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Metabolic Primer Part I

                                                                                                                                                   Researched and Composed by Joe “Yu Yevon” King

Introduction

Allow me to tell you a story of a man who lived about 2,400 years ago in Athens, Greece. This man had an undying desire for knowledge. He had an inquisitive mind and always answered a question with another question. As a teenager, he would walk the streets following other intellectual and abstract thinkers who appealed to him. One of these thinkers was a man named Plato. Plato, intrigued by the young man’s deep philosophical incite, asked him to attend his university of philosophical thought. The young man did and went on to become Plato’s best student - and one of the worlds greatest thinkers.

This man was Aristotle. After spending years at Plato’s university, Aristotle went on to be the personal tutor of Alexander the Great. At the age of fifty, he started his own school of philosophy. He lived only ten more years, but amazingly in his sixty years of life, he produced nearly a thousand books and pamphlets. Unfortunately, very few remain.

Of course, we know that the author of Ecclesiastes, Solomon, speaks the truth when he says, “Making many books, there is no end; and much study is a weariness of the flesh” (24). Aristotle knew this, too, and so we are told that when he sat writing, he held a metal ball in one hand while he wrote with the other. When he grew tired and began to fall asleep, the ball would drop to the floor and loudly awaken him back to philosophy.

The founder of logical theory, Aristotle believed that the greatest human endeavor is the use of reason in theoretical activity. One of his best known ideas was his conception of “The Golden Mean” - “avoid extremes,” the council of moderation in all things.

Side note: His greatest student - Alexander the Great - obviously never got this point.

Today you hear athletes and scientists alike promote  “everything in moderation.” What does that mean exactly? Simply put, too much of a good thing is bad. Conversely, too little of a good thing is also bad. We must find the middle ground - the equilibrium point.

The debate over carbohydrate consumption was long-standing. But with new and solid scientific evidence surfacing every month, it is clear that the debate is over. Severe carbohydrate restriction is not only counter-productive, but dangerous as well.

In this article, I outline the metabolism of carbohydrates. Many of the topics I have already touched on, so you may want to refer back to my Endocrine Insanity series throughout the preceding article.

Enter Metabolic Primer!

CARBOHYDRATES

Our bodies use carbohydrates (CHO) as fuel to obtain energy (ATP and heat). Dietary carbohydrates consist of starches (found in bread, rice, pasta, and potatoes), fruits, beans, and milk.

Carbohydrates may be simple sugars (six-carbon monosaccharides, principally glucose, galactose and fructose), oligosaccharides (chains of two to ten simple sugars), or polysaccharides (larger polymers of glucose or other simple sugars).

Polysaccharides occur in starches; disaccharides are found in milk (lactose) and table sugar (sucrose). The monosaccharide fructose is the sugar found in fruits.

It is important to note that only simple sugars can be absorbed. All carbohydrates are digested by intestinal enzymes into only three simple sugars: glucose, galactose, and fructose. These are absorbed across the intestinal mucosa and transported via the portal vein to the liver.                      

Skeletal muscle contains the largest depot of stored carbohydrates in the body in the form of muscle glycogen. Glycogen granules appear as bread-like structures localized to specific subcellular locales. Each glycogen granule is a functional unit, not only containing carbohydrates, but also enzymes and other proteins needed for its metabolism. These proteins are not static, but rather associate and dissociate depending on the carbohydrate balance in the muscle.

Liver and its role in carbohydrate physiology

Simple sugars are transported into liver cells. Here, galactose and fructose are enzymatically converted into glucose. Glucose is the only sugar normally found in the blood. Glucose enters the bloodstream directly during the absorptive phase, but during other times, the liver is the only source of blood glucose. The glucose pool in the liver is easily exchanged with that in the blood. The tissues obtain the glucose they need from the blood glucose pool.

When blood glucose levels are low, the liver releases glucose into the blood to maintain equilibrium. Conversely, when the blood glucose levels are high, the liver cells can take up and store glucose. This process is known as storage and conversion. The liver acts as a glucostat - helping to maintain the blood sugar within normal levels.

