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| Glucose Control | |
The last few articles explained that the volume of the intracellular fluid (ICF) must be controlled for cell survival and so must its chemical content, which is totally different than the extracellular fluid (ECF). Also, for survival, to maintain enough blood volume, a function of the extracellular space, there must be the right amount of albumin in the blood and total body water. In addition, for proper nerve and muscle function, there must be the right amounts of sodium, potassium and calcium in the ECF vs the ICF. To perform these metabolic feats, cells use sodium-potassium and calcium pumps and the liver makes the right amount of albumin. The hypothalamus triggers the release of the right amounts of ADH, the adrenals, aldosterone, and the atria, ANP, and parathyroid glands release the right amounts of PTH to affect the kidneys and the function of the gastrointestinal system and bones. Besides needing the right information to make all of these biomolecules and organs to perform their tasks, something else is needed. In fact, cells can’t survive or function properly without it. Q. What do you think it is? A. Energy! Energy Q. But how does the cell get this energy? A. Cellular respiration. Here’s how it works. Cellular respiration is the process in the cell by which, in the presence of molecular oxygen (O2), the chemical energy in the glucose molecule is released by breaking the bonds between its atoms. In contrast to a car engine, which uses a spark and O2resulting in a semi- explosive quick release of energy from gasoline, cellular respiration uses O2 and a series of specific enzymes to release the energy from the glucose molecule in a more controlled fashion. The energy released in this way is not in an immediately useable form. About 30% of it is stored, (like a battery) in ATP (adenosine triphosphate), the energy currency of the cell, while the rest is released as heat. The various structures of the cell are then able to use the energy stored in ATP to do what they need to do for the cell to survive and function properly. Let’s take a closer look at the glucose problem. Following the Rules of MCO (Human) Life Since the body consists of atoms and molecules, it is affected by the forces of nature and the laws that govern them. As noted above, “following the rules” means, for the body to survive and function properly it must have enough energy and it gets it from cellular respiration which breaks down glucose in the presence of O2. Experience teaches that there has to be enough glucose in the blood for the body, especially the brain, to work properly. The normal blood glucose ranges from 70-90 mg/dL. If it drops below 55 mg/dL, mild symptoms such as hunger, shakiness, anxiety, sweating, fatigue, irritability and problems with concentration are experienced. If it drops below 45 mg/dL moderate symptoms like weakness, confusion, dizziness, drowsiness, blurred vision, slurred speech and impaired judgment occur. And if it drops below 30 mg/dL then severe symptoms like clumsiness and problems with coordination, seizures, loss of consciousness and coma take hold. Finally, a blood glucose below 20 mg/dL is incompatible with life because the nerve cells are no longer able to function at all and the brainstem dies. Not having enough glucose in the blood can be life-threatening but so can having too much, like over 1,000 mg/dL. High blood glucose causes high amounts of glucose in the fluid filtered within the kidney tubules which overwhelms their ability to reabsorb all of it. This makes the body not only lose glucose through the urine, but the high glucose content of the urine, by the power of osmosis, makes the kidneys lose excessive amounts of water. Moreover, high blood glucose also makes water move out of the cells by osmosis. The combination of the cells giving up too much water to the blood and the kidneys losing too much water from the body results in severe dehydration leading to very low blood pressure, debility and even death. The Hard Problem As noted above, having a blood level of glucose within the right range is vital for life because having too much or too little glucose in the blood can cause debility and death. The gastrointestinal system is very efficient at putting glucose into the blood from what the body takes in. Within a couple of hours of any caloric intake the blood glucose quickly rises. How then does the body make sure that the level of glucose in the blood doesn’t go too high? Moreover, whether the body is at rest or very active, it is always using up glucose for its energy needs. If it hasn’t taken in any calories for several hours, then how does the body make sure that there is enough glucose in the blood to do what it needs to do while not letting it go too low? Here’s how Steve Laufmann and I explained these situations in our book Your Designed Body.
