Trans_Isomer
July 28th, 2006, 04:28 PM
Hormonal Interplay: Primer
Authors Note: I mainly became interested in writing this article after much research and reading into the regulatory roles insulin and glucagon play. I hope this article provides a good basis for the next set of articles I hope to see come to light, mainly concerning the pre/peri-workout timeframe. The article is part of a ‘primer’ series I hope to continue writing, that provides a good basis for understanding the principles set forth in the next set of articles. If you are looking at ways to drop fat, this article is a good read, if your looking for ways to set up a diet, this article is a good read, if your looking for ways to set up a pre/peri-workout plan, this article is a good basis to that as well.
- Trans_Isomer
INSULIN
Ingested carbohydrate enters the bloodstream as glucose. In response, the pancreas secretes the hormone insulin to shuttle the glucose to target tissue. Insulin is a peptide (protein based) regulatory hormone that determines the levels of other hormones in the body, its primary role being to keep blood glucose within a range of 80-120mg/dl. The greatest stimulator of insulin secretion is ingested carbohydrate. Protein is converted to glucose with 58% efficiency, and fat being the third with a conversion rate of about 10%. Excess carbohydrate is stored as alpha-glycerophosphate in fat cells by a process called de novo lipogenesis. Insulin stimulates protein synthesis by moving free amino acids into the muscle, where larger muscle proteins are constructed. Fat synthesis (lipogenesis) and fat storage are stimulated with when insulin levels increase. Fat oxidation is suppressed as free fatty acid release from fat cells is inhibited when insulin levels are high.
Figure 1 Insulin
http://i25.photobucket.com/albums/c70/Trans_Isomer/250px-InsulinMonomer.jpg
GLUCAGON
Glucagon is insulin’s ‘mirror’ hormone. When insulin is up, glucagon is down. When glucagon is up, insulin is down. It has opposite effects that of insulin, being a fuel-mobilizing, or “liberating” hormone. Glucagon exerts its effects mainly in the liver where it breaks down glycogen. Glucagon is also a regulatory hormone in that glucagon levels in the body determine the levels of other hormones in the body. Glucagon, along with the catecholamines, (adrenaline, noradrenaline) stimulate the break down of free fatty acids and glycerol from stored adipose tissue triglyceride. Proteins may be broken down into individual amino acids (Proteolysis) for conversion to glucose, a role in which cortisol also plays.
Figure 2 Glucagon
http://i25.photobucket.com/albums/c70/Trans_Isomer/200px-Glucagon.png
INTERPLAY
Insulin being the storage hormone moves nutrients from the bloodstream to target tissues. Glucagon being the fuel-mobilizing hormone, when its levels are up, fat oxidation is ramped up, and so are the levels of the catecholamines and other key hormones. Since glucagon is suppressed by insulin, one can see that carbs, being the main stimulator of insulin, keep the body in a state of "storage" rather than "liberation" meaning less fat is being burned. The body has no reason to break down adipose tissue triglyceride since there is plenty of circulating glucose in the body. Thus, we see the fate of the typical "bulk" type diet, the dreaded increase in BF percent. Constantly eating carbs throughout the day, insulin stays elevated, and no fat oxidation (lipolysis) occurs. Though insulin is anabolic, we also must remember it is a storage hormone.
The levels in which insulin and glucagon are in comparison to one another, is referred to as the insulin/glucagon ratio (I/G ratio). Insulin has a stronger fat oxidation suppressing effect (anti-lipolytic) than the catecholamines have a fat burning (lipolytic) effect. This means that even if the fat burning catecholamine levels are high, if insulin levels are high as well, fat oxidation will be suppressed. As insulin drops free fatty acid’s (FFA) are mobilized and used as fuel for the liver to make ketones. Since liver glycogen is depleted CPT-1 becomes active burning the incoming FFA which then produces acetyl-CoA.
There are four distinct fuels the body can use as fuel:
1) Glucose
2) Protein
3) Free Fatty Acids (FFA)
4) Ketones
The ratios of the above used by the body are determined by the metabolic state of the body.