After a high carbohydrate meal, blood sugar rises resulting in increased glucose uptake by the liver cells. The excess glucose within the liver cells promote the incorporation of glucose into glycogen - a polymer of glucose - via a process called glycogenesis.

Glucose residues in glycogen are bound together along branched chains, forming a tree-like structure, the glycogen tree.

Excess glycogen can enter into the cytoplasm to form glycogen granules, found abundantly in liver and muscle cells. When the pool of free glucose in the liver cells diminishes, glycogen is partially broken down, by a process called glycogenolysis, to release free glucose.

The livers ability to form glycogen is limited. As a result, the extra glucose entering the liver in the absorptive and postabsorptive phase is converted into amino acids and proteins as well as to fats (triacylglycerols) with the formation of glycerol and fatty acids. The liver is efficient at making fat.                 

Two metabolically distinct forms of glycogen, pro- and marcoglycogen have been identified that vary in their carbohydrate complement per molecule and have different sensitivities to glycogen synthesis and degradation (67).

I will delve deeper into glycogen in a later issue.

Gluconeogenesis

To make glucose, the liver breaks proteins into amino acids. Some of these amino acids undergo deamination to form pyruvic acid, which can, in turn, be converted into glucose by a process known as reverse glycolysis.

The process of gluconeogenesis is carried out by special liver enzymes and is a major source of the new and endogenous glucose for the liver and blood - especially during starvation and fasting.

Another source for the formation of new glucose molecules is the glycerol liberated by the breakdown of triglycerides (lipolysis) in the liver and fat cells. Glycerol molecules can be recombined to form glucose through the reverse steps of glycolysis. The liver, however, is unable to convert fatty acids to glucose, as it lacks the necessary enzymes. Lactic acid is another source of endogenous glucose, being converted to pyruvate and then to glucose via glycolysis.

As I stated in Endocrine Insanity Part III, some tissues, such as the brain, rely principally on glucose for their energy needs. Depriving the brain of glucose leads to serious irreversible damage, particularly in the brain cortex tissue. Other organs, such as the heart and skeletal muscle, prefer to use glucose for energy but are also able to use alternative fuel sources, such as fatty acids.

How muscle utilizes glucose for energy

In stimulated skeletal muscle cells, glucose is taken up rapidly from the blood and converted into glucose-6-phosphate (G-6-P). G-6-P is then converted to pyruvate by the enzymes of glycolysis (aerobic glycolysis) and, when oxygen is present, to CO2 and H2O (water) by the enzymes of the Krebs cycle in the mitochondria of the skeletal muscle cells.

The glycolytic breakdown of glucose to pyruvate yields a small amount of ATP (2 ATP/glucose). Mitochondrial oxidation of pyruvate to CO2 and H2O yields much more ATP (38 ATP/glucose). The latter is what the muscles use for their contraction.

When the oxygen levels in the muscle tissue is not sufficient for the above to take place, the muscle fiber uses pyruvate to form lactic acid (lactate). This process is called anaerobic glycolysis, which yields two more ATP molecules, although it is still far less than what is obtained via the Kreb cycle in the mitochondria. If muscle activity (contraction) continues, lactic acid builds up and leaks into the blood stream. Here, the lactic acid is absorbed by the liver where lactate is then converted into pyruvate and then to glucose. The glucose is then recycled and used again by the muscle tissues. This cycle is known as the Cori cycle.

When the muscle is at rest, the glucose taken up by the muscle cells is immediately converted into G-6-P. Because ATP is not being utilized when the muscle is at rest, the G-6-P is used to form glycogen, thus storing the available glucose.

During muscle activity, this glycogen is converted back to G-6-P, which is used directly for glycolysis. G-6-P cannot be converted to free glucose because it is missing the appropriate enzyme. Therefore muscle glycogen can only act locally - within the muscle cell.       

