. “Eli Lilly Confirms ‘Superior Weight Loss’ Of Its Next‑Generation Obesity Drug.” Investor’s Business Daily, 19 Mar. 2026, www.investors.com/news/technology/eli-lilly-experimental-drug-retatrutide-trong-weight-loss-trial/. Accessed 26 Mar. 2026.
Chabenne, Joseph R., et al. “Optimization of the Native Glucagon Sequence for Medicinal Purposes.” Journal of Diabetes Science and Technology, vol. 4, no. 6, 2010, pp. 1322–31, doi:10.1177/193229681000400605. Accessed 26 Mar. 2026.
"Glucagon Injection." MedlinePlus, US National Library of Medicine, 15 June 2025, medlineplus.gov/druginfo/meds/a682480.html. Accessed 26 Mar. 2026.
"Glycogenolysis." Britannica, 20 July 2024, www.britannica.com/science/glycogenolysis. Accessed 30 Mar. 2026.
Grøndahl, Magnus F. G., et al. “Glucagon Clearance Is Decreased in Chronic Kidney Disease but Preserved in Liver Cirrhosis.” Diabetes, vol. 73, no. 10, 2024, pp. 1641–52, American Diabetes Association, doi.org/10.2337/db24-0305. Accessed 26 Mar. 2026.
Parker, J. A., et al. “Glucagon and GLP-1 Inhibit Food Intake and Increase C-Fos Expression in Similar Appetite Regulating Centres in the Brainstem and Amygdala.” International Journal of Obesity, 2005, vol. 37, no. 10, 2013, pp. 1391–98, doi:10.1038/ijo.2012.227. Accessed 26 Mar. 2026.
Picazo, J., editor. Glucagon in Gastroenterology. Springer Science Business Media, 1979.
Shao, Q., J. Xiong, J. Wu, J. Mao, and Q. Hu. "Research Progress on Oral Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Diabetes Mellitus Type 2." Frontiers in Molecular Biosciences, vol. 12, 2026, article 1729904, doi.org/10.3389/fmolb.2025.1729904. Accessed 26 Mar. 2026.
Smith, Denise L., et al. Exercise Physiology for Health, Fitness, and Performance. 6th ed., Wolters Kluwer, 2023.
Unger, Roger H., et al. “Dissecting the Actions of Widely Used Diabetes Drugs.” Nature Medicine, vol. 19, no. 3, 2013, pp. 272–73, doi:10.1038/nm.3123. Accessed 26 Mar. 2026.
Wen, Jimmy, et al. “Next Generation Dual GLP‑1/GIP, GLP‑1/Glucagon, and Triple GLP‑1/GIP/Glucagon Agonists: A Literature Review.” Nutrition, Metabolism & Cardiovascular Diseases, vol. 35, no. 12, Dec. 2025, p. 104213. www.nmcd-journal.com/article/S0939-4753(25)00367-9/abstract. Accessed 26 Mar. 2026.