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I heard somewhere that as opposed to other cells, neurons do not use insulin to get their sugar supply.
Why is that?
What is the alternative mechanism? I assume sugar can't just enter the cell without some kind of help from a protein, is that true?
Insulin is not directly involved in sugar uptake. It accelerates sugar uptake by upregulating glucose transporters and activating glycogenesis.
Neurons have many glucose transporters including GLUT1 and GLUT3 which are responsible for glucose uptake.
Moreover, insulin being an endocrine molecule has effects throughout the body including neurons. So neurons need not secrete insulin.
Most non-autotrophic cells are unable to produce free glucose because they lack expression of glucose-6-phosphatase and, thus, are involved only in glucose uptake and catabolism. Usually produced only in hepatocytes, in fasting conditions, other tissues such as the intestines, muscles, brain, and kidneys are able to produce glucose following activation of gluconeogenesis.
In Saccharomyces cerevisiae glucose transport takes place through facilitated diffusion.  The transport proteins are mainly from the Hxt family, but many other transporters have been identified. 
|Snf3||low-glucose sensor repressed by glucose low expression level repressor of Hxt6|
|Rgt2||high-glucose sensor low expression level|
|Hxt1||Km: 100 mM,  129 - 107 mM ||low-affinity glucose transporter induced by high glucose level|
|Hxt2||Km = 1.5  - 10 mM ||high/intermediate-affinityglucose transporter induced by low glucose level |
|Hxt3||Vm = 18.5, Kd = 0.078, Km = 28.6/34.2  - 60 mM ||low-affinity glucose transporter |
|Hxt4||Vm = 12.0, Kd = 0.049, Km = 6.2 ||intermediate-affinity glucose transporter |
|Hxt5||Km = 10 mM ||Moderate glucose affinity. Abundant during stationary phase, sporulation and low glucose conditions. Transcription repressed by glucose. |
|Hxt6||Vm = 11.4, Kd = 0.029, Km = 0.9/14,  1.5 mM ||high glucose affinity |
|Hxt7||Vm = 11.7, Kd = 0.039, Km = 1.3, 1.9,  1.5 mM ||high glucose affinity |
|Hxt8||low expression level |
|Hxt9||involved in pleiotropic drug resistance |
|Hxt11||involved in pleiotropic drug resistance |
|Gal2||Vm = 17.5, Kd = 0.043, Km = 1.5, 1.6 ||high galactose affinity |
GLUTs are integral membrane proteins that contain 12 membrane-spanning helices with both the amino and carboxyl termini exposed on the cytoplasmic side of the plasma membrane. GLUT proteins transport glucose and related hexoses according to a model of alternate conformation,    which predicts that the transporter exposes a single substrate binding site toward either the outside or the inside of the cell. Binding of glucose to one site provokes a conformational change associated with transport, and releases glucose to the other side of the membrane. The inner and outer glucose-binding sites are, it seems, located in transmembrane segments 9, 10, 11  also, the DLS motif located in the seventh transmembrane segment could be involved in the selection and affinity of transported substrate.  
Each glucose transporter isoform plays a specific role in glucose metabolism determined by its pattern of tissue expression, substrate specificity, transport kinetics, and regulated expression in different physiological conditions.  To date, 14 members of the GLUT/SLC2 have been identified.  On the basis of sequence similarities, the GLUT family has been divided into three subclasses.
Class I Edit
Class I comprises the well-characterized glucose transporters GLUT1-GLUT4. 
|GLUT1||Is widely distributed in fetal tissues. In the adult, it is expressed at highest levels in erythrocytes and also in the endothelial cells of barrier tissues such as the blood–brain barrier. However, it is responsible for the low level of basal glucose uptake required to sustain respiration in all cells.||Levels in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels. GLUT1 expression is upregulated in many tumors.|
|GLUT2||Is a bidirectional transporter, allowing glucose to flow in 2 directions. Is expressed by renal tubular cells, liver cells and pancreatic beta cells. It is also present in the basolateral membrane of the small intestine epithelium. Bidirectionality is required in liver cells to uptake glucose for glycolysis and glycogenesis, and release of glucose during gluconeogenesis. In pancreatic beta cells, free flowing glucose is required so that the intracellular environment of these cells can accurately gauge the serum glucose levels. All three monosaccharides (glucose, galactose, and fructose) are transported from the intestinal mucosal cell into the portal circulation by GLUT2.||Is a high-frequency and low-affinity isoform. |
|GLUT3||Expressed mostly in neurons (where it is believed to be the main glucose transporter isoform), and in the placenta.||Is a high-affinity isoform, allowing it to transport even in times of low glucose concentrations.|
|GLUT4||Expressed in adipose tissues and striated muscle (skeletal muscle and cardiac muscle).||Is the insulin-regulated glucose transporter. Responsible for insulin-regulated glucose storage.|
|GLUT14||Expressed in testes||similarity to GLUT3 |
Classes II/III Edit
- (SLC2A5), a fructose transporter in enterocytes (SLC2A7), found in the small and large intestine,  transporting glucose out of the endoplasmic reticulum - (SLC2A9) (SLC2A11)
Most members of classes II and III have been identified recently in homology searches of EST databases and the sequence information provided by the various genome projects.
The function of these new glucose transporter isoforms is still not clearly defined at present. Several of them (GLUT6, GLUT8) are made of motifs that help retain them intracellularly and therefore prevent glucose transport. Whether mechanisms exist to promote cell-surface translocation of these transporters is not yet known, but it has clearly been established that insulin does not promote GLUT6 and GLUT8 cell-surface translocation.
