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Control of Blood Glucose Concentration

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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).

Cellular Respiration is a set of chemical reactions used by cells to produce energy in the form of ATP (Adenosine triphosphate) using sugars and oxygen! To learn more about the steps of this important metabolic process that sustains cell function read our article Respiration!

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.

The body needs to maintain blood glucose levels on average around 5 mmol dm-3 or 90 mg cm-3.

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.

Read our article Osmosis to learn more about how solutes can influence the movement of water molecules!

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.

Glycogen is a carbohydrate (sugar) also known as a polysaccharide, resulting from the polymerization of glucose monosaccharides. Glycogen serves as the main energy reservoir in animal tissue because it's how excess glucose is stored in animal cells.

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.

Role of the liver in Blood Glucose homeostasis

The liver is located on the right side of the body, just below the diaphragm, a thin skeletal muscle at the base of the chest. The liver is mainly composed of hepatocytes (liver cells). In addition to the many other jobs that the liver has in the body, it plays an important role in glucose homeostasis.

Homeostasis is a self-regulation process that ensures the maintenance of steady-state conditions inside any biological system. To learn more about how this is achieved read our article Homeostasis!

The liver is responsible for three critical processes involved in the regulation of blood glucose concentration. It's the organ where Glycogenolysis and Gluconeogenesis happen. In these two events, glucose is either produced from the breakdown of glycogen into glucose or converted from non-carbohydrate sources respectively. Both these events are important when blood glucose levels become too low and need to be replenished. The liver is also the site where Glycogenesis, meaning the production of glycogen from glucose happens. This is relevant in hyperglycaemia, when the BGC becomes too high, the excess glucose is taken up by the liver and stored in the form of glycogen granules.

Gluconeogenesis is especially relevant when the glycogen stores are exhausted during prolonged hunger so Glycogenolysis can no longer happen. Gluconeogenesis in the liver maintains the BGC and prevents it from reaching dangerously low levels.

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)

Hormones are produced by endocrine glands (like the pancreas, the adrenal glands or the thyroid) and are directly secreted into the bloodstream. They are sometimes referred to as the first messengers. In some cases, these hormones bind to their complementary receptor on their target cell and stimulate the production of another molecule which acts as the second messenger inside the cell. This mechanism of action is used by hormones like adrenaline and glucagon.

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.

The mechanism of action of adrenaline can be summarised as follows:

  1. Adrenaline binds to its complementary receptor on the membrane of the liver hepatocytes which triggers a change in the receptor.
  2. The activated receptor causes activation of an intracellular enzyme called Adenylyl cyclase. This enzyme converts ATP to cyclic AMP (cAMP).
  3. The cAMP is the second messenger. It binds to protein kinases, triggering a conformational change in the enzymes which activates them.
  4. The activated protein kinase enzyme accelerates the conversion of glycogen to glucose, facilitating the release of glucose.

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:

  • Activation and increase in the number of glucose transport carrier proteins (GLUT 4 proteins). This results in the increased uptake of glucose via facilitated diffusion. In the absence of insulin, these glucose transporters are stored in the vesicles part of the plasma membrane.
  • Activation of the enzyme that catalyses the conversion of the excess glucose in the cell to glycogen (glycogenesis) and fat.

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!

Negative Feedback systems are homeostatic self-regulation processes whereby changes to a biological system are reversed and returned back to the previous optimal level. Read our article Negative Feedback to learn more about how these systems contribute to Homeostasis!

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.

By 2040, it's expected that half a billion people will suffer from this disease. That's almost the entire population of Europe!

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.

There are two main types of diabetes:

  • Type 1 Diabetes (least common) - People are unable to produce insulin in the pancreas in sufficient quantities or at all. Without insulin, glucose levels remain high after you eat. Glucose can't enter into cells, which results in frequent urination and feeling constantly tired. People with type 1 diabetes depend on regular injections of insulin, they're insulin-dependent.
  • Type 2 Diabetes (most common) - People still produce insulin but not enough or become insensitive to its action rendering it ineffective. This type of diabetes is rapidly growing among the population and it's linked to obesity and physical inactivity. It's less severe than Type 1 diabetes and treatment usually includes diet, exercise as well as other therapeutics.

Read our articles Diabetes and Insulin to learn more about this!

Control of Blood Glucose Concentration - Key takeaways

  • There are three sources of glucose in the body:
    • The diet.
    • The breakdown of glycogen (glycogenolysis).
    • The conversion of sources other than carbohydrates (gluconeogenesis).
  • The three main hormones insulin, glucagon, and adrenaline work together to achieve homeostasis and maintain a constant BGC. The liver is one of these three hormones' main sites of action. It is responsible for glycogenesis, glycogenolysis, and gluconeogenesis.
  • Insulin and glucagon are released from the islets of Langerhans in the pancreas. Glucagon acts on the liver and stimulates glycogenolysis and gluconeogenesis to raise the BCG. Insulin acts on the liver and other tissue cells to stimulate glucose uptake and lower the BCG.

