Does the brain use glucose?

In this post we are going to answer the question ‘’Does the brain use glucose?’’ We will explain what glucose is and how the brain uses it to function.

Does the brain use glucose?

Yes, the brain uses glucose. Glucose is the only sugar that feeds the brain, it is its main source of energy.

The brain grows a lot in the first two years of human life and after 5 years of age it grows more slowly until reaching its full size by adolescence. However, although its growth has a limit, its development never ends as it increases and improves the functions it performs throughout life.

For this development and proper functioning, the brain needs fuel in the form of glucose; approximately 5.6mg of glucose per 100g of brain tissue per minute. Glucose is the only sugar that feeds the brain; it is its main source of energy.

The human brain weighs, on average, 1.4 kg, which represents approximately 2% of body weight, and consumes about 20% of the energy produced from glucose. This is equivalent to consuming between 5 and 10 g of glucose per hour, being able to reach the amount of 140 g per day.

For example, if a medium apple contains 25 g of carbohydrates — including 4 g of fiber, 4 g of glucose, 4 g of sucrose, and 11 g of fructose — it would be necessary to consume, on average, one apple every four hours to maintain optimum glucose supply to the brain, excluding the energy needs of the rest of the body.

Considering the multiple activities that we must carry out in today’s lifestyle, the fulfillment of which, on average, would require considerable energy expenditure, it is clear that our brain must employ strategies to optimize its energy resources.

Brain metabolism

The metabolism of glucose provides the fuel necessary to cover the physiological functions of the brain through the generation of adenosine triphosphate (ATP), a molecule considered “the universal energy currency”. By breaking the bonds in ATP, stored energy is released, and most of it is used by the brain for information processing.

For example, one of the functions carried out in the human cerebral cortex, in which glucose is used, is the synthesis and release of neurotransmitters that mediate the chemical communication of some 10 billion neurons, with about 50 trillion synapses and, to fulfill this mission, it requires approximately 3.8 x 1,012 ATP molecules for its operation.

On the other hand, when blood glucose levels drop dramatically – due to strenuous physical activity or periods of prolonged fasting; normal situations in our reality so demanding – our body resorts to a strategy: raising the concentration of lactate and ketone bodies in the blood, produced in the liver from fatty acids are used as energy substitutes by the cells of the body.

However, in brain cells, glucose cannot be totally replaced by any energy source, although it can be supplemented.

For this reason, pathological events such as thrombo-embolic occlusion of a cerebral artery or a heart attack can cause serious neuronal damage.

After such an event, in a few minutes, the interruption in the blood supply – which involves the decrease of oxygen and glucose in a specific region of the brain – can manifest itself through loss of vision, impaired language, lack of mobility and, Depending on the duration of the event, it could occur up to an inevitable outcome: brain death.

Our brain and its strategy to regulate glucose supply

The brain has relatively low energy reserves, therefore, it depends directly on the caloric intake in the diet; Therefore, it requires a cerebral blood flow that supplies oxygen and glucose to the different brain regions, according to the level of neuronal activity: those regions that demand a greater energy supply are irrigated by a greater number of arteries.

Neurons are highly intolerant of inadequate energy supply and require fine regulation of glucose supply; therefore, the brain monitors blood glucose levels, maintaining a balance in the secretion of peptides that induce the sensation of satiety such as pro-opiomelanocortin and those that stimulate food intake such as neuropeptide.

These molecules are secreted by the hypothalamus, which is the neuronal system in charge of detecting, integrating and regulating glucose homeostasis.

Through stimulation of the vagus nerve and its connection with the gastrointestinal tract, adipose tissue, pancreas, and liver, the hypothalamus manages to modulate the transport, synthesis, storage, and metabolism of glucose in the body.

This is how our brain has perfect control of its resources.

Regulation system

In addition, the brain has adaptive systems that allow it to survive in reduced energy conditions for short periods. In animal models, intermittent energy restriction has been shown to stimulate neuroplasticity and cellular resistance to stress.

For example, it has been observed that some regions of the brain, when affected by energy restriction from diet and aerobic exercise, present changes in the expression pattern of proteins that participate in functions such as communication between neurons, which involves a structural and functional re-organization.

In this way, the functioning of the brain is optimized, making it more suitable not only for periods of energy shortage, but for its usual activity.

Low supply

Our brain is also exposed to a wide variety of diseases when the energy supply is low; therefore, it is vital to keep glucose levels at an adequate level. When they fall below half of the normal values, it is possible to appreciate mental confusion and even reach a coma.

In addition, the effects of an inadequate supply of glucose are not always observed immediately, there are chronic pathologies that are a consequence and, sometimes, cause of the imbalance of the energy metabolism of glucose in the central or peripheral nervous system.

Hence the insistence of nutritionists to maintain a diet rich in carbohydrates that promotes health and brain activity.

How does glucose enter our brain?

In all organs, glucose entry into cells is through specialized transporter proteins. In most tissues, glucose transporters move toward the cell membrane in response to increased insulin in the blood.

