Understanding Our Bodies: Insulin

Almost everyone has heard of Insulin. You probably know that people with type 1 diabetes need to inject themselves with insulin to survive, and must constantly monitor the amount of sugar they eat. But what do you really know about insulin? What is its purpose in the body, and why do we need it? How does it relate to our diets? What happens when things go wrong with it? And why should anyone who doesn’t have diabetes give a hoot?

Insulin is one of the most important hormones in the human body, and yet most people don’t really understand why our bodies make it or how what we eat affects the levels of insulin we produce. More so than any other hormone, our diet is key in regulating insulin levels, and thus a number of biological processes. As you’ll soon see, everyone should think about how what they eat impacts their body’s insulin release to be at their happiest and healthiest.

Why We Need Insulin

Every living thing requires energy to survive. In cells, energy is stored and shuttled around using a molecule called Adenosine Tri-Phosphate, or ATP. Whenever the cell then has an energy-requiring reaction, enzymes can use the energy stored in ATP’s phosphate bonds to fuel it. Cells rely on ATP to survive, and to create ATP, they rely on glucose.

All cells, from bacteria and fungi to us, take glucose and use it to generate ATP by a process called Oxidative Phosphorylation. First, glucose is converted to an intermediate molecule called pyruvate via a process called glycolosis. As long as there is oxygen around, this pyruvate is further converted to Acetyl CoA, which enters a cycle of reactions called the Citric Acid Cycle. This takes the carbon to carbon bonds and uses them to create high energy electrons, which are then passed down a chain of enzymes which use the electron’s energy to create a proton gradient, the force of which fuels ATP synthase, the enzyme which creates ATP from ADP. Without glucose, cells cannot create ATP, and eventually die.

In plants, a process called photosynthesis takes light energy from the sun and uses it to combine carbon dioxide (CO₂) and water (H₂O) to create glucose (C₆H₁₂O₆). This means that to survive, all they need is light, air and water. Unlike plants, though, we cannot create our own glucose, so we rely on our diets to provide it for us.

Just about everything we eat is able to be used to create glucose. Carbohydrates, by definition, are sugars, and all sugars are readily converted to glucose. The amino acids that make up proteins can be converted to glucose via an enzymatic process called gluconeogenesis. Fats, too, are converted to glucose or its derivatives; glycerol, for example, can be converted to glucose via gluconeogenesis, and fatty acids can be converted to Acetyl CoA via beta oxidation. No matter where it comes from, the glucose from our meals then ends up in our blood to travel around our bodies to the tissues that need it.

Obviously, having a blood glucose level that is too low would be bad – not enough glucose will get to our various tissues, and our cells won’t be able to generate enough ATP to function. This is a condition known as hypoglycemia, and the effects can range from mildly ‘feeling bad’ to seizures, unconsciousness, permanent brain damage or even death, all of which are due to a lack of ATP. But you can tip the scale too far in the other direction, too. You would think that since it’s so important, we would want a ton of glucose in our blood, but too much causes our blood to thicken, slowing it down and drawing fluid from our tissues to try and make it thin again. Too high of a blood glucose level, called hyperglycemia, can result in blurred vision, fatigue, dry mouth and heart problems that can sometimes be fatal. So our bodies work very hard to maintain our blood glucose levels between 3.6 and 5.8 mM (mmols/liter). This is about enough glucose to provide energy to the body for 20-30 minutes, so as we use up the glucose in our blood, our bodies constantly release more (hopefully) without overdoing it.

It’s particularly important for our bodies to maintain glucose levels every time we eat. Whenever we ingest food, our bodies have to quickly adjust to the sudden flood of glucose entering our systems as our meals are digested. Take something as small as a roll of Smarties, for example. One roll of Smarties contains 6 grams of sugar. At around 125 lbs, my body contains an average of 4 liters of blood. This means that if all the sugar from a single roll of those delicious candies were to enter my bloodstream at once and remain unchecked, it would raise by blood sugar by 8 mM! Four smarties packs, and my blood sugar levels would be fatal. So why, then, when I enjoy a sugary treat, do I not go into severe hyperglycemia?