Carbohydrate Supplementation and Exercise

The first introduction of a high-protein, low-CHO diet can be traced to Stymphalos, a 2-time Olympic victor. Stymphalos was a long-distance runner who claimed that his meat-based diet was the basis for his high level of performance (71). Milo of Croton, a renowned Greek wrestler and a 5-time Olympic champion who competed from 536 to 520 BC, was reported to have consumed 9 kg of meat each day. Many modern athletes are again touting the accolades of high-protein, low-CHO diets. In contrast to this recent explosion of support for low-CHO diets, modern sport nutritionists and sport scientists currently recommend diets rich in CHOs (9). All of these dietary regimes have one goal, the improvement of athletic performance. With this increased interest in improving sports performance through nutritional interventions, a wide variety of diets have been proposed for a magnitude of reasons. These diets range from those that are rich in CHOs to those that require a sparse consumption of CHOs. At present there is some debate about the efficacy of low-CHO diets and sports performance, especially in the anecdotal reports in the popular press.

The majority of the energy utilized for high-intensity, short-duration anaerobic exercises such as resistance training have been thought to be derived from muscular stores of phosphagens (ATP-PC system) (49). However, recent research suggests that resistance training can stimulate significant amounts of glycogenolysis (29, 58, 76). This research indicates that there can be a 13–40% decrease in muscle glycogen content in response to various resistance-training protocols. The amount of total work performed and the volume of training are related to the degree of muscle glycogen loss.

When resistance training–induced muscle glycogenolysis is examined closely, there appears to be a fiber type–dependant depletion pattern. Several researchers have clearly shown that high-intensity resistance training can preferentially deplete type II fibers. Robergs et al. (61) reported that type II fibers exhibited significantly greater glycogen loss than did type I fibers in response to 6 sets of 6 repetitions performed at 35% and 70% of 1RM. Additionally, Tesch et al. (76) reported that type IIa fibers are depleted by 40, 40, and 70% in response to concentric leg extensions performed at 30, 45, and 65%, respectively. The 65% trial also elicited a 30% decrease in glycogen content of type IIab + IIb fibers, whereas the 30 and 45% trials stimulated no change in glycogen in these fibers. Therefore, an acute bout of moderate- to high-intensity resistance training preferentially depletes type II fibers of female and male athletes. This phenomenon is not totally unexpected because type II fibers have higher glycolytic enzyme activities than those expressed in type I fibers. Because resistance training and other high-intensity anaerobic exercises tend to rely upon glycolysis to supply energy, the preferential glycogen depletion of type II fibers during these exercises may compromise training intensity and ultimately decrease competition performance.

Theoretically, these effects may be magnified when athletes are performing multiple training sessions consisting of high-intensity exercise during the same training day. If, for example, 2 high-intensity resistance training sessions were undertaken during a training day, a larger decrease in muscle glycogen stores would be expected when compared with those resulting from a single training session. If postexercise CHO ingestion were inadequate or delayed by as little as 2 hours, a significant decrease in muscle glycogen storage would occur (37). Impairments in the resynthesis of muscle glycogen stores would then result in a decreased availability of glycogen, which could result in a decreased ability to maintain the workout intensity or volume of training during the second workout session on that training day.

Diets that are low in CHO and are coupled with intense training protocols will result in a significant suppression of muscle glycogen content (25, 42, 69) and possibly impaired high-intensity exercise performance (46, 51, 59). Suppressed levels of muscle glycogen have been linked to decreases in isokinetic force production (38), isometric strength, and time to fatigue and increases in exercise-induced muscle weakness. The suppressed glycogen levels and inability to perform maximal exercise with a low-CHO diet are most likely results of impaired glycogen synthesis, which occurs because fat and many amino acids do not contribute significantly to gluconeogenesis or glycogen synthesis (7). These findings indicate that a low-CHO diet is not advisable for athletes who perform high-intensity anaerobic exercise, such as resistance training.

Scientific evidence suggests that high-intensity anaerobic exercise, including resistance exercise performance, is affected by the availability of muscle glycogen stores. The amount of glycogen utilized during this type of exercise appears to be related to the total amount of work accomplished during the exercise bout. The daily maintenance of glycogen stores may play a crucial role in maximizing resistance exercise performance. Low levels of muscle glycogen have been linked to impairments in isokinetic and isometric exercise performance. Because of the strong relationship between the amount of dietary CHO and muscle glycogen synthesis, diets that are low in CHOs may result in a decrease in muscle glycogen stores and thus impaired exercise performance. Anaerobic performance may be further compromised by a preferential utilization of type II muscle fibers.  