Since, in the tissue, the glucose concentration is 20% lower than that of the blood, the flow of glucose through the transporter occurs by diffusion facilitated in favor of its concentration gradient.

An interesting fact is that brain cells do not need insulin to capture glucose, because insulin transporters in the brain are regulated differently and are permanently located in the cell membrane.

Therefore, even in situations in which the glucose concentration is altered as occurs in diseases such as diabetes, due to which insulin levels are decreased, brain cells continue to receive an adequate supply of glucose; Of course! As long as the blood contains a glucose concentration within normal values.

The answer: GLUT1 and GLUT3 glucose transporters in the brain

The cells of the cerebral vascular endothelium that form the capillaries in the brain represent the first glucose capture mechanism. These cells use transporters called GLUT1 —proteins that allow glucose to pass into the cell — where it is normally found in the blood in concentrations higher than those in the tissues.

Next, astrocytes participate, which spread, surrounding the capillaries with structures called sucking feet. These cells also use GLUT1 and participate in the assimilation and subsequent distribution of glucose, as well as other metabolites, to neurons.

On the other hand, it has been suggested that glucose can also diffuse from endothelial cells through the extracellular spaces to neurons.

The latter, unlike astrocytes and the endothelium, express the GLUT3 transporter, which has a higher affinity for glucose and transport it at a higher rate, even in situations where there is a low glucose level.

In this way, it is ensured that neurons have an adequate supply of glucose to cover their activities, even in stressful situations.

Astrocytes and their role as nurse cells in the brain

Normally, glucose is completely oxidized and converted to CO? and water, through glycolysis, the Krebs cycle, and the mitochondrial respiratory chain.

On the contrary, in the absence of oxygen, the partial oxidation of glucose produces lactate, a molecule that can also be used as fuel in the Krebs cycle and that improves the generation of ATP in these circumstances.

In fact, neurotransmission by glutamate (the most abundant neurotransmitter in the mammalian brain) has been proposed to stimulate the release of lactate by astrocytes. These cells produce lactate from their glycogen stores, which is subsequently captured by neurons through monocarboxylate transporters.

In other words, when neuronal activity increases and, therefore, their metabolic requirements increase, astrocytes also increase lactate release.

This release aims to supply an additional energy substrate to neurons, keeping them in favorable energy conditions, avoiding metabolic stress.

Since astrocytes detect activity and, therefore, neuronal requirements, it is possible that the release of glutamate by neurons stimulates the synthesis of GLUT3, thereby increasing glucose uptake in astrocytes. If it occurs in this way, glycolysis and synthesis of lactate will be favored, which will be transferred to neurons to be used as an energy substrate in reduced oxygen conditions.

In the case of neurogenerative diseases such as Alzheimer’s, one of the earliest signs of the disease is reduced brain glucose metabolism; Studies in both humans and animals suggest that the alteration in glucose is associated with the progression of the disease.

Additionally, obesity and type 2 diabetes are closely related to Alzheimer’s progression and cognitive decline; glucose deficiency and decreased insulin sensitivity produce a series of alterations in the brain that are very similar to Alzheimer’s.

Understanding these and other processes in experimental models of cerebral infarction will contribute to the knowledge of the cellular and molecular mechanisms that constitute this pathology and, consequently, will favor the identification of therapeutic targets.

FAQS: Does the brain use glucose?

Does the brain use glucose or fat?

For this development and proper functioning, the brain needs fuel in the form of glucose; approximately 5.6mg of glucose per 100g of brain tissue per minute.

Does the brain prefer ketones or glucose?

As its only food, the brain usually runs on glucose. Glucose is not accessible during starvation, and so the brain develops the ability to use an alternative fuel: ketones.

Can the brain use glucose without insulin?

Yes. Insulin is not required for the transport of glucose into most cells of the brain.

What is the best source of glucose for the brain?

Carbohydrates, it is much better to take healthy complex carbohydrates (peas, whole grains, rice, pasta).

Why does the brain only use glucose?

Glucose is the only sugar that feeds the brain, it is its main source of energy. In humans the brain requires approximately 20% of the energy derived from glucose, therefore it is necessary for proper brain function.

In this post we answered the question ‘’Does the brain use glucose?’’ We explained what glucose is and how the brain uses it to function.

If you have any questions or comments please let us know!

References

Berg, J. M., Tymoczko, J. L., & Lubert Stryer. (2013). Each Organ Has a Unique Metabolic Profile. Retrieved November 21, 2020, from Nih.gov website: https://www.ncbi.nlm.nih.gov/books/NBK22436/#:~:text=Brain.,a%20continuous%20supply%20of%20glucose.

Mergenthaler, P., Lindauer, U., Dienel, G. A., & Meisel, A. (2013). Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends in Neurosciences, 36(10), 587–597. https://doi.org/10.1016/j.tins.2013.07.001

Sugar and the Brain. (2020). Retrieved November 21, 2020, from Harvard.edu website: https://neuro.hms.harvard.edu/harvard-mahoney-neuroscience-institute/brain-newsletter/and-brain/sugar-and-brain

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