Understanding Glucagon as a Peptide Hormone

June 17, 2025

Glucagon is a peptide hormone that helps regulate blood sugar levels and maintain a balanced metabolism. It’s produced by the alpha cells of the pancreas and works to raise blood glucose levels when they drop too low, thereby balancing the effect of insulin.

If you’ve been wondering, “Is glucagon a peptide hormone?” The answer is a clear yes.

However, it’s not just about the classification, but also about how glucagon manages your body’s energy and helps maintain stable blood sugar levels, especially if you're managing diabetes or other metabolic conditions.

Did you know? According to the International Diabetes Federation Diabetes Atlas 11th Edition (2025), India had an estimated 89.8 million adults (aged 20–79 years) living with diabetes in 2024.

This places India second globally in terms of the number of people affected, emphasising the urgent need for effective blood glucose regulation and metabolic health management.

In this article, we’ll explore glucagon, its role in regulating blood glucose alongside insulin, and its importance for overall wellness, diabetes management, and gut health.

What is glucagon?

Glucagon is a peptide hormone made of 29 amino acids. Unlike lipid-soluble steroid hormones, glucagon is water-soluble and binds to cell surface receptors to trigger intracellular signalling.

Regulates blood glucose levels, especially during hypoglycemia.
Released from the alpha cells of the pancreas when glucose levels drop, such as during fasting or between meals.
Binds to liver cell receptors to trigger:

Glycogen breakdown (glycogenolysis).
Glucose production from non-carbohydrate sources (gluconeogenesis).

Raises blood glucose levels to fuel vital organs, like the brain.

Here’s a comparison of glucagon with steroid and amine hormones:

Feature	Glucagon (Peptide Hormone)	Steroid Hormones	Amine Hormones
Chemical nature	Chain of amino acids (polypeptide)	Derived from cholesterol	Derived from single amino acids
Solubility	Water-soluble	Lipid-soluble	Water-soluble
Receptor location	Cell surface receptors	Intracellular receptors	Cell surface or intracellular
Example hormones	Glucagon, insulin	Cortisol, oestrogen	Epinephrine, thyroid hormones

Now, to fully understand glucagon's role in the body, it’s essential to explore how it is produced and what triggers its release.

Also read: Understanding glucagon: sources, functions, and effects on health

How is glucagon produced, and what triggers its release?

Glucagon is produced by alpha cells in the pancreas, which are located in small clusters called the islets of Langerhans. These cells create glucagon by processing a larger molecule called proglucagon into the active hormone, which is then released into the bloodstream.

Several factors trigger glucagon release:

Low blood sugar: When glucose drops (e.g., during fasting or exercise), alpha cells release glucagon to signal the liver to produce glucose, raising blood sugar.
Protein intake: Amino acids from protein-rich foods stimulate glucagon release, helping balance blood sugar after a low-carb meal.
Hormonal and nervous system signals: Stress hormones and nervous system signals trigger glucagon release during stress or exercise.

At the same time, glucagon release is reduced by the following factors:

High blood sugar: When glucose levels are high, glucagon secretion is suppressed to prevent further blood sugar increases
Insulin: Insulin, produced by beta cells in the pancreas, directly inhibits glucagon release, helping to keep blood sugar balanced
Somatostatin: Produced by delta cells in the pancreas, somatostatin inhibits both insulin and glucagon secretion, acting as a regulator

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Also read: How to naturally increase GLP-1 levels

This balanced system ensures that glucagon is released when needed to raise blood sugar and suppressed when it isn’t, maintaining steady energy levels for the body.

How does glucagon work: functions and mechanisms?

Glucagon’s primary function is to keep your blood sugar (glucose) from dropping too low. Let’s understand how it works!

What happens when your blood sugar drops?

When your blood sugar level falls, your pancreas releases glucagon. This hormone acts mainly on your liver to help restore normal blood sugar levels through several key processes:

Glycogenolysis: Glucagon tells your liver to break down glycogen (the stored form of glucose) into glucose. The liver then releases this glucose into your bloodstream, quickly raising your blood sugar.
Gluconeogenesis: If your glycogen stores are low, glucagon triggers your liver to make new glucose from non-carbohydrate sources, such as amino acids. This keeps your blood sugar steady even when you haven’t eaten for a while.
Lipolysis: Glucagon also helps your body break down fat stores into fatty acids. These fatty acids can be used for energy when glucose is in short supply.

How does glucagon signal your cells?

Glucagon binds to receptors on liver cells, triggering a chain reaction that produces cyclic adenosine monophosphate (cAMP). Increased cAMP activates protein kinase A (PKA), which then activates enzymes to break down glycogen and produce glucose, quickly raising blood sugar levels.

How do glucagon and insulin work together?

Glucagon and insulin have opposite effects, but they work together to regulate blood glucose levels and maintain a healthy balance.

Glucagon raises blood sugar by prompting the liver to release glucose.
Insulin lowers blood sugar by helping your body’s cells absorb and store glucose.

This balance is especially important if you have diabetes or another metabolic condition.

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Now, let’s understand glucagon’s role in regulating blood glucose levels and its overall mechanism of action.

How does glucagon regulate blood glucose levels?