Discovery of sodium-glucose cotransport Edit
In August 1960, in Prague, Robert K. Crane presented for the first time his discovery of the sodium-glucose cotransport as the mechanism for intestinal glucose absorption.  Crane's discovery of cotransport was the first ever proposal of flux coupling in biology.  Crane in 1961 was the first to formulate the cotransport concept to explain active transport. Specifically, he proposed that the accumulation of glucose in the intestinal epithelium across the brush border membrane was [is] coupled to downhill Na+ transport cross the brush border. This hypothesis was rapidly tested, refined, and extended [to] encompass the active transport of a diverse range of molecules and ions into virtually every cell type. 
Cells use sugars to communicate at the molecular level
The human body is made up of 30 to 40 million cells, a large and complex network of blood cells, neurons, and specialized cells that make up organs and tissues. Until now, figuring out which mechanisms control communication between them has proven a significant challenge for the field of cell biology.
Research led by Virgil Percec in Penn's Department of Chemistry, in collaboration with the University's departments of cell and developmental biology and biology, and with Temple and Aachen Universities, provides a new tool to study synthetic cells in incredible detail. Percec and his group demonstrated the value of their method by looking at how a cell's structure dictates its ability to communicate and interact with other cells and proteins. They found that sugar molecules play a key role in cellular communication, serving as the "channels" that cells and proteins use to talk to one another. They published their findings this week in the journal Proceedings of the National Academy of Sciences.
"Ultimately, this research is about understanding how cell membranes function," says Percec. "People try to understand how human cells function, but it is very difficult to do. Everything in the cell is liquid-like, and that makes it difficult to analyze it by routine methods."
Cell biologists have historically used diffraction to study cells. This involves breaking them apart and taking atomic-level pictures of individual parts, such as proteins. The problem with this approach, however, is that it doesn't allow for study of the cell as a whole. Newer methods like fluorescence microscopy allow researchers to study entire cells, but these tools are complicated and don't provide the high-resolution view that diffraction can.
Using engineered synthetic cells as a model system, lead author Cesar Rodriguez-Emmenegger, a former member of Percec's group, now at Aachen, discovered a way to directly study cell membranes using a method called atomic force microscopy. This approach generates extremely high-resolution scans that reveal shapes and structures at a scale of less than a nanometer, nearly 10,000 times smaller than the width of a human hair. Percec's group then built a model that computes how the structural images relate to the cell's function.
The study is the first example of a diffraction-like method that can be done on whole synthetic cells. Using this new method, Percec's group discovered that a lower concentration of sugars on a cell membrane's surface led to increased reactivity with proteins on the membranes of other cells.
One of Percec's goals is to figure out how to control cell-to-cell communication and cell function, which is linked with his group's ongoing work in creating hybrid cells made up of parts of human and bacterial cells. While his group has been studying cell membrane mimics and engineered systems since 2010, the discovery of this new diffraction-like method was, as Percec describes, a "lucky accident."
"We approach problems that other people say there is no solution for. You cannot make a big breakthrough overnight,"Percec says. "All these people on our team are gifted and have the machinery needed to solve the various problems along the way that bring the story together."
How does sugar enter neurons if they don't use insulin? - Biology
Sugar metabolism is the process by which energy contained in the foods that we eat is made available as fuel for the body. The body&rsquos cells can use glucose directly for energy, and most cells can also use fatty acids for energy. Glucose and fructose are metabolised differently, and when they are consumed in excess they may have different implications for health.
Looking at glucose first &ndash when food is consumed, there is a corresponding rise and subsequent fall in blood glucose level, as glucose is absorbed from the gastrointestinal tract into the blood and then taken up into the cells in the body.
Glucose in the blood stimulates the pancreas to release insulin, which then triggers uptake of glucose by cells in the body (e.g. muscle cells) causing blood glucose to return to base levels. Insulin will turn off fat burning and promote glucose burning as the body&rsquos primary fuel source. Any excess glucose ends up being stored as glycogen in the muscles, and it can also be stored as lipid in the fat tissue.
Fructose is also taken up into the blood from the gut, but in this case, the liver serves as a pre-processing organ that can convert fructose to glucose or fat. The liver can release the glucose and fat into the blood or store it as glycogen or fat depots, which, if sugars are consumed in excess, may lead to fatty liver disease and also increase risk for diabetes and cardiovascular disease.
There are also some noted interaction effects between glucose and fructose, in that glucose enables fructose absorption from the gut, while fructose can accelerate glucose uptake and storage in the liver.
If the sugar comes with its inherent fibre (as with whole fruit) then up to 30% of this sugar will not be absorbed. Instead, it will be metabolised by the microbes in the gut, which may improve microbial diversity and help prevent disease. The fibre will also mean a slower rise in blood glucose, which has shown to have positive health effects.
It is easy to over-consume sugar
It is easy to over-consume sugar in juice and sweet drinks, as they contain mostly water and sugar. One glass of orange juice can contain concentrated sugar from five or six whole oranges. And while it is easy to drink that much sugar, you would be less likely to eat that many oranges in one go.
Fizzy drinks do not make you feel full as quickly as foods do. This makes them easy to over-consume. And a small fizzy drink contains nine teaspoons of added sugar, so drinking just one can means that you have almost reached your recommended maximum intake for that whole day.
A broad term meaning any bodily process in which the liver is injured or does not work as it is supposed to. In this website we focus on liver diseases in which the diet hurts the liver
Any sugar added in preparation of foods, either at the table, in the kitchen or in the processing plant. This may include sucrose, high fructose corn syrup and others.
Usually shortened to just diabetes. Sometimes called sugar diabetes. Look at Type 1 Diabetes and Type 2 Diabetes for more information
A type of fat in our body and our food. Three fatty acids are combined with another chemical called glycerol to form a triglyceride.
