Control of Blood Glucose Concentration

Our body’s glucose levels fluctuate throughout the day before and after meals. These fluctuations could be very problematic considering glucose is one of the most important molecules that sustains life! As such, to remain healthy it's very important that our body is able to maintain optimal blood glucose concentrations. There are various methods that the body uses to oppose fluctuations of glucose excess or shortage and maintain blood glucose concentration at constant levels.

What is the regulation of Blood Glucose Concentration?

Glucose is a type of carbohydrate or sugar known as a monosaccharide. This small and soluble molecule is the main free circulating sugar in our blood plasma. Glucose is the main source of energy for cell function because it's the primary substrate in glycolysis. Glycolysis is the first metabolic step in cellular respiration in some cells, like human brain cells, necessary in cellular metabolism for generating energy (ATP).

When the glucose concentration gets too low (hypoglycaemia), these cells will be especially vulnerable as they will be unable to perform respiration and, thus, will be deprived of energy and unable to perform their role. A low glucose concentration could result in cell damage and even cell death, which could be very dangerous in brain cells for example, as these can't be replaced and their death would have a drastic impact on our health and survival.

When blood glucose concentration (BGC) gets too high (hyperglycaemia) it can also be very problematic. In this case, the water potential of the blood increases, which means less water would move out of the blood to the tissues and more would enter the blood from the tissues. High glucose concentrations can have severe osmotic complications resulting in frequent urination and severe dehydration. Furthermore, hyperglycaemia can cause damage to the walls of the blood vessels and increase the risk of heart disease, stroke, kidney disease, vision impairment, and nerve problems.

Sources of glucose in the body

There are three main sources of glucose in the body:

• Diet - Glucose is absorbed from our food. It is often obtained after breaking down ingested carbohydrates such as maltose, starch, sucrose, and lactose present in food items like pasta, rice, and fruit.
• Glycogenolysis - Glucose is released from the breakdown of glycogen. This process happens in the liver and muscle cells containing glycogen granules.
• Gluconeogenesis - Glucose is produced from non-carbohydrates sources, including lipids (like glycerol) and amino acids.

To make sure blood glucose concentration levels originating from these different sources remain constant, our body uses hormones that sense concentration changes and act to restore the normal levels. Without this regulation, glucose levels would be very high after a meal and very low just a few hours later as glucose is consumed through respiration which can be very unstable to support normal cell function.

The role of Hormones in Blood Glucose Control

We humans, as well as animals, do not eat continuously. Our diet also varies from meal to meal, and the rate at which we respire glucose differs depending on the body’s mental and physical activity. Due to the fluctuations in supply and demand, three main hormones insulin, glucagon, and adrenaline work together to achieve homeostasis and maintain a constant blood BGC. Insulin and glucagon are both produced by the pancreas, which plays a very important role in blood glucose homeostasis. Adrenaline is produced by the adrenal glands. Together they all act on the liver to help achieve blood glucose homeostasis.

How do Hormones work?

Hormones are chemical messengers of which there are many types of classes. However, they all have some critical features in common. These include:

• Hormones are very potent and are effective at low concentrations.
• They travel via the blood to their target cell (the specific cells on which they act).
• They bind to specific receptors on the target cell (Some hormones bind to their receptor on the target cell membrane, while others bind to the receptor inside the cell)

Adrenaline

Adrenaline is an amine hormone derived from the amino acid tyrosine (Tyr) and released from the adrenal gland. It increases blood glucose levels by stimulating the breakdown of the stored glycogen in the liver to glucose (glycogenolysis) like the glucagon hormone. However, unlike glucagon, adrenaline mediated glycogenolysis is usually triggered by the fight-or-flight response instead of a drop in BCG levels. The fight-or-flight response is an automatic physiological response to a perceived life-threatening situation.

Insulin

Insulin is a globular protein hormone secreted from the β cells in the islets of Langerhans, which is a cluster of cells in the pancreas. During hyperglycaemia, usually after having a meal, the β cells in the islets of Langerhans detect the rise in BGC and in return release insulin into the bloodstream. The insulin specific receptor is expressed in almost all cells (except red blood cells). After binding to insulin, the receptor undergoes conformational changes that lead to the activation of various intracellular cascades of events.

The signalling events triggered by insulin action include:

To sum up, insulin lowers blood glucose concentration mainly by:

• Increasing the glycogenesis rate.
• Increasing the cellular respiration rate. (glucose consumption)
• Increasing the glucose uptake rate in cells. (especially in muscle and liver cells)

Insulin is constantly secreted when the BCG is high because this hormone is automatically broken down in the liver. When the blood glucose levels return to the optimum point, insulin release ceases from β cells in the pancreas. This is an example of a negative feedback system!

Glucagon

Glucagon is another protein hormone released from the pancreas. However, this hormone is produced in α cells of the islets of Langerhans and are released in response to low BGC. Glucagon acts by binding to specific protein receptors on the plasma membrane of liver hepatocytes. After binding, the receptor undergoes a conformational shape and gets activated. The activated receptor protein initiates cascades of events that lead to the activation of a series of enzymes. As a result, more glucose is released into the bloodstream, and the blood glucose levels return to their optimum higher value. The α cells detect this return and halt the release of glucagon.

To sum up, glucagon increases blood glucose concentration mainly by:

• Reducing glucose absorption by liver cells.
• Increasing glycogenolysis rate, meaning the breakdown of glycogen to glucose.
• Increasing gluconeogenesis rate, meaning the production of glucose from amino acids and lipids.

Blood Glucose Concentration Diagram

The two hormones, insulin and glucagon, work in opposite ways (antagonistically) to maintain blood glucose levels stable. They are both released from the pancreas which plays a very role in monitoring and controlling the BGC, and both act on the liver. Other hormones like adrenaline are also involved in the regulation of blood glucose levels. These hormones are susceptible and are controlled by negative feedback. These features allow them to control the BGC at an optimum point. It is also important to mention that since there is often a lag between the release of hormones and their response, the BGCs typically fluctuate within a narrow range at around 5mmol.dm^-3 (in healthy individuals).

Diabetes and the Control of Blood Glucose Concentration

Most certainly you have heard of diabetes disease. Diabetes is a chronic metabolic disease related to the regulation of blood glucose levels. It's estimated that a staggering 422 million people have diabetes worldwide and 1.5 million people die a year from this disease, and both numbers have been steadily climbing.

Diabetes is a disease characterized by hyperglycaemia or high levels of blood glucose concentration. When prolonged, this condition is very dangerous and can lead to a variety of problems including damage to the heart, nerves, blood vessels or eyes.