Glucagon: What It Is, Function & Side Effects

When we speak of diabetic hormones or blood sugar control, the hormone that comes to mind is insulin.

However, there is a counter-regulatory hormone that many often don’t know, and it is known as the glucagon hormone.

But what is glucagon hormone? How does it function, and what does it achieve? 

What are the normal levels, and what can cause these levels to be off the normal margins? 

Can it be synthetic and offered as a drug? If so, what are the dosages and side effects?

Now, if you are asking yourself these questions, then you are reading the right piece.

Together let’s find out about this glucagon hormone.

What is glucagon?

Glucagon is a peptide hormone produced by the pancreas in response to hypoglycemia.

Usually, glucagon is produced in response to hypoglycemic conditions when blood glucose falls below normal levels. This is in a bid to raise blood glucose levels and thus maintain normal functioning of the body.

What is the function of glucagon?

Primarily, glucagon is released into the bloodstream to increase glucose levels. Thus, it increases energy expenditure. 

Apart from increasing blood sugar levels, glucagon goes beyond this. It is known for having a positive inotropic and chronotropic effect on the heart and also reduces body weight by reducing food intake and promoting lipolysis. 

However, it mainly acts on the liver to promote glucose production de novo and inhibit glycogen synthesis. So, essentially, glucagon works to increase blood sugar levels.

Glucagon vs insulin

Now that we know what glucagon is and its function, how similar or different is it from insulin?

Similarities

First of all, both hormones are involved in the regulation of blood glucose. Secondly, they are both peptide hormones, and thirdly, they are both produced by the pancreas islet of Langerhans cells.

However, that is as much as it goes for similarities. Fundamentally, they are different just as the different purposes that they serve.

Differences

For one, while insulin is produced by red pancreatic beta cells, glucagon is produced by green alpha cells.

Secondly, insulin is involved in lowering blood sugar, while glucagon is involved in increasing sugar levels in the blood. 

Therefore, while insulin leads to the entry of glucose into the cells, glucagon leads to the release of the same glucose into the bloodstream. 

Thirdly, while insulin promotes glycogenesis, insulin promotes glycogenolysis. 

Glycogen is the stored form of glucose. In forming more glycogen, insulin helps reduce glucose levels in the blood, while glucagon, on the other hand, helps break down glycogen stores into glucose, thus increasing its levels. 

Insulin also promotes lipogenesis, while glucagon acts to promote lipolysis. As such, insulin may lead to weight gain as opposed to glucagon, which leads to weight loss.

While insulin acts solely to reduce blood sugar, glucagon has other hormones to help with raising blood glucose levels, including cortisol and thyroid hormone. This is why glucagon deficit is not common clinically as insulin deficiency. 

Finally, insulin deficiency leads to diabetes type 1 or type 2, while glucagon deficiency can only lead to hypoglycemia and glucagonoma primarily.

In summary, insulin and glucagon are similar hormones in their involvement in blood sugar, except that they are counter-regulatory.

Glucagon vs glycogen

Glucagon and glycogen may sound similar in pronunciation, and perhaps you are asking yourself what the differences are.

In simple terms, glycogen is the form in which the body stores extra energy in the liver and skeletal muscles. Conversely, glucagon is a hormone that the body secretes to utilize the available glycogen.

Therefore, glycogen is what glucagon acts on.

Signs of low glucagon levels

So, why should we be interested in glucagon?

Normally, in cases of low glucagon levels, one experiences marked hypoglycemia due to low blood sugar levels. 

This is a situation that requires immediate medical attention as it may be fatal. Usually, it presents with fatigue, and coma and may easily progress to sudden death.

For this reason, it is important to identify tell-tale signs of low glucagon to prevent the inevitable doom brought by hypoglycemia.

Low glucagon levels usually present clinically with:

• Shaking and trembling
• Increased heart rate
• Dizziness and drowsiness
• Hunger
• Nervousness
• Irritability
• Pale skin
• Weakness
• Tingling and numbness

If you notice these signs, it is recommended that you see your doctor for a check-up on your glucagon levels.

When to see a doctor about your glucagon levels

You must see your physician if you are a known diabetic experiencing frequent episodes of low blood glucose. This is especially true for those suffering from type 1 diabetes which is considered genetic.

Even though glucagon levels are not usually measured, your physician may need to adjust your medicine for a better response to episodic hypoglycemia.

How to test glucagon levels

The glucagon test is not a routine test. However, in some situations, it can be very necessary to carry out the test. 

These clinical conditions necessitating measuring of glucagon levels include:

• Diabetes (Especially in a patient experiencing recurring episodes of hypoglycemia)
• Glucagonoma
• Liver cirrhosis
• Hypoglycemia
• Multiple endocrine neoplasia type I
• Pancreatitis
• Growth hormone deficiency in children

The glucagon test is a blood test. This means a blood sample is taken, and levels of glucagon are measured in the blood. 

Fasting can influence the outcome of results, and thus it is advisable to consult your physician on whether you should fast or not and for how long before the actual test.

What are normal glucagon levels?

Glucagon levels depend on the fasting period before checking them, glucose levels, and scales or equipment used by different labs. 

Therefore, it is essential to check with your physician on the results received from the lab and ask questions where clarification is needed.