Countless studies have shown the effectiveness of pre- and post-workout carbohydrate consumption. A recent study conducted by Dr Terry Graham concluded that carbohydrate ingestion prior to and during prolonged exercise can increase endurance as well as promote muscle recovery and growth (27). Let’s investigate further:

Dr Michael Leveret et al. conducted a study testing the effects of a low carbohydrate diet on strength performance (45).

The study investigated the effect of a carbohydrate restriction program on performance in a bout of isoinertial and isokinetic strength exercise. One female and five male subjects performed isoinertial and isokinetic strength exercise under control conditions (no experimental intervention) and after a 2-day carbohydrate restriction program. The carbohydrate restriction program consisted of 60 minutes of cycling at 75% of peak cycle ergometer oxygen consumption (PVO₂), followed by four 1-minute bouts at 100% of PVO₂, followed by 2 days of reduced carbohydrate intake.          

Isoinertial strength exercise was three sets of squats with a load of 80% of one repetition maximum. Isokinetic strength exercise was five repetitions of leg extensions performed at five different contractile speeds.

What did they find?

The carbohydrate restriction program caused a significant reduction in the number of squat repetitions performed. Torque at 0.52 rad from full extension (T30) was not significantly altered by carbohydrate restriction. Plasma lactate concentration postexercise was significantly lower after carbohydrate restriction.

Hence they concluded:

Isometric strength has been shown to be impaired by reducing muscle glycogen content. However, high repetition isokinetic activity does not appear to be affected by a reduction in muscle glycogen stores.

The results of this study have shown that a program of carbohydrate restriction, involving both an exercise and a dietary intervention, impaired isoinertial squat performance but not isokinetic leg extension performance. It is tempting to suggest that the carbohydrate restriction program used in this study caused a reduction in muscle glycogen levels and that reduced muscle glycogen was responsible for causing impaired performance during isoinertial strength exercise.

Craig et al. (15) observed that strength development was compromised during concurrent strength and endurance training when subjects performed all strength training sessions immediately after endurance training. These authors speculated that fatigue from a previous endurance training session may have compromised the quality of subsequent strength training and therefore did not allow for optimal strength development. Jacobs (38) has also suggested that the time required to give the body sufficient recovery between training sessions may be the limiting factor when attempting to induce simultaneous adaptations to strength and endurance training.

It is clear that we need to further investigate fatigue mechanisms, often associated with endurance exercise, that may cause reductions in strength performance. A candidate mechanism for acute fatigue is muscle glycogen depletion. Muscle glycogen is an important energy substrate during resistance training activity (48, 75). Strength performance is also enhanced by carbohydrate supplementation during exercise (44). Based on the results of these studies, it is clear that reduced muscle glycogen would impair strength performance.

Indeed, muscle glycogen depletion has been shown to reduce isometric strength performance (36). However, Symons and Jacobs (73) have shown that isokinetic strength is unaffected when muscle glycogen stores are reduced. Grisdale et al. (28) have shown that isometric strength performance remained decreased 24 hours after endurance exercise, regardless of whether muscle glycogen levels were repleted or remained depleted. However, low muscle glycogen appears to accentuate exercise-induced muscle weakness (81).

We do know that absolute energy production during brief (6-10 seconds) maximal exercise is predominantly provided by the breakdown of creatine phosphate (using the ATP-PC energy system), with energy production from anaerobic glycolysis being less important during this time interval (4). However, anaerobic glycolysis is the major energy source during high intensity exercise lasting 30 seconds (52). The metabolism of muscle glycogen for energy production would be much greater during the isoinertial strength activity than during the isokinetic strength exercise. Tesch (75) reported a 26% reduction in muscle glycogen levels after isoinertial resistance training activity.