So, how does the body maintain the right blood glucose level while taking into account how much it brings in from the gastrointestinal tract and how much it uses for energy? This is a very important practical question for which the body must have an adequate answer. What type of dynamic innovation do you think would be needed to solve this hard problem? What sorts of information would be needed to manage the blood glucose level? Take a few minutes to think it through. The (Dynamic) Innovative Solution(s) The pancreas is the dynamic innovative organ that helps to manage the blood glucose level. The first thing needed to take control is a sensor that can detect what needs to be controlled. The pancreas has alpha and beta cells with glucose sensors to let them detect the blood glucose. The second thing needed to take control is something to integrate the data, decide what needs to be done, and then send out orders. When beta cells detect the rise of blood glucose above 80 mg/dL to over 100 mg/dL (like after a meal), they send out more of a hormone called insulin. And when the blood glucose drops under 100 mg/dL toward 80 mg/dL (like after being active with no oral intake for several hours) they reduce their insulin output to very low or minimal levels. Alpha cells do the opposite of what insulin does. When they detect the blood glucose dropping toward 70 mg/dL (like after being active with no oral intake for several hours) they send out more of a hormone called glucagon. And when the blood glucose rises over 70 mg/dL toward 100 mg/dL (like after a meal), they reduce their glucagon output to very low or minimal levels. The third thing needed to take control is an effector that can do something about the situation. As the blood glucose rises after a meal, the insulin sent out by the beta cells travels in the blood where it locks onto specific insulin receptors within target organs, especially the liver, and tells them to take in glucose for energy and store what is left over. In general, insulin is an anabolic hormone in that it promotes the formation of more complex molecules from simpler ones. Not only does it promote the formation of the carbohydrate storage molecule glycogen from glucose in the liver and muscles, it also tells some cells to take in amino acids to form proteins and others to take in fatty acids to form fats. In contrast, several hours after a meal, the blood glucose drops because the body has stored some of the glucose as instructed by insulin and is using it for its energy needs without having brought in new supplies. The glucagon sent out by the alpha cells in response travels in the blood where it locks onto specific glucagon receptors on target cells, mainly in the liver, and tells them to release the glucose from within glycogen and other forms of stored energy. In general, glucagon is a catabolic hormone which promotes the breakdown of more complex molecules into simpler ones. Not only does glucagon cause glucose to be released from the glycogen stores, it also tells cells to breakdown certain proteins and fats into glucose and ketones, so the brain can be use them for energy as well. Insulin and glucagon order the liver and other cells to do opposite things. Insulin signals the body that it is in the “fed state” and must take glucose out of the blood and store it in the liver and fat cells for later use. Glucagon signals the body that it is in “starvation mode” and must release glucose and other energy molecules from the liver and fat cells and place it in the blood so the brain will have enough energy. Beyond endogenous controls, clinicians sometimes modulate this insulin glucagon choreography via the incretin pathway for example with oral semaglutide (Rybelsus), a GLP-1 receptor agonist. By amplifying glucose-dependent insulin secretion, dampening inappropriate glucagon release, and slowing gastric emptying, it reinforces the “fed-state” signals when glucose is high without driving hypoglycemia in the fasted state. In this way it leverages the same physiological levers described above, but with a pharmacologic nudge that helps smooth post-meal excursions and overall glycemic balance. It is important to note that due to the breakdown by enzymes the metabolic effect of a given amount of insulin and glucagon only lasts a few minutes and the ratio of insulin and glucagon allows the body to have “moment to moment” blood glucose control. A good example of the body’s recurring design patterns is its use of insulin and glucagon to maintain control of blood glucose in what we in our book, Your Designed Body, called “The Push-Pull Principle”. Here’s what we said. See if you agree!
Real Numbers Have Real Consequences Physicians and engineers do their work within the real world where real numbers have real consequences—even death! Here is how we expressed it in Your Designed Body.
As opposed to physicians and engineers, the concept of “functional capacity” seems to be totally absent from the mindset of evolutionary biologists. That’s because their theoretical constructs always lack the objective criteria needed to verify that a given biological structure works well enough for survival—in other words its functional capacity and the control mechanisms needed to maintain it are good enough. Yet, no matter how complex the genetics leading to a sophisticated biological structure, if it can’t control and maintain the functional capacity to combat and/or use the laws and forces of nature to its advantage, the organism in which it is housed is as good as dead. The same applies to glucose. A blood glucose below 20 mg/dL is incompatible with life as is the absence of glucagon. And a blood glucose over 1,000 mg/dL is soon incompatible with life as is the absence of insulin. When it comes to human life, real numbers have real consequences! “Evolutionary “Explanations”
Questions
Onward!
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Life