Sugars are chemicals made of carbon, hydrogen, and oxygen found which taste sweet and are found in food. They are an important part of what we eat and drink and of our bodies. On this site, sugar is used to mean simple sugars (monosaccharides) like fructose or glucose, and disaccharides like table sugar (sucrose). Sucrose is two simple sugars stuck together for example (see Table sugar). Sugars are a type of carbohydrate. Carbohydrates are energy sources for our bodies Sugars enter the blood stream very quickly after being eaten.
Glucose is a sugar we eat. It is found in starch. It is the main fuel for our bodies. It is the sugar measured when we have a blood test to measure the blood sugar.
The pancreas is an internal organ that helps us digest our food by making insulin and other chemicals.
One of the three major groups of nutrients we eat. Much of this website is related to problems associated with too much fat storage in the body. Each gram of fat produces 9 calories of energy if burned by the body as fuel. Fat can be stored in many places in the body. We generally think of fat as under the skin (subcutaneous), but the fat that may be most damaging to us is the fat stored in the liver and around the organs of the abdomen (intrahepatic and visceral or abdominal or intra-abdominal)
A sugar that we eat. Also called fruit sugar. Most fructose comes in sucrose (table sugar, cane sugar, beet sugar), or from high-fructose corn syrup.
The largest internal organ. It weighs about three to four pounds and is located under the lower edge of the ribs on the right side. It helps us digest our food and remove toxins from our blood. "Hepat" in a word means liver, so an "hepato-toxin" is a liver poison or something that can cause damage to the liver
Insulin is a messenger released from the pancreas after eating, which shunts energy (glucose or triglycerides) from the blood into fat cells for storage. Insulin is given to some people with diabetes to lower the blood glucose it leaves the blood and enters the fat cell for storage.
SugarScience is the authoritative source for evidence-based, scientific information about sugar and its impact on health.
Digesting Real vs. Artificial Sugars
When we eat sugar, it moves from the digestive system into the bloodstream, increasing our blood sugar levels. The pancreas has the job of secreting hormones (such as insulin) into the blood to regulate our blood sugar levels. The pancreas is like a factory that turns sugars into something our bodies can use, and the factory slows down when the sugar or sweetener does not give us much energy. Artificial sweeteners do not increase blood sugar levels or insulin production, like real sugars do. This causes the pancreas to respond differently to the artificial sugars, because they give the pancreas nearly nothing to respond to. The consumption of artificial sweeteners can therefore lead to abnormal pancreas functioning and insulin levels, in addition to changes in other functions that affect our metabolism, which may put us at risk for related illnesses such as type 2 diabetes.
We all have microorganisms in our digestive systems that help break down the food we eat. Together, they are called the gut microbiota. The gut microbiota react differently to artificial sweeteners than to real sugar. These organisms become less able to break down real sugars the more that they are exposed to artificial sweeteners. A study conducted on mice showed that consumption of an artificial sweetener led to changes in the gut microbiota that decreased the ability of the mice to digest sugars [ 5 ]. Not being able to break down sugars is a bad thing, because this change in the microbiota can change the amount of nutrients are bodies are able to take out of the food we eat. This means that we might not get the vitamins and minerals that we need, even when we do eat the right foods.
Why Insulin, Not Glucose, Matters Most for Type 2 Diabetes
Dr. Benjamin Bikman made this forceful comparison during the second annual Metabolix conference. The conference is online this year, but is otherwise based in Israel it is dedicated to fixing global metabolic health.
Dr. Benjamin Bikman
Dr. Bikman is a widely recognized expert on insulin resistance. He is a professor of Physiology & Developmental Biology at Brigham Young University. His talk at Metabolix 2021—“Flipping the Switch: From Insulin Resistance to Diabetes”—discussed the precise changes that occur during the transition from mere insulin resistance and pre-diabetes to fully fledged Type 2 diabetes.
He is not the first expert to question the use of exogenous insulin in patients with T2D—Dr. Mariela Glandt, an ASweetLife contributor and one of the organizers of the Metabolix conference, has raised similar questions. Dr. Bikman’s stature in the field, and the boldness of his delivery, make his claim especially notable.
The Glucocentric Paradigm
Dr. Bikman described Type 2 diabetes as “a disease of insulin resistance” that is unfortunately defined and diagnosed by measuring blood glucose instead of insulin resistance itself. As a result, the entire condition is typically viewed through a “glucocentric paradigm,” an erroneous perspective that has unfortunate consequences for the millions of people living with it.
“The problem is that the true lethality of diabetes is not based on the glucose. I’m not saying the glucose isn’t relevant… But the true killers are really derivative of insulin.”
Insulin resistance, the fundamental root cause of Type 2 diabetes, is less frequently considered than blood glucose. Blood sugar is quick and easy to measure, and is almost universally used to evaluate the progression of the disease and the effectiveness of its treatment. Many doctors therefore incorrectly target reductions in blood glucose as the ultimate goal of therapy, and prioritize a lower glucose “at any cost.” By far the most powerful glucose-lowering remedy is insulin. Inevitably, doctors end up “increasing insulin to superphysiological levels,” which will lower glucose in the short term, but significantly exacerbate the fundamental dysfunction that led to diabetes in the first place.
“Insulin therapy in a diabetic makes insulin resistance worse. When we give a patient with Type 2 diabetes insulin, we are making them fatter and sicker than they were before.”
Insulin Resistance & Pre-Diabetes
Unfortunately, the glucocentric paradigm has consequences in the very first stages of the progression of Type 2 diabetes: “our failure to measure insulin itself means that we fail to detect insulin resistance in its earliest stages.”