In the absence of dietary carbohydrate, Insulin levels decrease and thus glucagon levels then increase. As the insulin levels drop Free Fatty Acids (FFA) are mobilized from the fat cell, proving fuel for the liver to make ketones. Liver glycogen becomes depleted, and CPT-1 becomes active. CPT-1 burns the incoming FFA which in turn produces acetly-CoA; acetyl-CoA accumulates and condenses into ketones. The primary regulator of ketogenesis in the liver is a substance called malonyl-CoA.
Consumption of carbs on a day to day basis, as with a ‘balanced’ diet, our body’s metabolism stays based on glucose. Carbohydrate stores in the body are very small compared to protein and fat stores, being mainly stored as muscle and liver glycogen. If liver glycogen is completely depleted, blood glucose then drops, and a shift in insulin and glucagon occurs, thus inducing ketogenesis, the formation of ketone bodies. Ultimately the main determinant of fuel use by the body is carbohydrate ingestion.
In a 150lb man with 22% bodyfat, the average total carbohydrate stores are 0.8lbs (840 kcal worth) while adipose tissue triglyceride stores are 33lbs with a caloric worth of 135,000 kcals. The point being that the majority source of glucose that the body uses comes from diet, not from bodily stores.
Free Fatty Acids (FFA) and Ketones
When dietary carbohydrate is restricted the body will break down free fatty acids, glycerol from stored adipose tissue triglyceride for conversion to glucose, along with proteins (gluconeogenesis). Most tissues on the body can use free fatty acids, but the brain cannot. It uses ketones in place of glucose, when glucose availability is low. In addition to the brain, red blood cells, the renal medulla, bone marrow, and Type II muscle fibers cannot use FFA, and therefore rely on ketones for fuel.
A great misconception is that the brain can only use glucose for fuel. Though it is a preferred fuel source, the brain will readily use ketones in place of glucose. An increase in FFA levels will decrease the need for glucose by the body.
The primary regulators of ketone body production are the hormones insulin and glucagon. The three ketone bodies are acetoacetate (AcAc), beta-hydroxybutyrate (BHB) and acetone. There most important role is to replace glucose as a fat derived fuel for the brain. The brain can derive 75% of its total energy requirements from ketones after adaptation has occurred.
Ketone availability is based upon carbohydrate/glucose availability by the body. When the body is getting plenty of carbohydrate/glucose from the diet, ketone production is minimal and concentrations are so low that there is a negligible amount of energy provided to the tissues of the body. Ketones are thought to act as the ‘signal’ for the body to switch from using glucose as fuel, to using fat for fuel. Ketones serve as a fuel for tissues in the body. When the body’s metabolism is switched from a glucose based metabolism to a fat based metabolism, the available glucose is conserved for use by the brain.
The breakdown of fat as discussed above is regulated by the catecholamines and insulin/glucagon. When insulin is high, free fatty acid mobilization is inhibited and fat storage is stimulated. When insulin levels decrease free fatty acids are mobilized due to the presence of the catecholamines, such as adrenaline and noradrenaline with additional roles played by growth hormone, glucagon, and cortisol.
When these “fat burning” signals are sent, stored adipose tissue triglyceride is broken down into glycerol and three free fatty acid chains, hence the name ‘tri’glyceride. The free fatty acids, now in the bloodstream become bound to a protein called albumin. The FFA now in the bloodstream are used for energy, and are converted in the liver to ketones for use by the brain, red blood cells, renal medulla, bone marrow, and type II muscle fibers, all of which cannot use FFA for fuel.