The answer is insulin. Our bodies release insulin right before and during eating, and that insulin tells our bodies to start taking glucose out of the blood, thus lowering our blood glucose levels. It does this by both promoting uptake of glucose by cells and the storage of glucose within our cells. Without insulin, we would all go into hyperglycemic shock and die from something as common as a hamburger.

What is Insulin?

Insulin is a relatively small peptide hormone produced by β-cells in the pancreas. It’s main job is to signal the liver, muscle and fat tissues to take up glucose from the blood and store it as glycogen. As the glucose level in the blood drops to normal, insulin release slows or stops. If it drops too low, an antagonistic hormone, called glucagon, is released which does the opposite of insulin, stimulating cells to break down glycogen and release glucose.

But insulin does much more than just control blood glucose levels. Its effects depend on the cell type that receives its signal. Fat cells, for example, don’t take up or store glucose. Instead, they respond to insulin by taking the fats that enter the blood stream and turning them into fatty acids, which they store in large vacuoles. Thus insulin promotes the uptake and storage of fat in our adipose tissues. While insulin levels are high, our bodies don’t digest or use fats for fuel. Instead, we rely on the glucose in our blood and tissues. This is key to keep in mind when trying to lose weight – you body simply won’t break down and use your fat reserves with insulin around.

Furthermore, insulin stimulates the body to absorb most amino acids. However, it doesn’t lead to intake of tryptophan by cells. This creates an effective rise in tryptophan concentration in the blood, allowing it to pass through the blood brain barrier. In the brain, tryptophan is converted to serotonin, a neurotransmitter whose primary purpose, in this case, is to reduce appetite. But serotonin has a lot of other effects, as those of you who have read the previous Understanding Our Bodies on Serotonin know well. In general, increased serotonin leads to a feeling of happiness and calm, which is why we get such satisfaction when we eat. Thus insulin is important not just when it comes to dealing with fats and sugars but in regulating our emotions, too!

It turns out insulin in the brain has a lot of functions, very few of which we understand well. Mice that lack insulin and leptin receptors in their brains, however, exhibit insulin resistance that is characteristic of diabetes. Strangely, though, they have a lot of reproductive deficiencies, too – the females have poor fertility, high testosterone levels and deformed ovaries, for example. Why insulin has these effects on reproduction is unknown, but it just goes to show that insulin does a lot more than regulate blood sugar levels, and is far more important in our bodies than we once thought.

Regulating Insulin

While insulin levels are mostly regulated by the amount of glucose in our blood, other things can stimulate its release. Other molecules from digestion, like certain amino acids, proteins and lipids, can similarly stimulate insulin release. But most incredibly, our bodies begin releasing insulin before we even take a single bite of food. When we think about, smell, or slightly taste foods, our brains trigger what is called Cephalic Phase Insulin Release. A food’s color, appearance, flavor, aroma, and texture can all impact how our brains respond to the idea of eating it. The goal is to prepare the body for what the brain thinks will be a sudden flood of glucose. The sweeter and sugarier the brain thinks the meal will be, the more insulin it stimulates the pancreas to release before the food even enters the mouth.

Once we start to eat, our bodies ramp up insulin secretion, in what is often called first phase insulin release. Insulin that was kept in storage while our blood glucose levels were normal is released all at once, leading to a dramatic increase in insulin levels. The amount of insulin secreted in the first phase response to a meal is determined by the amount of glucose encountered in the previous meal – the more you needed last time, the more is released in this first phase. In a healthy person, this first phase response peaks a few minutes after you’ve started your a meal.

The β-cells then take a quick pause. If the first pulse was enough, then they slowly take up the insulin they released, and store it for the next meal. If the blood glucose levels stay high, though, the β-cells begin producing and releasing insulin in pulses every ten to twenty minutes. They continue this until the body’s blood glucose gets back to normal levels. The blood sugar rise caused by the meal peaks about half an hour after eating, and this, in turn, leads to a decrease in insulin production and release.

There are other regulators of release of insulin, too. Stress hormones like noradrenaline inhibit insulin release. This makes sense when you think about it evolutionarily. The purpose of stress hormones is to prepare our bodies for a sudden need to act. If we see a tiger, for example, our stress hormones spike so we can be prepared to fight if it attacks or run like hell to get away. Either way, we’ll need extra energy on hand to deal with the stressful situation, so stress hormones stop insulin from being released to ensure that a little extra glucose is in the bloodstream and able to reach whatever body parts need it most.

