What Do Counter-Regulatory Hormones Do


Glucose is a major source of energy for our bodily tissues. Particularly, our brain requires a constant supply of glucose to maintain its functions. That said, glucose management holds great significance, and its understanding goes beyond just carbohydrates and insulin.

There are many known factors that can create changes in glucose levels, including hormones that are released in conditions like stress, sickness, or as a result of insulin deficiency itself. These hormones are called counter-regulatory hormones.

Counter-regulatory hormones oppose the function of insulin, meaning they work to raise blood glucose levels. In this article, we discuss the impact of counter-regulatory hormones and their role in the body.

What do counter-regulatory hormones do?

Counter-regulatory hormones are those that act in opposition to the insulin hormone. Our bodies require constant supplies of glucose to maintain bodily functions. This is generally acquired due to a built-in physiological system that regulates blood sugar at constant levels.

However, there are certain circumstances that can create an imbalance in blood glucose levels. Hyperglycemia (high blood sugar) and hypoglycemia (low blood sugar) both refer to glucose imbalance conditions.

Counter-regulatory hormone secretion happens when the expected levels of glucose fall in the body (hypoglycemia). They raise blood sugar levels by promoting the release of stored glucose in the liver and limiting sugar uptake by muscle cells, making the cells resistant to insulin.

The four known counter-regulatory hormones are:

  • Glucagon
  • Epinephrine (also called adrenaline)
  • Cortisol
  • Growth hormone

Since glucose is a major source of fuel for the body, the sufficient uptake of glucose is tightly regulated by a series of hormones and other body responses. For this reason, it is quite uncommon to witness hypoglycemia in normal, healthy individuals. However, it is fairly common in patients with diabetes mellitus, especially those who undergo insulin treatment.1

Counter-regulatory mechanism

In healthy individuals, the counter-regulatory hormones act as a principal defence against low blood sugar.2

Under normal conditions, blood glucose levels are constantly maintained. This is because there's a fine balance between glucose production and its utilisation by the insulin-sensitive tissues (such as the brain and skeletal muscles).

Hypoglycemia typically results from an imbalance between glucose synthesis and utilisation. This can happen when glucose is removed from the bloodstream too quickly or when glucose delivery is faulty—or both. In such conditions, the secretion of counter-regulatory hormones becomes elevated to bring the fall in sugar levels back to normal.1

The first response to falling glucose levels is to limit the secretion of insulin. Insulin is the hormone that is produced by the beta cells of the pancreas. It is mostly responsible for storing blood glucose in the liver for later use. However, when the blood sugar level drops, the signal to store glucose by insulin also decreases. This in turn activates insulin's counterpart, glucagon, and other regulatory hormones.

Glucagon is a hormone that is produced by the alpha cells of the pancreas. It carefully regulates glucose levels in a variety of ways, including:

  • It triggers your liver to convert the stored glucose (glycogen) to its usable content before releasing it into the bloodstream. This process is known as glycogenolysis
  • Glucagon limits the liver's ability to store glucose. This allows glucose to stay in the blood for longer
  • It also regulates your body's ability to process glucose from other sources, such as proteins

Cortisol is released from the adrenal glands situated on the top of both kidneys. Cortisol is released when we experience stress. Moreover, cortisol also promotes the release of fatty acids and glucose from the liver to deal with stress. Additionally, in diabetic patients, stress can also create an imbalance in blood sugar levels. People with diabetes type 2, who have high cortisol levels due to chronic stress, can develop hyperglycemia, which may in turn reduce their sensitivity to insulin.

Epinephrine, or adrenaline, is released from the adrenal glands and nerve endings. Like cortisol, epinephrine plays a role in the fight-or-flight reaction to stress.

It signals the liver to release glucose into the bloodstream and promotes insulin resistance.

Growth hormone (GH) is a protein hormone released from the pituitary gland of the brain. It is involved in major complex body processes and particularly supports growth, body maintenance, repair, and metabolism. It also promotes blood glucose concentration and breaks down fat cells for energy usage.

However, in type 1 diabetes patients, persistently high growth hormone levels can cause insulin resistance.

Counter-regulatory response

The physiological response of counter-regulatory hormones to decreasing glucose concentration (hypoglycemia) is dependent on the following key features:

  • Restricting insulin hormone release as an initial response to low blood sugar levels
  • Secretion of the glucagon hormone to increase blood glucose levels
  • Epinephrine stimulates the liver and kidneys to produce glucose while also acting to limit insulin production
  • Release of cortisol and growth hormone if glucagon and epinephrine are unable to raise adequate amounts of plasma glucose

Moreover, the impact of counter-regulatory hormones in diabetes patients can pose great challenges. Many patients with diabetes type 1 lose their defence against hypoglycemia. Also, for unknown reasons, they tend to lose their ability to secrete glucagon. With their blunted counter-regulatory mechanism, people become significantly more susceptible to bouts of hypoglycemia. The problems of a counter-regulatory response may also develop in type 2 diabetes patients, specifically those taking insulin treatment.

The excessive counter-regulatory response can also cause diabetes ketoacidosis (DKA) - a serious complication that happens when the body does not have sufficient insulin.3

To manage diabetes, it is necessary to understand the proper insulin intake to turn off the rising glucose effects.


Counter-regulatory hormones work against the function of insulin by raising blood sugar levels. They act as a major defence against low glucose levels in healthy individuals. Glucagon, epinephrine, cortisol, and growth hormone are the ones that trigger the liver to release glucose into the bloodstream. Hypoglycemia is most prominent in diabetic patients. The elevated levels of these hormones can trigger insulin resistance in the body.

Counter-regulatory hormones imply a powerful effect on plasma glucose. It is important to understand them in order to manage diabetes properly.


  1. Sprague JE, Arbeláez AM. Glucose counterregulatory responses to hypoglycemia. Pediatric endocrinology reviews : PER [Internet]. 2011;9(1):463–73; quiz 474-5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755377/
  2. Verberne AJ, Sabetghadam A, Korim WS. Neural pathways that control the glucose counterregulatory response. Frontiers in neuroscience. 2014 Feb 26;8:38.
  3. Shahid W, Khan F, Makda A, Kumar V, Memon S, Rizwan A. Diabetic Ketoacidosis: Clinical Characteristics and Precipitating Factors. Cureus [Internet]. 2020 Oct 4;12(10). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606188/
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Sadaf Ahmed

Master of Science - MSc, Physiology, Clinical & Molecular Hematology, Karachi University, Pakistan

Sadaf is an experienced writer who creates a quality and well-researched scripts particularly related to Health Sciences.

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