Similarly, MacDougal et al. (48) also demonstrated that muscle glycogen is reduced by 25% after three sets of bicep curls to failure. It was suggested earlier that the carbohydrate restriction program was likely to have caused a reduction in muscle glycogen levels. If this was the case, subjects would not have had as much substrate available for anaerobic glycolysis during the experimental condition and this may have caused the reduction in number of squat lifts. The significant reduction in postexercise blood lactate also suggests that the activity of anaerobic glycolysis was reduced during strength exercise performed in the experimental condition. However, it is possible that some other fatigue mechanism caused the reduction in the number of squat repetitions and the reduction in anaerobic glycolysis was a consequence of the reduced amount of work performed in the experimental condition.

Clearly there is need to study the effects of pre-, mid-, and post-workout carbohydrate ingestion as to optimize muscle glycogen levels.

Performance of moderate - to high-intensity exercise lasting 35-40 min is improved by consuming a moderately high GI carbohydrate, low fat, medium protein meal 3-hr before exercise compared to a similar meal consumed 6-hr prior to exercise. Thus, athletes should not skip meals before competition or training sessions (18, 47, 72).

Gregory Haff et al. studied the effects on athletic performance with carbohydrate supplementation (30).

The effects of carbohydrate (CHO) supplementation on multiple sets of resistance training exercise during the second training session on a given training day were examined with 6 resistance-trained men (mean ± SEM; age: 24.3 ± 2.1 years; height: 176.9 ± 1.6 cm; body mass: 82.6 ± 2.8 kg). The subjects participated in a randomized, counterbalanced, double-blind protocol with testing days separated by at least 1 week. A CHO supplement consisting of 0.3 g/kg body mass¹ or placebo (P) was ingested during the morning training session, 4 hours of recovery, and the sets of squats performed to exhaustion (STE).

The STE consisted of sets of 10 repetitions of squats performed at 55% of 1 repetition maximum, with a 3-minute rest between sets, performed to muscular failure. Performance measured in number of sets (CHO: 18.7 ± 4.8; P: 11.3 ± 2.7), repetitions (CHO: 198.7 ± 46.8; P: 131.0 ± 27.2), and duration (CHO: 77.7 ± 19.4 minutes; P: 46.1 ± 8.9 minutes) were statistically different between the CHO and P trials. The results suggest that CHO supplementation enhances the performance of multiple STEs during the second workout on a given day.

The above is clear evidence that carbohydrate supplementation before a resistance workout enhances the performance of a second workout performed later that day. This is important for athletes who train more than once a day.

What about aerobic workouts though?

The effects of carbohydrate (CHO) supplementation on aerobic performance are well known (6, 11, 13, 20, 32, 55, 56, 66, 78). This line of research has indicated that the ingestion of CHO before and during endurance activities can prolong exercise duration (14, 21, 80) and increase work output (10, 33, 54). Improvements in endurance performance derived from CHO supplementation are thought to occur in response to elevated blood glucose (BG) levels. Improvements in performance may occur because of possible muscle glycogen sparing or BG becoming a predominant fuel source as glycogen becomes depleted.

Typically, weight-training exercises are associated with significant decreases in muscle glycogen.  Investigations demonstrate that muscle glycogen is an important fuel source during weight-training activities. When muscle glycogen becomes limited, the ingestion of a CHO may improve weight training performance.

Lambert et al. (44) suggested the ingestion of a CHO supplement enhances endurance performance during multiple sets of resistance exercise. As a response to CHO supplementation, blood glucose and lactate levels are increased. The increase in the available blood glucose found with CHO supplementation increases glycolysis, thus elevating lactate levels. Glycogen resynthesis after exercise can be increased by the elevation of blood glucose levels. Glycogen resynthesis also may occur during rest intervals between multiple sets of resistance training exercise. Thus, the utilization of CHO supplementation during exercise and recovery may enhance the endurance capabilities of an athlete in the second workout on a given training day.

Typically, elevated BG levels are expected in response to the ingestion of a CHO supplement during a weight-training bout (41). It is now clear to researchers that athletes who use supplemental CHO during and after the first training session on a given day have a performance advantage during the second training session when compared with athletes who are not using supplemental CHO. This ability to increase performance (41) and possibly increase glycogen resynthesis.