Type 2 diabetes is ultimately diagnosed after glucose levels have become persistently elevated. This may be the first moment that a doctor notices a patient’s metabolic issues, but in fact rising blood glucose is only one of the later stages of a long disease progression. The average patient newly diagnosed with T2D has probably already been suffering from growing insulin resistance, and its cascading effects, for years.
Even before a person has identifiable pre-diabetes, they may have higher insulin levels than normal, a condition that is almost never identified during a routine checkup. While at this early stage the body is able to make extra insulin to compensate for insulin resistance, those elevated insulin levels will simply accelerate the decline of insulin sensitivity. “Any incessant stimulus to a cell will result in resistance to that stimulus.”
Dr. Bikman contends that insulin resistance starts in the fat cells. Insulin-resistant fat cells become enlarged and overstuffed, and begin to leak cytokines and other inflammatory substances throughout the body. Insulin resistance spreads. By the time that blood glucose levels have started to rise, “insulin resistance has spilled into three other tissues: the muscle, liver and pancreas.”
When these new tissues begin to develop insulin resistance, the disease progression really snowballs. The muscles, “the main consumer of glucose,” lose their ability to take up glucose in the bloodstream. The liver, which typically stores glucose in the form of glycogen, begins to do the very opposite, releasing glycogen when it’s not needed. And in the pancreas, when Alpha cells become insulin resistant, they release another form of stored glucose, glucagon. All of these dysfunctions have the same effect: to raise blood glucose.
This summary barely scratches the surface of what’s going on. “Literally every cell has an insulin receptor,” and a great many more than the tissues mentioned above will begin to malfunction when touched by insulin resistance. The bottom line, in Dr. Bikman’s view, is that the primary cause of Type 2 diabetes—the one necessary condition that sets off this long and incredibly complicated chain reaction—is heightened levels of insulin.
How to Fix Insulin Resistance
“I strongly believe that the best way to lower insulin resistance is to lower insulin itself.”
Dr. Bikman advocates for the use of a low-carbohydrate diet to naturally lower the levels of insulin in the body. Carbohydrates are by far the one stimulus that most reliably and dramatically sparks insulin production. Eating fewer carbohydrates simply and immediately reduces insulin levels throughout the body.
He shared the results of several studies pitting low-carb diets against traditional low-fat or calorie restricted diets. In these experiments, the low-carb diet resulted in marvelous improvements in both fasting insulin level and insulin resistance. The low-fat diet showed no such success, and sometimes quite the opposite: “We’ve known for 30+ years that the conventional dietary advice for diabetics may make the situation worse.”
Dr. Bikman is doubtful about the use of pharmaceuticals for Type 2 diabetes: “We should never look to a drug to solve insulin resistance or Type 2 diabetes, in my mind.” Metformin and low-dose anti-inflammatory pills (such as aspirin) can help with Type 2 diabetes, as well, but “metformin is only half as effective as even modest lifestyle strategies.”
We were lucky enough to interview Dr. Bikman last year upon the release of his book, Why We Get Sick, and can recommend his book for more detail on how insulin resistance affects our health, and how to avoid it.
Ross Wollen is a chef and writer based in Maine's Midcoast region. Before moving East, Ross was a veteran of the Bay Area restaurant and artisanal food scenes he has also worked as a food safety consultant. As executive chef of Belcampo Meat Co., Ross helped launch the bone broth craze. Since his diagnosis with Type 1 diabetes in 2017, he has focused on exploring the potential of naturally low-carb cooking.
Insulin and the Liver
A great deal of glucose absorbed into the bloodstream is put into liver cells, also known as hepatocytes. The hepatocytes have the primary responsibility of turning the glucose into its storage form, a long polymer known as glycogen.
Insulin affects the liver in several ways. It causes the activation of hexokinase, which is an enzyme that phosphorylates glucose so that it becomes unable to leave the cells. Insulin also activates other enzymes necessary for the storage of glycogen in the liver. Two of these enzymes are called glycogen synthase and phosphofructokinase. In its general role on the liver, insulin is responsible for the storage of glucose within the liver.
How Insulin Works
Insulin is the energy-storage hormone. After a meal, it helps the cells use carbs, fats, and protein as needed, and to store what's left (mainly as fat) for the future. The body breaks these nutrients down into sugar molecules, amino acid molecules, and lipid molecules, respectively. The body also can store and reassemble these molecules into more complex forms.
Blood sugar levels rise when most foods are consumed, but they rise more rapidly and dramatically with carbohydrates. The digestive system releases glucose from foods and the glucose molecules are absorbed into the bloodstream. The rising glucose levels signal the pancreas to secrete insulin to clear glucose from the bloodstream.
To do this, insulin binds with insulin receptors on the surface of cells, acting like a key that opens the cells to receive glucose. Insulin receptors exist on almost all tissues in the body, including muscle cells and fat cells.
Insulin receptors have two main components—the exterior and interior portions. The exterior portion extends outside the cell and binds with insulin. The interior portion then signals the cell for glucose transporters to go out and receive the glucose. As blood sugar and insulin levels decrease, the receptors empty and the glucose transporters go back into the cell.
When the body is functioning normally, the glucose derived from ingested carbohydrates gets cleared rapidly through this process. However, when there's no insulin or very low levels of insulin, this doesn't happen, leading to sustained high blood glucose levels.
Excess blood sugar also results when cells aren't able to use insulin properly. Insulin resistance can be due to a problem with the shape of the insulin (preventing receptor binding), not having enough insulin receptors, signaling problems, or glucose transporters not working properly. In addition, insulin resistance can occur as a result of excess body fat.
Insulin has a major effect on fat metabolism. After a meal, insulin causes "extra" ingested fats and glucose to be stored as fat for future use. Insulin also plays a key role in liver function and fat cells.