Frequently Asked Questions about Control of Blood Glucose Concentration

Some cells can only respire glucose as their source of energy. Therefore, too low blood glucose levels would be detrimental and damaging to these cells.

On the other hand, too high blood glucose (hyperglycemia) concentration leads to high water potential in the blood. As a result, less water would move from the blood to the tissues which could lead to tissue dehydration and damage. 

As part of food intake, we ingest carbohydrates that get broken down into glucose.

The Respiration of cells and blood osmolality. 

Hypoglycaemia leads to weakness, confusion, sleepiness and eventually passing out.

Also called glycaemia, it’s the amount of glucose (sugar) in the blood.

Final Control of Blood Glucose Concentration Quiz

Question

What is glucose?

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Answer

Glucose is a 6-carbon monosaccharide carbohydrate. It is the main substrate for glycolysis and the source of energy for animal cells.

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Question

What is the area where the endocrine cells in the pancreas are located?

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Answer

The islets of Langerhans.

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Question

Name two types of endocrine cells in the islets of Langerhans and describe what they produce.


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Answer

The islets of Langerhans contain α and β cells, which produce glucagon and insulin respectively

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Question

What are antagonistic hormones?


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Answer

Hormones that work against each other with opposite effects.

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Question

Give an example of a pair of antagonistic hormones? 


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Answer

Insulin and glucagon.

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Question

Name three hormones involved in blood glucose regulation


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Answer

Adrenaline, insulin, and glucagon.

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Question

Name the sources of glucose in animals.


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Answer

Diet, gluconeogenesis, and glycogenolysis

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Question

Define gluconeogenesis.


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Answer

Gluconeogenesis is the process of producing glucose from non-carbohydrate sources such as glycerol and amino acids

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Question

Define glycogenolysis. 


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Answer

Glycogenolysis is the process of the breakdown of glycogen to glucose.

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Question

Define glycogenesis.


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Answer

Glycogenesis is the synthesis of glycogen from glucose.

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Question

What is type I diabetes characterised by?

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Answer

Type I diabetes is an acute onset, usually before 30 years of age. It also includes the destruction of the pancreatic beta cells.

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What is type II diabetes characterised by?

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Answer

Type II is more commonly seen in adults over 30-40 years of age. Insensitivity of insulin receptors on the tissue cells to insulin followed by impaired insulin secretion.

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How is the type I diabetes controlled?


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Answer

Insulin injections, having a healthy lifestyle, and diet control type I diabetes. 

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How is type II diabetes controlled?


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Answer

Low carbs and high fibre diet. Increased physical activity. Treatment may be supplemented by insulin injections, drugs that increase insulin secretion in the body, and/or drugs that reduce glucose absorption in the gut.

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Question

Why is it important to filter the content of the test tubes after reaction with Benedict’s solution? 


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Answer

The reaction produces a white precipitate that may interfere with light absorbance and hence result in inaccurate data.

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What are the early signs of diabetes?


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Answer

Individuals with diabetes often complain of tiredness, and increased thirst and hunger. They also show signs such as hyperglycaemia, presence of glucose in their urine (glycosuria), urinating excessively (polyuria), regular episodes of thrush, weight loss and blurred vision.

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What colour is Benedict’s solution?


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Answer

Blue

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What colour does Benedict’s solution turn into in presence of glucose?       


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Answer

Colourless

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What amount of glucose is normally present in the urine?


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Answer

 zero

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What is a calibration curve?


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Answer

Generating a calibration curve is a generic approach for estimating the concentration of a drug or substance in an unknown sample by comparing it to a collection of standard samples with known concentrations.

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Why do diabetic individuals have a very pale urine?


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Answer

The presence of glucose lowers the water potential in the filtrate and reduces how much water can be reabsorbed from the filtrate in the kidneys producing dilute and pale urine.

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What equation is used in serial dilution?


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Answer

Volume from the stock solution = (Desired concentrion/ Stock concentration)*total volume

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Where is insulin secreted from?


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Answer

Insulin is secreted from the Beta cells of the islets of Langerhans.

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What is the main cause of type I diabetes?


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The main cause of type I diabetes is autoimmune destruction of the beta cells of the islets of Langerhans.

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What is the main cause of type II diabetes?


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The main cause of type II diabetes is poor diet, lack of physical activity, and genetic predisposition.

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Question

what is the average BGC?

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Answer

The body needs to maintain blood glucose levels on average around 5 mmol dm-3 or 90 mg cm-3.

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What is hyperglycemia?

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Answer

High BGC

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What is hypoglycemia?

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Low BGC

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Where is adrenaline produced?

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Answer

Adrenal Glands

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What are the main cells that make up the liver?

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Answer

Hepatocytes

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