How the Brain Senses Glucose – and Why


When it comes to brain fuel – glucose is king.[1] Glucose is the brain’s primary source of fuel and it is quite narrowly regulated inside our body as a result. This is referred to as glucose homeostasis.[2] There are two key players in this process – insulin and glucagon.[3] These two hormones are kept in balance so that our blood sugar remains stable. When we eat, the ratio of insulin to glucagon is high – which helps to facilitate many postprandial (after meal) processes in the body.[4]

The standard American diet is very high in glucose – meaning it’s high in carbohydrates like bread, pasta, baked goods, and juices.[5] While glucose is the king of brain (and body) fuel, we do also have the ability to fuel our brains with ketone bodies, which is part of why low carb diets are currently exploding in popularity.[6] Heck, even I got in on the action, and wrote a low carb cookbook. (Note that while the Paleo Diet is lower carbohydrate than the standard American diet, at www.thepaleodiet.com, Dr. Loren Cordain and the Editorial Board do not support extreme low-carbohydrate diets like the Ketogenic diet.)

 

How the Body Manages Glucose

The nuts and bolts of how our brain handles glucose is actually very fascinating. To easily explain a very complex situation, it is best to start by describing the various different metabolic states which bring about different activity in the body and brain. For example, when we lack carbohydrates, our liver glycogen stores are rapidly used and fatty acids are then shuttled (from stored fat,) to provide energy via a process called oxidation.[7] These changes rapidly makes the body less reliant on glucose as it addresses the shortage.

Fatty acid oxidation allows the limited supply of glucose to be conserved for the brain – likely a mechanism developed to prevent starvation in our ancestors, during times of food scarcity.[8]

Think of this as a backup fuel system. Our body knows when one fuel is running low or not available, and switches to another energy supply. Taken to an extreme, when carbohydrates are low enough, for long enough, we go into ketosis.[9] The ‘keto flu’ – where we don’t feel very good after removing carbohydrates from our diet – is directly related to this switch in fuel systems.

On the flip side, if we have plenty of carbohydrates, our bodies will choose to store fat and rely on glucose for fuel since our ability to store carbohydrates is limited. This is also why marathon runners carb-load. They want to maximize this limited store and make sure more glucose is available for their bodies to draw upon as they step outside of a normal human activity range. Glycogen stores can be increased temporarily this way, but if you do this repeatedly – without burning the energy – you are very likely to gain weight instead.[10]

But when we really get into the details; how exactly does our brain sense glucose? and why is this important?

Essentially, there are neurons which detect the presence of glucose, and send signals to our brain, alerting the brain to its presence.[11] Since our brain controls our energy balance (as well as our hunger and satiety signaling processes) – the neurons which detect glucose are critically important.[12] But interestingly, these neurons are located outside the blood-brain barrier – not where you might expect.

 

What Happens to the Brain when Glucose Balance is Disrupted?

When glucose gets out of balance, diseases, obesity, and other conditions develop. But how does this happen, if we have glucose sensing neurons? In some cases, cells such as these neurons, can die and this is tightly related to brain disorders and degenerative brain conditions.[13] Also, neurotransmitter synthesis requires glucose, and our brain will simply have extreme issues if glucose levels (or regulation of glucose sensing) is disrupted.[14]

Glucose is actually shuttled from the blood to the brain through GLUT1 transporters on the surface of the brain which allows glucose to cross the blood-brain barrier.[15] This transport is carefully regulated and can be disrupted if the glucose-sensing neurons aren’t functioning appropriately. This can lead to serious issues.

Most glucose in the brain is used for ‘thinking’ and ‘processing’. These are broad terms, but essentially mean that without enough glucose in the brain, we can’t think properly, or process information. This disruption is similar to what is seen when alcohol is consumed, for example.

These processes (and glucose) are very critical for both learning and memory, and one can quickly see how glucose disruption and cell malfunction or cell death can greatly impair our brain’s critical processes.[16]

Glucose is in fact even more critical for other functions. For example, glucose can be used to synthesize glutamate, glycine, aspartate, and other important compounds. This is critical, as these compounds normally cannot easily gain entry directly into the brain, without glucose being used to synthesize them.[17] Another example of the importance of glucose, is autophagy. Autophagy is a greatly important process that “cleans out” dying or misfunctioning cells. It can be disrupted by poor glucose metabolism. In the simplest terms, think of it as recycling – but for the body.[18] Just as we recycle to provide better results for the earth – our body has internal mechanisms of recycling, for our own well-being. Glucose is also critical for metabolic coupling – where compounds made in one cell, can be used by a neighboring cell.[19] Think of it as similar to your neighbor borrowing a cup of sugar from you (though hopefully as a Paleo Dieter, you’re not keeping big bags of sugar in your kitchen.)