Ingesting carbohydrate beverages during prolonged, continuous heavy exercise results in smaller changes in the plasma concentrations of several cytokines and attenuates a decline in neutrophil function. In contrast, ingesting CHO during prolonged intermittent exercise appears to have negligible influence on these responses, probably due to the overall moderate intensity of these intermittent exercise protocols (3).

Glucose and fatty acids are the main energy sources for oxidative metabolism in endurance exercise (70). Increasing fatty acid availability attenuates carbohydrate oxidation during exercise, mainly via sparing intramuscular glycogen. Glucose directly determines the rate of fat oxidation by controlling fatty acid transport into the mitochondria. The intracellular availability of glucose, rather than fatty acids, regulates substrate interaction during exercise.

It is based on these studies that I recommend supplementation of carbohydrates during and after a high volume resistance training workout earlier in the day when a second workout will be performed later that same day.

Several investigators have shown that the residual effects of exercise can enhance glucose uptake for up to 18–24 hours following a single bout of exercise and can reduce the insulin response to a glucose load. It has been shown that anaerobic forms of exercise, such as resistance training, can produce these effects (17, 22, 53). In one study by Craig et al. (17) it was demonstrated that 12 weeks of resistance training could reduce the postexercise insulin response to a glucose load in untrained young (mean age, 23 ± 1 year) and elderly (mean age, 63 ± 1 year) subjects. These changes were well correlated to an increase in the subjects' lean body mass and raised the possibility that the enhanced muscle mass these subjects experienced was responsible for the improvement.

Of the studies that have been conducted, the main focus has been on protein synthesis (64) and anabolic hormone responses to resistance exercise (RE) (16, 43). A recent study by Roy et al. (64) indicates that carbohydrate supplementation (1 g/kg) immediately following RE attenuates postexercise myofibrillar protein breakdown. Their conclusions were based on the significant reduction in the excretion of 3-methylhistidine and urea they observed in subjects who received CHO 1 hour after exercise. In another study (8), the immediate postexercise insulin and growth hormone response of various supplements was examined. The results indicate that feeding subjects isocaloric supplements of CHO or CHO plus protein immediately following exercise has a stronger stimulatory effect on these hormones that diets containing only protein. 

The immediate postexercise rise in C-peptide levels and the exaggerated insulin response to a glucose load observed after the RE trial but not the TR trial suggest that RE has a stimulatory effect on insulin secretion in the presence of glucose supplementation.

This corresponds to an earlier study by Chandler et al. (8), which demonstrated that subjects fed either CHO (55% dextrose, 41% maltodextrin) or CHO and protein mixture (40% dextrose, 30% maltodextrin, 19% milk protein, and 8% whey protein) immediately after a single weight training session (75% of 1RM) had significant increases in their plasma levels of growth hormone, testosterone, and insulin. More recently, Roy et al. (64) demonstrated that glucose supplementation immediately following a single knee extension trial significantly raises postexercise insulin levels. The stimulatory effects demonstrated herein and by others suggest that RE influences pancreatic release of insulin. It is now clear that a single resistance training session provides a strong stimulus for insulin release but is only expressed if glucose is ingested following the activity.

Post-exercise macronutrient intake following endurance exercise can attenuate reductions in body weight and improve nitrogen balance during 7 days of increased energy expenditure. Importantly, post-exercise supplementation improved time to exhaustion during a subsequent bout of endurance exercise (1). Moderate- and high-GI CHO choices appear to enhance glycogen storage after exercise compared with low-GI CHO-rich foods (47).

Restriction of CHO intake does not affect the pattern of changes in plasma GH, and T concentrations during graded exercise but lowers the NA threshold. This indicates an increased sensitivity of the sympathetic nervous system to exercise stimulus. This also alters the basal and exercise levels of circulating hormones, which may have an impact on the balance between anabolic and catabolic processes and subsequently influence the effectiveness of training (40).

Brains role in glucose regulation

As I outlined in Endocrine Insanity Part III, glucose is the primary fuel source for the brain. Interestingly enough, the brain has the ability to regulate blood sugar levels.