Thus we can see the process as follows: the process of burning adipose tissue triglyceride occurs like this:
1) Triglyceride (3 fatty acids and a glycerol) are mobilized due to high glucagon/catecholamine levels (low insulin levels)
2) Glycerol is released into the bloodstream to be converted to glucose in the liver
3) Adrenaline and Noradrenaline bind to beta-adrenergic receptors in the fat cell which stimulates the release of FFA into the bloodstream
4) Broken down FFA now travel through the bloodstream to the muscle or liver
5) Inside the cell, the mitochondria burn the incoming FFA which yields ATP and acetyl-CoA. The acetyl-CoA being used to produce more energy within the muscle.
One molecule of FFA yields 129-300 ATP or more compared to the 36-39 ATP produced from glucose. As you can see, fats provide far more energy.
Gluconeogenesis
When dietary carbohydrate intake is restricted, the body will use amino acids, glycerol, lactate, and pyruvate to convert to glucose. This is called gluconeogenesis. ‘Gluco’ meaning glucose, ‘neo’ meaning new, and ‘genesis’ meaning creation, the new creation of glucose. Gluconeogenesis proceeds in the liver and kidneys as a means to create glucose for the body. Initially when dietary carbohydrate is restriced, the body breaks down its own stores of protein to create glucose. The body will never be in a 100% non-use state of glucose. Even when the diet is devoid of carbohydrate, glucose will be produced in the body, though its levels will not be as high as when dietary
carbohydrates are ingested.
The points to take home from this are that in an elevated insulin state, the fat burning mechanisms of the body will be suppressed. The levels of glucagon, adrenaline, noradrenaline, cortisol, and growth hormone are all suppressed when insulin is elevated. These facts provide implications onto how to set up an optimal fat ‘burning’ diet, and also how to set up an optimal pre/peri-workout scheme. The next set of articles shall provide further insight to this as well.
T_I
References:
-Mcdonald, Lyle. The Ketogenic Diet: A Complete Guide for the Dieter and Practioner
-McGarry JD et. al. Regulation of ketogenesis and the renaisance of carnitine palmitoyltransferase. Diabetes/Metab Rev (1989) 5:271-284.
-Foster D. Banting Lecture 1984 - From Glycogen to Ketones - and back. Diabetes (1984) 33: 1188-1199
-Cahill G. Starvation in man. N Engl J Med (1970) 282: 668-675
-Owen O.E. et. Al. Brain metabolism during fasting. J Clin Invest (1967) 10: 1589-1595
-Sokoloff L. Metabolism of ketone bodies by the brain. Ann Rev Med (1973) 24: 271-280
-Cahill G. Ketosis. Kidney International (1981) 20: 416-425
-Mitchell GA et. Al. Medical aspects of ketone body metabolism. Clinical & Investigative Medicine (1995) 18:193-216
-Swink TD et. Al. The ketogenic diet: 1997: Adv Pediatr (1997) 44: 297-329
-Flatt JP. McCollum Award Lecture, 1995: Diet, lifestyle, and weight maintenance. AM J Clin Nutr (1995) 62: 820-836
-Cahill GF Jr. et. Al. Hormone-fuel relationships during fasting. J Clin Invest (1966) 45: 1751-1769
-Arner P. Impact of exercise on adipose tissue metabolism during exercise. Int J Obesity (1995) 19 Suppl 3: S18-S21.
-Jungas RL et. Al. Quantitative analysis of amino acid oxidation and related gluconeogenesis in human. Physiological Reviews (1992) 72: 419-448
-Fat metabolism during exercise: a review--part II: regulation of metabolism and the effects of training.
Jeukendrup AE, Saris WH, Wagenmakers AJ.
-Regulatory mechanisms in the interaction between carbohydrate and lipid oxidation during exercise.
Spriet LL, Watt MJ.
-Modulation of carbohydrate and fat utilization by diet, exercise and environment.
Jeukendrup AE.
-Glucose ingestion during exercise blunts exercise-induced gene expression of skeletal muscle fat oxidative genes.
Civitarese AE, Hesselink MK, Russell AP, Ravussin E, Schrauwen P.