Glucagon and insulin work together to maintain glucose homeostasis. While insulin lowers blood glucose by promoting its uptake and storage, glucagon raises blood glucose levels when needed. This balance ensures stable glucose levels, supporting overall health.

1. Integration with other metabolic pathways

In addition to regulating glucose, glucagon influences fat and protein metabolism. It promotes lipolysis in adipose tissue, providing fatty acids and ketone bodies as alternative fuel sources when glucose is scarce, ensuring vital organs, particularly the brain, continue to receive energy during challenging conditions.

2. The insulin-glucagon balance

Insulin and glucagon secretion are tightly regulated by blood glucose levels:

Insulin lowers blood glucose, acting on muscle, fat, and liver to promote glucose uptake and storage.
Glucagon raises blood glucose, primarily acting on the liver to stimulate glucose release and production.

When blood glucose levels rise after a meal, insulin predominates, promoting the storage of glucose in the body. During fasting or stress, glucagon takes over, ensuring a steady supply of glucose.

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What are the clinical relevance and health conditions related to glucagon?

Glucagon’s clinical importance extends well beyond its physiological role in glucose regulation, as it directly impacts the management of diabetes and rare endocrine disorders.

1. Glucagon in diabetes management

In both Type 1 and Type 2 diabetes, dysregulation of glucagon secretion contributes to the abnormal elevation of blood glucose levels.

Excessive glucagon release can worsen hyperglycemia by stimulating glucose production in the liver.
Glucagon deficiency, though rare, increases the risk of hypoglycemia, especially in patients using insulin.

2. Glucagonoma and hyperglucagonaemia

Hyperglucagonaemia typically results from glucagon-secreting pancreatic neuroendocrine tumours, known as glucagonomas. These tumours cause chronic glucagon elevation, leading to:

Persistent hyperglycemia
Weight loss
Necrolytic migratory erythema (a distinctive skin rash)

Additional symptoms

Glucose intolerance
Diarrhea
Excessive thirst and frequent urination
Neurological or psychiatric issues in some cases

3. Management of glucagonoma

Treatment goals
The primary focus is to manage the metabolic effects of excess glucagon. Here’s how it's typically treated:

Somatostatin analogues (e.g., octreotide, lanreotide) suppress glucagon production, thereby alleviating symptoms such as weight loss and rash.
Surgical removal of the tumour is the most effective treatment, potentially curing the condition if normalising glucagon levels localises the cancer.
For metastatic or unresectable tumours, treatment includes chemotherapy and targeted therapies for symptom management.

4. Prognosis and ongoing care

While most glucagonomas are malignant, they tend to grow slowly. With proper management, patients can survive for many years.
A multidisciplinary approach involving endocrinologists, oncologists, surgeons, and specialised nurses helps in monitoring and adjusting therapy according to individual needs.

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Having understood the clinical impact of glucagon, it's also pertinent to know how glucagon levels are measured and what these levels mean for health.

How are glucagon levels tested, and what do they mean?

Testing glucagon levels provides insights into pancreatic function, metabolic health, and the diagnosis of specific endocrine disorders. Here’s a breakdown of how glucagon levels are measured and what the results mean.

How are glucagon levels measured in the blood?

Glucagon levels are typically measured through blood tests, but due to its low concentration and susceptibility to interference, these tests require careful handling and specialised techniques. Common methods include:

1. Immunoassays (ELISA and RIA)

These tests use antibodies to detect and measure glucagon concentration in plasma. Sample pretreatment, such as ethanol extraction, helps minimise interference from other proteins and glucagon-like peptides for more accurate results.

2. Mass spectrometry (LC-HRMS)

This advanced method offers high sensitivity and specificity, utilising protein precipitation, solid-phase extraction, and internal standards for precise measurement of glucagon. Mass spectrometry is the gold standard for glucagon assays due to its accuracy and ability to distinguish it from similar peptides.

3. Glucagon stimulation test

In some clinical cases, glucagon is given to stimulate hormone responses like insulin or cortisol, with blood samples used to assess pancreatic or adrenal function. This test helps evaluate insulin secretion in diabetes or adrenal function in pediatric endocrinology.

What is the normal range for glucagon levels?

In healthy adults, fasting glucagon levels typically range from 25 to 50 picograms per millilitre (pg/mL), or about 7–10 picomoles per litre (pmol/L). These values can vary depending on the assay used and laboratory standards.

Low glucagon levels: In rare cases, low levels may indicate pancreatic insufficiency or other metabolic issues.
High glucagon levels: Elevated levels can be observed in conditions such as diabetes, glucagonoma (a tumour that secretes glucagon), or during periods of metabolic stress.

Precise measurement of glucagon helps in diagnosing endocrine disorders, monitoring metabolic health, and managing conditions such as diabetes and glucagon-secreting tumours.

Also Read: How to improve metabolic age for effective weight loss

When you step back, it’s incredible how much is happening beneath the surface to keep your body in balance. While glucagon may not get as much attention as insulin, it ensures your brain and muscles always have the fuel they need, especially during fasting or exercise.

The way glucagon, insulin, and somatostatin work together shows how our bodies continuously adjust to life’s demands. Understanding these hormones isn’t just for science enthusiasts or those with diabetes; it’s knowledge that helps us make more informed health choices. Every meal, workout, and night of sleep supports this delicate hormonal balance.

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