Insulin stimulates the creation and storage of glycogen from glucose. High insulin levels cause the liver to get saturated with glycogen. When this happens, the liver resists further storage.
Then, glucose is used instead to create fatty acids that are converted into lipoproteins and released into the bloodstream. These break down into free fatty acids and are used in other tissues. Some tissues use these to create triglycerides.
Insulin stops the breakdown of fat and prevents the breakdown of triglycerides into fatty acids. When glucose enters these cells, it can be used to create a compound called glycerol.
Glycerol can be combined with the excess free fatty acids from the liver to make triglycerides. This can cause triglycerides to build up in the fat cells.
Insulin helps the amino acids in protein to enter cells. Without adequate insulin production, this process is hindered, making it difficult to build muscle mass.
Insulin also makes cells more receptive to potassium, magnesium, and phosphate. Known collectively as electrolytes, these minerals help conduct electricity within the body. In doing so, they influence:
An electrolyte imbalance can be worsened by high blood sugar levels as this can cause excessive urination (polyuria), which makes you lose more water and electrolytes.
Blood Sugar 101
Most of us have heard the term blood sugar bandied around enough that we think we know what it means, but few of us really understand the complexity of the system that makes a steady supply of fuel available to our cells around the clock.
The basic facts are these: All animals have a small amount of a simple sugar called glucose floating around in their bloodstream all the time. This simple sugar is one of two fuels that the cells of the body can burn for fuel. The other is fat. Though you may occasionally eat pure glucose--it's called "dextrose" when it is found in the list of ingredients on a U.S. food label--most of the glucose in your blood doesn't come from eating glucose. It is produced when your digestive system breaks down the larger molecules of complex sugars and starch. Sugars like those found in table sugar, corn syrup, milk and fruit and the starches found in flour, potatoes, rice, and beans all contain chains of glucose that are bonded together with other substances. During digestion, enzymes break these bonds and liberate the glucose molecules which are then absorbed into your bloodstream.
How Blood Sugar is Measured
Blood sugar concentrations are described using a number that describes the weight of glucose that is found in a specific volume of blood. In the U.S. that measurement is milligrams per deciliter, which is abbreviated as "mg/dl." Europeans and almost all researchers publishing in medical journals use a different measurement, micromoles per liter, abbreviated "mmol/L."
You can convert any European measurements you encounter to the American standard by multiplying the mmol/L number by 18. There's a handy converter online that will do this for you automatically. You'll find it at http://www.childrenwithdiabetes.com/converter.htm
If a blood test says that your blood sugar is 85 mg/dl this means that there are 85 milligrams of glucose in every deciliter of your blood. This would mean that each liter of your blood would contain 850 milligrams or .85 of a gram of glucose. The body of typical person weighing 150 pounds contains about 4.7 liters of blood. So if their blood sugar has been measured at 85 mg/dl, at the moment they were measured, they had a total of 4 grams of glucose circulating in their bloodstream. This would be 16 calories worth of glucose or as much glucose as there is in two "Sweetart" brand candy discs.
How Your Blood Sugar Levels are Regulated
However, the concentration of glucose in your blood is never static. Your cells are constantly slurping up that blood glucose and burning it for fuel, forcing your liver and pancreas work full time to replace it. Replacing the glucose removed from your bloodstream is essential. It almost as important as keeping the level of oxygen in your blood just right. This is because your brain requires a small but steady supply of glucose at all times and will stop functioning if it doesn't get it. So sensitive is your brain its need for glucose that if the concentration of glucose in your blood stream goes below 30 mg/dl (1.7 mmol/L) you may become unconscious or even die.
Fortunately, there are a number of robust processes built into your metabolism that prevent this from ever happening. Unless you have one of a few extremely rare tumors that affect your glands or are taking one of the few drugs that cause your body to secrete insulin whether or not it is needed, you need never worry that your blood sugar will ever drop anywhere near low enough to cause unconsciousness. A complex set of metabolic processes orchestrated by your pancreas, liver and brain release a constant stream of glucose into your bloodstream at all times. If the systems that regulate your blood sugar are completely normal, the amount of glucose they release is just enough to replace the glucose your cells have removed and burnt for fuel. If they are not, the amount of glucose released might be more than enough, but it will never be life-threateningly less.
Your body gets this replacement glucose from several different sources. Most of the starch and sugar you eat turns into glucose when it is digested. This glucose goes right from your digestive system your bloodstream. Some of the glucose you can't burn off immediately is converted into a storage form called "glycogen" and stored in your liver and muscles. Average bodies can store about 190 grams of glycogen, though some interesting but long-neglected research has found that some people store a great deal more. That typical 190 grams of glucose is worth 360 calories. The body can draw on it anytime it needs some extra glucose fast.
If you were to burn off all this stored glycogen, your body would still be able to ensure that there was enough glucose circulating in your bloodstream at all times by switching into a mode where most of your cells start burning fat instead of glucose. Then to provide the small amount of glucose that your neurons need, since those brain cells are the only ones in your body that can't burn fat, your liver would transform protein into glucose. This protein might come from protein foods you ate--meat or cheese, for example. But if you were unable to eat, or did not eat enough protein, the protein needed to provide the brain its glucose would be taken from your own muscle tissue. It is because your body can "eat" your muscle tissues in this way that starvation diets and diets that are too low in protein result in a dangerous loss of muscle tissue.
The Fasting and Post-Meal Blood Sugar State
Though blood sugar concentrations fluctuate throughout the day, they can be divided into two basic states. One is the fasting state and the other is the post-meal state. The term "post-meal" is latinized English for "after dining" and refers to the period that follows after you have eaten food.