Energy in the form of glucose must be constantly supplied to the brain and heart in order for them to function. Thus, blood glucose concentration must be kept at an optimal level of 1g/1 (80-110mg/dl) of plasma. The optimal level of blood glucose is heavily influenced by the neuro-endocrine systems. The hypothalamus (see Endocrine Insanity Part I), provides as a neurohormonal homeostatic system that aims to restore the optimal blood glucose level whenever it deviates significantly from the optimal range. In short, the hypothalamus gland works to keep blood sugar levels at equilibrium.

Hypoglycemia (see Endocrine Insanity Part III) can have serious consequences for brain and heart function.

How does the hypothalamus regulate blood sugar levels?

Special neurons in the hypothalamus gland make up what is called the glucostatic center. These neurons act as sensors and can detect minute changes in blood sugar levels. The neurons have a high metabolic rate, meaning they consume oxygen and glucose at a fast rate. This allows the neurons to detect changes in the level of glucose in the cytoplasm of the cell and consequently in the blood. These neurons are the only cells located in the brain that require insulin for glucose uptake and entry.

The glucostat neurons pick up the signals of low blood sugar in the few hours following a meal. The neurons then activate the hypothalamic feeding (hunger) center. This center increases the appetite and food-seeking behavior. The person is inclined to ingest food, after all, he’s hungry again. From here, the cycle starts over.

Dietary carbohydrates consumed in a meal are absorbed in the intestine, transported via blood and transformed into glucose in the liver which releases glucose back into the bloodstream. This raises the total amount of blood glucose, which induces a brief state of hyperglycemia. Hyperglycemia stimulates the release of insulin from the pancreatic islets (insulin spike). The insulin promotes the entry of glucose into tissues, including the neurons of the glucostatic center.

Hypothalamic glucostat neurons detect the high blood sugar levels which causes them to send output signals to inhibit the feeding control center and activate what is called the satiety control center. The satiety control center is also located in the hypothalamus and is designed to reduce the sensation of hunger - at least for a few hours. The satiety center can also be activated by sensory nerves signaling a distended (enlarged) stomach after food ingestion.

Food ingestion also stimulates the release of hormones  from the walls of the stomach itself. These hormones act on the hypothalamus and signal the body to decrease food intake. The duodenal hormone cholecystokinin (CCK), along with the hormone gastin, are known to exert these short-term feedback effects. Long-term food intake suppression in the hypothalamus is triggered by the fat tissue hormone, leptin.

Catecholamines

In between meals, blood sugar usually drops below optimal levels. When this occurs, the glucostatic center initiates a series of actions to fight this decline in an effort to elevate blood glucose levels to their optimal state. Initially, the glucostatic center signals the hypothalamic center for control of the sympathetic nervous center. Activation of the sympathetic nervous center initiates the release of norepinephrine from the sympathetic nerves and epinephrine from the adrenal medulla. These catecholamines (hormones that function as neurotransmitters) increase glycogenolysis in the liver and lipolysis in adipose tissue (fat cells). Glycogenolysis immediately increases the glucose pool found in the liver. Lipolysis provides glycerol for conversion to glucose in the liver. Added to this, skeletal muscle utilize the fatty acids mobilized from the adipose tissue for energy, sparing more glucose for the heart and the brain.

Roles of growth hormone

When the time in between meals is longer than several hours (such as when we are asleep, fasting, or during long periods of training), blood sugar falls to its lower limit. This stimulates the hypothalamus to release growth-hormone releasing hormone (GHRH). GHRH stimulates the release of growth hormone (GH) from the anterior pituitary gland. The growth hormone acts on fat cells, causing the mobilization of fatty acids and glycerol. The fatty acids and glycerol then go through the process described above. As a result, the blood glucose supply is increased.

In addition to this, growth hormone acts on skeletal muscle tissues to decrease glucose utilization in exchange for the uptake of amino acids. This also spares glucose for the heart and brain.

Role of Cortisol

Cortisol is also released when blood glucose levels are at their lowest. The release of cortisol from the adrenal cortex is stimulated by the hypothalamus via the activation of corticotropin-releasing hormone (CRH). Cortisol is needed so growth hormone can act on fat cells. Cortisol also mobilizes amino acids from skeletal muscle and connective tissue and stimulates their utilization for gluconeogenesis in the liver. Like growth hormone, cortisol decreases glucose utilization by the skeletal muscle and connective tissues in an effort to spare glucose for the heart and brain.