About 50 percent of all glucose in the body is used by the brain – which helps explain the ‘hangry’ state that we all experience.[20] If there isn’t glucose in the brain – neurotransmitters are not produced. This means neurons can’t talk to each other and helps explain our confusion and foul mood when our blood sugar gets very low.

Interestingly, research has also shown a direct link between too much sugar (specifically fructose) – and premature aging. Other studies have shown that too much glucose can be linked to cognitive decline and memory issues.[21] This research is the most frequently cited when articles claim that ‘sugar can kill us’, or ‘sugar can cause Alzheimer’s’. Type 2 diabetes is of course known as the disease where our bodies simply become resistant to insulin – truly scary.

Glucose sensing in the brain is critically important, and a Paleo Diet® will keep glucose levels at normal, healthy levels – leading to much better brain health and a healthier life overall.

 

References

  1. Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci. 2013;36(10):587-97.
  2. Tups A, Benzler J, Sergi D, Ladyman SR, Williams LM. Central Regulation of Glucose Homeostasis. Compr Physiol. 2017;7(2):741-764.
  3. Kalra S, Gupta Y. The Insulin:Glucagon Ratio and the Choice of Glucose-Lowering Drugs. Diabetes Ther. 2016;7(1):1-9.
  4. Kalra S, Gupta Y. The Insulin:Glucagon Ratio and the Choice of Glucose-Lowering Drugs. Diabetes Ther. 2016;7(1):1-9.
  5. Sartorius K, Sartorius B, Madiba TE, Stefan C. Does high-carbohydrate intake lead to increased risk of obesity? A systematic review and meta-analysis. BMJ Open. 2018;8(2):e018449.
  6. Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev. 1999;15(6):412-26.
  7. Purdom T, Kravitz L, Dokladny K, Mermier C. Understanding the factors that effect maximal fat oxidation. J Int Soc Sports Nutr. 2018;15:3.
  8. Houten SM, Wanders RJ. A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation. J Inherit Metab Dis. 2010;33(5):469-77.
  9. Miller VJ, Villamena FA, Volek JS. Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health. J Nutr Metab. 2018;2018:5157645.
  10. Ma Y, Olendzki B, Chiriboga D, et al. Association between dietary carbohydrates and body weight. Am J Epidemiol. 2005;161(4):359-67.
  11. Burdakov D, Luckman SM, Verkhratsky A. Glucose-sensing neurons of the hypothalamus. Philos Trans R Soc Lond, B, Biol Sci. 2005;360(1464):2227-35.
  12. Routh VH. Glucose sensing neurons in the ventromedial hypothalamus. Sensors (Basel). 2010;10(10):9002-25.
  13. Hotchkiss RS, Strasser A, Mcdunn JE, Swanson PE. Cell death. N Engl J Med. 2009;361(16):1570-83.
  14. Bak LK, Schousboe A, Sonnewald U, Waagepetersen HS. Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons. J Cereb Blood Flow Metab. 2006;26(10):1285-97.
  15. Morgello S, Uson RR, Schwartz EJ, Haber RS. The human blood-brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes. Glia. 1995;14(1):43-54.
  16. Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci. 2013;36(10):587-97.
  17. Hertz L, Rothman DL. Glucose, Lactate, β-Hydroxybutyrate, Acetate, GABA, and Succinate as Substrates for Synthesis of Glutamate and GABA in the Glutamine-Glutamate/GABA Cycle. Adv Neurobiol. 2016;13:9-42.
  18. Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol. 2010;221(1):3-12.
  19. Steinman MQ, Gao V, Alberini CM. The Role of Lactate-Mediated Metabolic Coupling between Astrocytes and Neurons in Long-Term Memory Formation. Front Integr Neurosci. 2016;10:10.
  20. Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci. 2013;36(10):587-97.
  21. Calsolaro V, Edison P. Alterations in Glucose Metabolism in Alzheimer’s Disease. Recent Pat Endocr Metab Immune Drug Discov. 2016;10(1):31-39.

*You can unsubscribe at anytime

Comments to this website are moderated by our editorial board. For approval, comments need to be relevant to the article and free of profanities and personal attacks. We encourage cordial debates for the betterment of understanding and discovery. Comments that advertise or promote a business will also not be approved, however, links to relevant blog posts that follow the aforementioned criteria will be allowed. Thank you.

Leave a Reply

Your email address will not be published. Required fields are marked *

Affiliates and Credentials