The Fasting State
You are in the fasting state any time when digestion has been completed. It occurs at night while you sleep. You may also enter the fasting state three hours after you have last eaten. However, if you snack between meals and after dinner you may not re-enter the fasting state while you are awake.
In the fasting state your liver keeps your blood sugar concentration at a normal level by continually releasing small amounts of glucose from the glycogen it has stored after meals or by producing new glucose from protein.
The concentration of the hormone insulin in your blood is the signal which tells the liver whether it needs to dump glucose into the blood. Insulin is released by special cells in the pancreas, the beta-cells, when they sense a rising level of glucose in the blood. When there is no new glucose coming into the blood stream from digestion, little insulin is released.
A normal, healthy liver is also sensitive to insulin levels. The less circulating insulin it senses in the blood stream, the harder the liver will work to put more glucose into the blood. In a healthy person, the liver keeps the fasting blood sugar concentration near 85 mg/dl (4.7 mmol/L) at all times.
The Post-Meal State
You remain in the fasting state until you eat some food containing carbohydrates. After eating, any pure glucose that was present in your food will be absorbed into your bloodstream within fifteen minutes. Other carbohydrates will require digestion. Those that digest quickly--the so-called "high glycemic carbs" like white flour or sugar--typically take between a half hour and an hour enter your bloodstream. Slower acting carbohydrates like whole grains or pasta may take an hour to two or even, in the case of some hard-wheat pastas, three hours to release their glucose into your blood.
During this post-meal state, the concentration of glucose in your blood will begin to rise as the glucose liberated from your food comes pouring in. But in a healthy body, this rise is brief and not very high.
That is because as soon as the concentration of glucose in your body starts to rise, it stimulates the insulin secreting cells in your pancreas, called beta-cells, to produce a large burst of a hormone called insulin. Insulin's function is to activate receptors on your body's cells. This enables these cells to remove the circulating glucose molecules from your bloodstream and either burn them for fuel or store them for future use.
Insulin is powerful stuff. To get an idea of how powerful, consider this. If a person who weighed 140 lbs made no insulin at all, every gram of carbohydrate they ate would raise their blood sugar by 5 mg/dl (.3 mmol/). That means if they were to eat a typical coffee shop bagel which contains about 60 grams of carbohydrate, the glucose in that bagel would raise their blood sugar some 300 mg/dl (16.7 mmol/L). If their fasting blood sugar was a normal 85 mg/dl before they ate that bagel, by the time they had finished digesting it their blood sugar would rise to a whopping 385 mg/dl (21.4 mmol/L).
But in a normal person that doesn't happen. If a person with normal blood sugar control were to check their blood with a portable blood sugar meter every ten minutes throughout the three hours that followed their first bite of that bagel, the highest blood sugar concentration they'd be likely to see would almost certainly be under 140 mg/dl (7.8 mmol/L)--and perhaps a lot lower. This blood sugar peak would probably occur about half an hour after they ate the bagel. By an hour after they'd eaten their bagel their blood sugar would probably have dropped to a value near 100 mg/dl (5.6 mmol/L), though it might even have sunk back even lower, to their fasting value of 85 mg/dl. In any case, two hours after they'd eaten, the whole 60 grams of carbohydrate present in the bagel--an amount that could have raised their blood sugar some 300 mg/dl if they did not produce insulin--would have been hustled off into their cells without making a significant change in their blood sugar concentration. That's what insulin can do.
Diabetic Post-Meal Blood Sugar Response
Now let's look at an example of what happens when a person's blood sugar is not normal. Suzy and Tom both have abnormally high post-meal blood sugars. Both meet the diagnostic criteria for type 2 diabetes, though because Suzy's fasting blood sugar is normal, her doctor would probably tell her that she is normal or perhaps that she is prediabetic. Tom's blood sugar has deteriorated so badly his doctor would diagnose him as diabetic based solely on a fasting test.
If Suzy and Tom were to each eat a bagel containing 60 grams of carbohydrate, about half an hour after they ate that bagel, the concentration of glucose in their bloodstreams would also start to climb. But unlike what happened to our normal person, it would not start coming down half an hour after they ate. Instead, their blood sugar concentrations would go higher and higher until it would eventually reach a peak.
Suzy and Tom would experience differing peak concentrations and they may occur at different times after they eat even though could be diagnosed with the same disorder--Type 2 diabetes. That is because their bodies produce different amounts of insulin and their cells also differ in how well they can respond to that insulin. An hour after eating the bagel, the concentration of glucose in Suzy's blood might rise to 220 mg/dl, while Tom's blood sugar might rise to 275 mg/dl. During the second hour after eating, Suzy's blood sugar might drift down to 180 mg/dl, while Tom's might keep climbing to 340 mg/dl --a value very close to that which a person would reach if their body produced no insulin at all.
During the third hour, Tom's blood sugar might finally start coming down while Suzy's would be close to a normal value. Finally, four long hours after eating the bagel, assuming they'd had nothing else to eat, Suzy might have a blood sugar concentration of 98 mg/dl, which is also the fasting level she noted when she measured her blood sugar the first thing in the morning. Tom's blood sugar might be much higher at 165 mg/dl. This is much higher level than Suzy's fasting level, but it is lower than Tom's fasting level which is a relatively high 175 mg/dl.
Even though Suzy and Tom's post-meal blood sugar values reach levels high enough to be diagnosed as diabetic, they do eventually come back down. Because they end up a lot lower than the 385 mg/dl level their blood sugars would have reached if their bodies did not produce any insulin at all, it's clear that that their bodies are still producing some insulin, though it is just as clear, especially in Tom's case, that insulin is not working very well.
The graph below shows how blood sugar in people like this might behave through and entire day.