Not all insulin is produced in the pancreas, though. The brain also produces its own supply of insulin. The brain is a complex organ and needs lots of fuel to run properly. Insulin in the brain enhances learning and memory. Meanwhile, reduced levels of insulin and its related proteins are linked to Alzheimer’s disease and other degenerative disorders.

Insulin and Disease

Insulin is at the heart of many diseases. As I just explained, insulin in the brain is particularly key, and can lead to neurological disorders. But too much or too little insulin in the body is a big problem, too. There is a special name for the series of diseases caused by impaired insulin signaling in the body. You might have heard of it: Diabetes Mellitus.

Diabetes occurs when the body does not have the insulin signaling it should. There are two major types: type 1 and type 2. People with type 1 diabetes tend to realize their condition early in life, and must deal with it throughout their lifetime, while those with type 2 tend to develop symptoms later on. What’s the difference? While both conditions involve problems with the insulin pathway, type 1 diabetes is caused by a lack of insulin, while type 2 is caused by chronically high levels. People with type 1 diabetes have innately low levels of insulin due to genetic mutations. Without the ability to produce enough of this vital hormone, they usually have consistently high blood glucose levels. While this is a problem, there are many forms of treatment, including insulin injections. By carefully controlling their sugar intake and taking insulin when they need it, people with type 1 diabetes can regulate their blood glucose levels to being almost normal.

Type 2 diabetes is different. Type 2 diabetes results from the body having high insulin levels for too long. Insulin is meant to be a fast acting hormone – you release it when glucose levels are high, so that they drop. Then the signal stops. If you constantly eat too much or have a very sugary diet, you can end up with high insulin levels all the time. This leads to the body becoming desensitized to insulin. It’s kind of like trying to listen to a radio with static. If you only get a little static every once in a while, you can hear the song fine, and understand what the artist is saying. But start having high static all the time and you can’t tell what song is playing anymore. Your body, in effect, can’t tell what signal it’s supposed to be getting, and instead stops listening all together. Type 2 diabetes is that much more dangerous because the body will rarely respond to insulin treatment, meaning that drastic diet changes and exercise are the only ways to fight back.

Sadly, more than 90% of diabetes cases are type 2. Prevalence rates of type 2 diabetes doubled between 1990 and 2005, causing the CDC to declare it an epidemic.

Insulin is also a key player in Metabolic Syndrome. Metabolic syndrome, often called prediabetes, is poorly characterized, and even more poorly understood. Symptoms include elevated blood pressure, high blood cholesterol, and increased waist circumference. The main cause appears to be decreased response to insulin in certain tissues, specifically muscle and fat. The thing is, we’re not sure if it’s treatable or an irreversible first step in Type 2 diabetes. Often, people with metabolic syndrome are overweight, and at higher risk for other, even more life threatening conditions like heart disease. While some drugs can be prescribed to treat the symptoms like high blood pressure, the only long-term solution is to lower chronic blood glucose levels and restore insulin sensitivity, if, indeed, it can be restored at that point.

Nutrition and Insulin: Glycemic Indexes, Glycemic Loads and Beyond

Everyone should think about insulin and blood glucose levels, not just people with diabetes or metabolic syndrome. What we eat, how much of it, and when can impact our insulin release, which in turn can have a big impact on our bodies and how we feel.

 

The major dietary players in insulin regulation are carbohydrates. While fats, proteins and everything else can increase blood glucose levels, carbohydrates do it much faster for two simple reasons: firstly, they’re one of the first things we break down in digestion. There are enzymes in our saliva that begin carbohydrate breakdown before the foods even reach our stomachs! But more importantly, carbohydrates lead to immediate rises in blood glucose because they contain glucose. Other molecules must first be converted to glucose, but carbohydrates, which include sugars, just need to be hacked into pieces by our digestive enzymes. Different carbohydrates contain different amounts of the monosaccharides, like glucose or fructose. Thus they each have different impacts on immediate rises in blood glucose levels.