Normal levels range from 50-100 picogram/deciliter(pg./dL) of blood.

What can cause low glucagon levels?

Glucagon, as we have seen, is an essential hormone in blood glucose regulation. However, some situations can lead to abnormal levels – either higher or lower than normal.

In those situations where glucagon is way above normal, it leads to hyperglycemia. The constant hyperglycemic condition will then lead to acquired diabetes mellitus, which has many complications, including peripheral neuropathy, nephropathy, microangiopathy, and macroangiopathy that often manifest in the classical diabetic foot.

Conditions that may lead to increased levels of glucagon production include glucagonoma and multiple endocrine neoplasms.

On the other hand, some conditions do impair the production of glucagon. The result of these pathological conditions leads to an induced state of hypoglycemia and poor control of blood sugar levels. 

These include:

Pancreatitis

This is the inflammation of the pancreas. It can either be acute or chronic, but in both cases, the endocrine function of the organ is impaired. 

As a result, there is reduced production and secretion of glucagon, leading to low blood sugar levels.

Pancreatotomy

This is surgery that involves the removal of the pancreas. As such, it leads to a lack of the essential hormones that the pancreas produces and, thus, impaired regulation of blood glucose levels. 

Usually, this can be treated by hormone replacement therapy for both glucagon and insulin.

Additionally, there can be enough insulin but impaired receptors. This affects the functioning of the hormone. While glucagon acts on diverse effector organs, the main organ of action is the liver. 

Therefore, conditions that affect the liver, such as end-stage liver diseases leading to liver cirrhosis, are going to impair glucagon function. 

In liver cirrhosis particularly, scar tissue is formed, and this reduces the ability of glucose release or glycolysis to take place. This will thus lead to hypoglycemia as glucagon cannot work properly.

What are glucagon injections?

Glucagon injection is a prescription used in cases of severe hypoglycemia.

They normally come in various packaging as either vials, auto-injector, or in prefilled syringes.

They may also be used for diagnostic purposes for the gastrointestinal tract, especially in radiographs looking to catch bowel movements. 

However, we should note that injections are not the only glucagon prescriptions. It can also come in other forms, such as dry nasal sprays.

When would you use glucagon injections?

For the cases of low glucagon production and secretion, synthetic glucagon is put to use.

However, it cannot be used over the counter but rather under prescription, and usually, it is used as a last resort when someone is unconscious, unable to eat, or experiencing a seizure.

Before taking, it is advisable to check with your doctor on the possibility of an insulinoma or pheochromocytoma, as it is contraindicated in both conditions.

Also, it is not advisable to take glucagon with anticholinergics as there will be an increased incidence of side effects of both drugs.

How to administer glucagon injections

Using glucagon needs careful and precise usage. It is important to note the following before administering.

• Just before using glucagon, make sure you have read the instructions and understood them well. If you are a caregiver, be sure to call for emergency medical help in cases of severe hypoglycemia.
• Usually, glucagon injection is given just under the skin (subcutaneously), into your vein (intravenously), or the muscle (intramuscular). After the injection, inform your doctor about it and take a carbohydrate-rich diet.
• 1mg is normally given parenterally, while 3mg is the maximum dose for one actuation for hypoglycemia. For diagnostic purposes in the gastrointestinal tract, 1mg to 2mg IM and 0.5 to 0.75mg IV are used for the colon, while for the stomach, duodenum, and small bowel, the dosages are a little lower.
• Some of the injections need to be diluted before use. Reconstitution must be done correctly. If you have no clue how to dilute, seek assistance.
• Finally, if the glucagon has changed color or has particles, or has expired, do not use it. 

Do glucagon injections have any side effects?

Glucagon has its side effects just as any other drug, which may not need medical attention necessarily. 

Side effects can include allergic reactions, including redness, itching, blistering, crusting, scaling, and skin sores. 

It is also expected that nausea, vomiting, hypotonicity, and diarrhea would occur if overdosage occurs without causing any toxicity.

Additionally, it may cause nausea and vomiting, or swelling at the injection site.

Other rare side effects include:

• anxiety
• blurred vision
• chills
• cold sweats
• coma
• confusion
• cool, pale skin
• depression 
• vertigo
• dry mouth 
• tachycardia
• flushed, 
• fruit-like breath odor
• increased hunger
• increased thirst
• increased urination
• shakiness
• slurred speech
• sweating
• trouble breathing
• unusual tiredness or weakness

 How to naturally increase glucagon levels

There is little research that has been done on the matter of how to increase glucagon levels naturally. However, it is presumed that the surest way to control glucagon levels is through diet.

This is done by reducing the intake of calories and, as such, forcing the body to secrete glucagon to use glycogen and fat. This is beneficial, especially for those who are trying to lose weight.

Therefore, a diet rich in proteins and fewer carbohydrates and lipids will lead to raised glucagon levels. Additionally, exercising can increase your glucagon levels just as well as fasting.

Conclusion

In summary, glucagon is an essential hormone involved in the regulation of blood sugar and is produced in response to hypoglycemia. 

It mainly affects its function through the liver by increasing glycolysis and gluconeogenesis while shutting down glycogenesis. This process then led to raised blood sugar levels. 

While there is a synthetic type of hormone, it is not commonly used unless there is an emergency.

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