This Is Exactly What Happens To Your Body When You Eat A Ton Of Sugar
As mouth-watering as a sugar-laden sundae or icing-topped cupcake is, we should all know by now that sugar isn't exactly healthy. In fact, it may be one of the worst things you can eat (that is, if you're trying to live a long, healthy life).
One study from UC San Francisco actually found that drinking sugary drinks like soda can age your body on a cellular level as quickly as cigarettes. The way the sweet stuff impacts your body is way more complex than just causing weight gain. In fact, when you eat a ton of sugar, almost every part of your body feels the strain—and that's bad news for your health in both the short term and especially the long term.
From an initial insulin spike to upping your chances of kidney failure down the road, this is what really happens in your body when you load up on sugar.
Eating sugar creates a surge of feel-good brain chemicals dopamine and serotonin. So does using certain drugs, like cocaine. And just like a drug, your body craves more after the initial high. "You then become addicted to that feeling, so every time you eat it you want to eat more," explains Gina Sam, M.D., M.P.H., director of the Gastrointestinal Motility Center at The Mount Sinai Hospital.
"Once you eat glucose, your body releases insulin, a hormone from your pancreas," Dr. Sam explains. The insulin's job is to absorb the excess glucose in the blood and stabilize sugar levels.
Once the insulin does its job, your blood sugar drops again. Which means you've just experienced a sugar rush, and then a drastic drop, leaving you feeling drained. "That's the feeling you get when you've gone to the buffet and you've overdone it, and all you can do is lie on the couch," explains Kristen F. Gradney, R.D., Director of Nutrition and Metabolic Services Our Lady of the Lake Regional Medical Center, and spokesperson for the Academy of Nutrition and Dietetics.
Feeling sluggish all the time, or always being hungry or thirsty can all be signs you've been binging on a little too much sugar. "Your body's physiologic response is to send out enough insulin to deal with all the sugar and that can have a sluggish effect," Gradney explains. "Additionally, if you are only eating simple sugars, you will feel hungry and tired because you are not getting enough of the other nutrients to sustain your energy," like protein and fiber.
The equation is pretty simple: Excess sugar equals excess calories equals excess weight in the form of fat. Not only do high sugar foods pack a ton of calories into a small amount, but they contain almost no fiber or protein—so you often end up eating much more before you feel full. Dangerous cycle. "If you're just eating sugar, you may be gaining weight but still feeling hungry," Gradney says. She adds that you could easily gain a pound over the course of a week from eating one candy bar and one 20-ounce soda (that's 500 extra calories) each day.
Our high-sugar diets are a big part of why more than one-third of American adults are clinically obese.
When you're overweight or obese, your cells can become resistant to the normal effects of insulin (for reasons that aren't 100 percent understood), and struggle to absorb glucose from the blood to use for energy. So your pancreas goes into overdrive to produce more insulin. But despite the excess insulin trying to do its job, the cells still do not respond and accept the glucose—which ends in excess sugar floating around in your bloodstream, with nowhere else to go. Above-normal blood glucose levels is called prediabetes. When blood sugar levels reach even higher, that's type 2 diabetes.
One of the liver's functions is regulating blood sugar levels. Your cells use the glucose in your blood for energy, and your liver takes the excess and stores it in the form of glycogen. When your cells need energy later, like in between meals, the liver will release glucose back into the bloodstream.
"If you exceed this amount, it turns into fatty acids and that's when you get fat deposits in the liver," Sam explains. That can lead to nonalcoholic fatty liver disease, a condition when your body contains more fat than it can metabolize, causing it to accumulate in the liver cells. (Sugar isn't the sole cause, but glycogen storage is a big contributor, as is any sugar-induced weight gain.) "Fatty liver can develop within a five-year period," Gradney explains. But it can happen even quicker based on your dietary habits and genetic predisposition to insulin resistance. If it progresses, it can eventually lead to liver failure down the road. Your love of soda isn't really worth that, is it?
Trying to pump blood full of sugar through blood vessels is basically like pumping sludge through a teeny tiny pipe. "The pipes will finally get tired. That's what happens with your vessels," Gradney explains. So any area relying on small blood vessels can become affected—kidneys, brain, eyes, heart. "It can lead to chronic kidney disease or kidney failure, high blood pressure, and you have an increased risk of stroke if you have high blood pressure."
In addition to slathering on fancy anti-aging serums and SPF, cutting back on sugar can help skin look younger for longer. "The collagen and elastin fibers in the skin are affected by a lot of sugar in the bloodstream," explains dermatologist Debra Jaliman, M.D. Through a process called glycation, glucose attaches to proteins in the body. This includes collagen and elastin, the proteins found in connective tissues that are responsible for keeping skin smooth and taught. Studies have shown glycation makes it harder for these proteins to repair themselves, resulting in wrinkles and other signs of aging.
"The sugar itself doesn't do any damage, but it sets off a chain of events that can," explains Jessica Emery, D.M.D., owner of Sugar Fix Dental Loft in Chicago. "We have bacteria in our mouths that feed on the sugars that we eat when this takes place it creates acids that can destroy tooth enamel. Once the tooth enamel is weakened, you're more susceptible to tooth decay."
Added sugar is packed into so many foods that youɽ never really think about (case and point: ketchup). "We encourage people to read labels and count grams of sugar," Gradney says. According to the Academy, there's no hard and fast recommendation for daily intake, she adds. Good rule of thumb: "Always choose the option that has the least amount of sugar in it. If you have juice or soda, choose water." Choose whole fruits instead of drinking the juice—the sugar content is less concentrated and the fiber helps your body break it down more effectively. And choose whole foods to naturally limit the amount of sugar in your meals. "The more you stay away from processed foods, the better off you'll be."