This difference in effect on blood sugar level is the basis of the Glycemic Index, or GI. The glycemic index rates foods based on how much of an immediate impact they have on blood glucose per 50 grams of carbohydrate. If you picture the rise in blood glucose levels in response to a food on a graph over time, the glycemic index is a number that is related directly the area under a two-hour curve. The higher the spike in blood glucose levels, the larger the area under the curve is, and thus the higher the glycemic index, which is somewhere on a scale of 1 (low) to 100 (high). Most foods that have a low GI induce lower spikes in insulin, but not all of them. There is another index, called the Insulin Index, that looks directly at rises in insulin levels. While the glucose and insulin scores of most foods are related, high-protein foods and baked goods that are rich in fat and refined carbohydrates usually elicit much higher insulin responses than their glycemic index values would suggest.

Research into the glycemic index have found strong support of the idea that low GI foods are better for us. People who eat less high GI foods have lower risks of developing both type 2 diabetes and heart disease. It’s uncertain if this is due to overall lower blood sugar levels or reduced glycemic “spikes.” When glucose levels increase dramatically, our bodies ramp up the release of insulin and the processing of glucose from the blood, including ATP generation. While ATP is great, the process by which we make it – oxidative phosphorylation – has side effects. Mainly, the faster it’s churning, the more likely the machinery is to leak reactive oxygen species (ROS). These oxygen radicals are highly reactive and tend to transform whatever they come in contact with, which can cause damage to proteins, membranes, or even our DNA. By eating foods that increase glucose levels more slowly, we limit ROS bursts that can damage our cells.

However, the glycemic index isn’t perfect. Glycemic indices aren’t the whole story since they are based on a per-carbohydrate basis. Two foods that have the same GI can have dramatically different effects on blood glucose per serving if one has significantly higher carbohydrate content than the other. The affect a serving of food has on blood glucose is referred instead to its Glycemic Load. Glycemic load is calculated by multiplying the weight (in grams) of carboydrate in a serving by the food’s overall GI and divided by 100. A GL of 10 or less is considered low, while 20 or more is considered high. Let’s say you want to eat a baguette, for example. Both whole gain and French baguettes have similar GIs (roughly 73). But there’s a lot less carbohydrates per serving in the whole gain loaf, and thus its GL is only 9 while the GL of the french baguette is 27!

The GI or GL of a food isn’t the only thing you should consider when it comes to insulin and your diet. When you eat matters a lot, too. Our bodies react to the same foods differently at different times of day. Morning is a special time for your body because you’ve just spent a while in a comatose state. The changes your body undergoes while you sleep can have a dramatic impact on how it responds to food. Insulin levels tend to be low in the early morning, for example, because your body releases stress hormones just before you wake up. Once you’re awake, though, your body ramps up insulin secretion to metabolize the high glucose levels and give your cells a little fuel to start the day with.

These alterations have a big impact on how our diets affect us. When different foods were tested for their GI values at different times of the day, for example, researchers found that the same food eaten for lunch instead of breakfast induced a lower glucose response. This is why it may be particularly important to eat a protein-rich breakfast, like eggs, instead of high glycemic foods like white bread toast. Time of day has been found to have a larger effect on insulin responses in women than in men, though no one understands why. Furthermore, studies have shown that the quality of sleep you get affects how strongly your body reacts to food. A restless night can lead to higher glucose responses and larger spikes in insulin in response to food in the morning. So getting a good night’s sleep is also important in preventing the kinds of spikes which may be a major factor in type 2 diabetes.

Also, foods can interact with each other to lower or raise the GI values of a meal. For example, foods that contain fiber, protein, or fat will generally reduce the GI of the meal as a whole. Recent studies have even shown that having a small volume of alcohol (one drink) prior to a meal reduces the GI of the meal by 16-37% – which, as far as I’m concerned, is fantastic news. Furthermore, many cultures eat high GI foods like potatoes or rices but have low occurrences of diabetes and obesity. The truth is we have yet to tease out all the factors that lead to these conditions, and the GI level of our diets is likely only one of many related factors.

The Even Bigger Picture

Clearly, what we eat, with what and when matters a lot when it comes to insulin levels. This is important in keeping healthy and reducing the risk of metabolic syndrome and type 2 diabetes. But insulin affects so many other things in our bodies, from amino acid uptake to fat storage. We need to consider insulin whether we’re worried about type 2 diabetes or not!