Several other hormones can effect blood glucose levels. The thyroid hormones, T3 and T4, can exhibit effects on blood glucose levels during long-term adaptation to cold weather.

Hypoglycemia

It is a wonder that these systems work synergistically together. They are beautifully designed! However, if these systems should fail, disaster strikes.

During prolonged starvation, these systems begin to fall apart and ultimately fail. Blood glucose levels will inevitably fall below critical limits as the heart and brain continue their consumption of glucose. When the blood glucose levels drop below 60mg/dl, the heart begins to weaken and nervous, cognitive, and conscious activities become disturbed. Below 50mg/dl, speech becomes slurred and movement becomes uncoordinated. When blood glucose levels drop below 30mg/dl, unconsciousness and coma are inevitable. At 20mg/dl convulsions may occur and at 10mg/dl, permanent brain damage occurs and a loss of medullary respiratory centers causes death.

As you can clearly see, these systems must be working optimally to sustain life. It is a wonder that they do this so effectively!

The  liver

All the hormones acting to regulate blood sugar do so in part by acting on the liver. The liver contains special membrane and nuclear receptors for these hormones along with a variety of intracellular second messengers and signaling systems (cyclic AMP). These systems mediate the effects of the hormones and receptors.

The liver, via the portal vein, has direct access to the carbohydrates absorbed from the intestine. This makes the liver the immediate center for the synthesis, delivery, storage and production of glucose. The liver takes up a large portion of the abundant blood glucose after meals. This task is performed by glucose transporters located in the liver. These transporters are not dependent on insulin (insulin insensitive GluT2).

The liver is the major organ regulating the homeostasis of carbohydrate metabolism generally, and blood sugar specifically. The liver produces enzymes which convert glycogen to glucose and visa versa. Approximately 500 grams of glycogen is stored in the liver at a given time. Based on the assumption that this equals 500 grams of glucose, then the liver contains 100 times more glucose than the whole blood stream.

Because the liver contains a special enzyme, glucose-6-phosphatase, that hydrolyzes the glucose-6-phosphate to free glucose, it is the only organ in the body that can secrete glucose into the blood when the level of glucose in the liver exceeds that of the blood. The liver also converts glycerol to glucose and visa versa. And amino acids to glucose and visa versa. But the liver cannot synthesize glucose from fatty acids.

Glycemic index

The glycemic index (GI) provides a way to rank foods rich in carbohydrate according to the glucose response following their intake. Consumption of low-GI CHO-rich foods may attenuate the insulin-mediated metabolic disturbances associated with CHO intake in the hours prior to exercise, better maintaining CHO availability (47).

This index measures how much your blood sugar increases in two or three hours after eating. There are a number of misconceptions that virtually everyone has about the glycemic index. In fact, there are occasions when you'll need to ditch the glycemic index list of foods altogether, and use a far easier method based on the energy density of a given food.

In the 1970’s, carbohydrates were known as either simple or complex. Foods high in sugar, such as chocolate, fruit or cakes were classed as simple carbohydrates. At the time, scientists thought these foods were quickly digested, leading to a rapid rise in blood sugar. Complex carbohydrates, such as potatoes, rice and pasta were supposed to break down more slowly, producing a gradual rise in blood sugar.

This all changed when Dr. David Jenkins Began working on diabetes patients. He discovered that some complex carbohydrates actually caused a rapid rise in blood sugar. Other foods that were known as simple carbs caused blood sugar to be elevated slowly. Dr. Jenkins’ research led scientists to begin classifying carbohydrates based on their rating on the Glycemic Index.

Foods that digest rapidly lead to a fast release of glucose into your blood stream. These are known as high glycemic index foods. Foods that digest slowly release glucose into your blood gradually, and are known as low Glycemic Index foods (47).

The glycemic index assigns a numerical value to food rich in carbohydrates. The number represents how much and how rapidly 50 grams of its carbohydrate content will raise blood sugar compared to 50 grams of the reference food (glucose).