Unique sugar-sensing neurons work together to prevent severe hypoglycemia in mice.
Keeping blood sugar in balance can be a challenge, especially for people with type 1 diabetes who rely on intensive insulin therapy to prevent blood sugar from going too high. At Baylor College of Medicine, the group of Dr. Yong Xu and his colleagues from other institutions study glucose-sensing neurons in the brain and they have identified a novel neural feedback system in a small brain region that contributes to keeping blood sugar in balance.
An artist’s rendition of brain connections. Image courtesy of NIH Image Gallery.
“Glucose-sensing neurons sense fluctuations in blood sugar levels and respond by rapidly decreasing or increasing their firing activities. This response can trigger changes in behavior to increase glucose levels. For instance, the animals may begin eating,” said Xu, professor of pediatrics-nutrition at Baylor and the USDA-ARS Children’s Nutrition Research Center (CNRC) at Baylor and Texas Children’s Hospital. “Glucose-sensing neurons also can affect the production of hormones such as glucagon that can directly regulate glucose production or uptake by peripheral tissues. It’s a feedback system that keeps the balance of blood glucose.”
Glucose-sensing neurons are found in several brain regions. Xu and his colleagues focused on neurons located in a small area called the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH). Many neurons in this region express estrogen receptor-alpha and respond to glucose fluctuations in the blood, but their functions in glucose metabolism had not been specifically investigated.
A unique population of neurons
The researchers found that neurons in the vlVMH nucleus of murine brains had unique characteristics.
First, Xu and his colleagues were surprised that, while in other VMH subdivisions about half of the neurons were glucose-sensing, in the ventrolateral subdivision all the estrogen receptor-alpha neurons were glucose-sensing. “Just this fact makes this group of neurons quite unique,” said Xu, who also is professor of molecular and cellular biology at Baylor.
They also found that, although all the neurons in this area sense glucose, they do not respond to changes in glucose level in the same way. About half of the neurons are ‘glucose-excited’ – their firing activity increases when they sense high glucose levels and decreases when glucose levels are low. In contrast, the other half of the neurons are glucose-inhibited – they decrease firing when glucose is high and increase it when glucose is low.
“We wondered why these neurons responded in opposite ways to the same glucose challenge,” Xu said.
The researchers combined genetic profiling, pharmacological, electrophysiological and CRISPR gene-editing approaches to look into this question. They investigated the ion channels that each type of glucose-sensing neuron uses to respond to glucose levels. Ion channels are large molecules spanning across the cell membranes of neurons. The channels control the traffic of ions – electrically charged atoms or molecules – in and out of neurons, a process that is crucial for regulating neuronal firing activities.
The researchers found that glucose-excited neurons use a KATP ion channel, but the glucose-inhibited neurons used a different ion channel called Ano4.
The KATP ion channel is well known in our field, but the role of Ano4 ion channel in glucose sensing has never been reported. We have identified a new ion channel that is important for glucose-inhibited neurons,” Xu said.
A coordinated effect regulates blood glucose
In addition, Xu and colleagues identified the neuronal circuits that are involved when glucose-excited and glucose-inhibited neurons respond to low blood glucose levels. They discovered that the circuits were different – glucose-excited neurons project neuronal connections to a brain region that is different from the one reached by glucose-inhibited neurons.
Using optogenetics, a combination of genetic modifications and light to activate specific neuronal circuits, the researchers showed in mice that when glucose-inhibited neurons responded to low glucose levels, they activated a particular circuit, and the result was an increase of blood glucose. On the other hand, when glucose-excited neurons responded to low blood glucose, they inhibited a different circuit, but the result also was an increase in blood glucose levels.
“When the mice were hypoglycemic, these two circuits were regulated in an opposite manner – one was excited while the other was inhibited – but the outcome was the same, bringing blood glucose to normal levels,” Xu said. “This forms a perfect feedback system to regulate blood glucose levels.”
Interestingly, all the neurons in this important group express estrogen receptor-alpha, a well-known mediator of the ovarian hormone, estrogen. In the future, Xu and colleagues want to investigate whether estrogen plays a role in the glucose-sensing process and whether there are gender differences in the functions of these neurons on glucose balance.
Would you like to know more about this work? Find it in the journal Nature Communications.
Other contributors to this work include Yanlin He, Pingwen Xu, Chunmei Wang, Yan Xia, Meng Yu, Yongjie Yang, Kaifan Yu, Xing Cai, Na Qu, Kenji Saito, Julia Wang, Ilirjana Hyseni, Matthew Robertson, Badrajee Piyarathna, Min Gao, Sohaib A. Khan, Feng Liu, Rui Chen, Cristian Coarfa, Zhongming Zhao, Qingchun Tong and Zheng Sun. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, University of Cincinnati, the University of Texas Health Science Center at San Antonio and the University of Texas Health Science Center at Houston.
This work was supported by grants from the NIH (R01 DK114279 and R21NS108091, R01ES027544/DK111436, R01DK100697, R00DK107008 and K01 DK119471), John S. Dunn Foundation and Clifford Elder White Graham Endowed Fund and USDA/CRIS (3092-5-001-059). Further support was provided by American Diabetes Association (1-17-PDF-138 and 1-15-BS-184) and American Heart Association awards (17GRNT32960003 and 19CDA34660335). Single cell transcriptome profiling was conducted at the Single Cell Genomics Core at BCM that is partially supported by shared instrument grant from NIH (S10OD018033, S10OD023469, S10OD025240) and data were analyzed by the BCM Multi-Omics Data Analysis Core (P01DK113954). This work also was partially supported by the Cancer Prevention and Research Institute of Texas (CPRIT, RP170005 and RP180734) and the NCI Cancer Center Support Grant (P30CA125123).