Thinking about how our diet affects insulin is especially key when trying to lose weight or maintain a healthy weight. Insulin actually triggers the storage of fats in adipose tissues, so sustained high levels of insulin promote weight gain! Furthermore, recall that our bodies don’t break down fat while insulin is circulating. This means that if we eat foods with high GIs that produce sustained insulin levels, we’re shooting ourselves in the foot, even if we eat less calories overall.

Understanding how our bodies regulate insulin release also explains why certain foods are worse for us than we’d expect. Sugary drinks are particularly bad for us, for example, even when we take into account their calorie and sugar content. This is because our brains don’t judge their sugar content well in advance. Thousands of years of evolution led our brains to believe that drinks, overall, were low-cal things that mostly contain water. Our brains aren’t wired to think that fluids contain a lot of sugar. Thus when we look at a soda or even begin to sip one, we don’t have the same level of cephalic phase insulin release or first phase insulin release that we would for a solid treat. The end result of this is that our bodies are unprepared for the sudden sugar rush, and have to instead release a massive amount of insulin all at once to deal with what it considers an inexplicable rise in blood glucose.

High spikes in insulin lead to dramatic drops in blood glucose, which can cause your body to feel hungry sooner. Eating low GI and GL foods can help you lose weight by making you feeling fuller longer. Low GI foods don’t cause dramatic drops in glucose levels, thus you tend eat less throughout the day. It’s thought that this effect, on top of the high-sensitivity of our bodies to high GI foods in the AM, is why eating eggs, a low GI food, instead of cereal or toast in the morning has been found to reduce overall food intake for the day by as much as 18%. You can create lower spikes in insulin not only by avoiding sugary drinks and eating lower GL foods but also by eating smaller meals. This is because the amount of first phase insulin release is dependent on the amount of insulin needed for the previous meal. The bigger meals are, the larger the spike at the beginning of every meal, and the bigger the drop in glucose afterward.

But you shouldn’t just cut out everything that leads to insulin release! Insulin is important, and too little is just as bad as too much. Even small drops in daily insulin levels can affect us negatively. For example, dieters often experience depression around 2 weeks after they begin cutting high-glycemic foods like carbohydrates out of their diet. Why? Because they have much lower levels of insulin than they did before. Decreased insulin means decreased amino acid uptake, and because the level of other amino acids affects how well tryptophan crosses the blood brain barrier, decreased insulin means less serotonin which leads to, in layman’s terms, feeling like crap. While you should monitor the GI of your meals to reduce insulin spikes, you shouldn’t go for rock bottom either. At least you shouldn’t if you want to be happy about it!

Previous posts in the Understanding Our Bodies series:

• Leptin: The Fullness Hormone
• Serotonin: The Connection Between Food and Mood
• Amino Acids are Important!
• Dopamine and It’s Rewards
• The Role of Antioxidants
• Fiber!

Citations:

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Hill, J., Elias, C., Fukuda, M., Williams, K., Berglund, E., Holland, W., Cho, Y., Chuang, J., Xu, Y., & Choi, M. (2010). Direct Insulin and Leptin Action on Pro-opiomelanocortin Neurons Is Required for Normal Glucose Homeostasis and Fertility Cell Metabolism, 11 (4), 286-297 DOI: 10.1016/j.cmet.2010.03.002

Spiegel K, Knutson K, Leproult R, Tasali E, & Van Cauter E (2005). Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes. Journal of applied physiology (Bethesda, Md. : 1985), 99 (5), 2008-19 PMID: 16227462

Brand-Miller JC, Fatema K, Middlemiss C, Bare M, Liu V, Atkinson F, & Petocz P (2007). Effect of alcoholic beverages on postprandial glycemia and insulinemia in lean, young, healthy adults. The American journal of clinical nutrition, 85 (6), 1545-51 PMID: 17556691

Ratliff J, Leite JO, de Ogburn R, Puglisi MJ, VanHeest J, & Fernandez ML (2010). Consuming eggs for breakfast influences plasma glucose and ghrelin, while reducing energy intake during the next 24 hours in adult men. Nutrition research (New York, N.Y.), 30 (2), 96-103 PMID: 20226994