-Images from wikipedia.com
Authors Note: I mainly became interested in writing this article after much research and reading into the regulatory roles insulin and glucagon play. I hope this article provides a good basis for the next set of articles I hope to see come to light, mainly concerning the pre/peri-workout timeframe. The article is part of a ‘primer’ series I hope to continue writing, that provides a good basis for understanding the principles set forth in the next set of articles. If you are looking at ways to drop fat, this article is a good read, if your looking for ways to set up a diet, this article is a good read, if your looking for ways to set up a pre/peri-workout plan, this article is a good basis to that as well.
- Trans_Isomer
INSULIN
Ingested carbohydrate enters the bloodstream as glucose. In response, the pancreas secretes the hormone insulin to shuttle the glucose to target tissue. Insulin is a peptide (protein based) regulatory hormone that determines the levels of other hormones in the body, its primary role being to keep blood glucose within a range of 80-120mg/dl. The greatest stimulator of insulin secretion is ingested carbohydrate. Protein is converted to glucose with 58% efficiency, and fat being the third with a conversion rate of about 10%. Excess carbohydrate is stored as alpha-glycerophosphate in fat cells by a process called de novo lipogenesis. Insulin stimulates protein synthesis by moving free amino acids into the muscle, where larger muscle proteins are constructed. Fat synthesis (lipogenesis) and fat storage are stimulated with when insulin levels increase. Fat oxidation is suppressed as free fatty acid release from fat cells is inhibited when insulin levels are high.
Figure 1 Insulin
http://i25.photobucket.com/albums/c70/Trans_Isomer/250px-InsulinMonomer.jpg
GLUCAGON
Glucagon is insulin’s ‘mirror’ hormone. When insulin is up, glucagon is down. When glucagon is up, insulin is down. It has opposite effects that of insulin, being a fuel-mobilizing, or “liberating” hormone. Glucagon exerts its effects mainly in the liver where it breaks down glycogen. Glucagon is also a regulatory hormone in that glucagon levels in the body determine the levels of other hormones in the body. Glucagon, along with the catecholamines, (adrenaline, noradrenaline) stimulate the break down of free fatty acids and glycerol from stored adipose tissue triglyceride. Proteins may be broken down into individual amino acids (Proteolysis) for conversion to glucose, a role in which cortisol also plays.
Figure 2 Glucagon
http://i25.photobucket.com/albums/c70/Trans_Isomer/200px-Glucagon.png
INTERPLAY
Insulin being the storage hormone moves nutrients from the bloodstream to target tissues. Glucagon being the fuel-mobilizing hormone, when its levels are up, fat oxidation is ramped up, and so are the levels of the catecholamines and other key hormones. Since glucagon is suppressed by insulin, one can see that carbs, being the main stimulator of insulin, keep the body in a state of "storage" rather than "liberation" meaning less fat is being burned. The body has no reason to break down adipose tissue triglyceride since there is plenty of circulating glucose in the body. Thus, we see the fate of the typical "bulk" type diet, the dreaded increase in BF percent. Constantly eating carbs throughout the day, insulin stays elevated, and no fat oxidation (lipolysis) occurs. Though insulin is anabolic, we also must remember it is a storage hormone.
The levels in which insulin and glucagon are in comparison to one another, is referred to as the insulin/glucagon ratio (I/G ratio). Insulin has a stronger fat oxidation suppressing effect (anti-lipolytic) than the catecholamines have a fat burning (lipolytic) effect. This means that even if the fat burning catecholamine levels are high, if insulin levels are high as well, fat oxidation will be suppressed. As insulin drops free fatty acid’s (FFA) are mobilized and used as fuel for the liver to make ketones. Since liver glycogen is depleted CPT-1 becomes active burning the incoming FFA which then produces acetyl-CoA.
There are four distinct fuels the body can use as fuel:
1) Glucose
2) Protein
3) Free Fatty Acids (FFA)
4) Ketones
The ratios of the above used by the body are determined by the metabolic state of the body.
In the absence of dietary carbohydrate, Insulin levels decrease and thus glucagon levels then increase. As the insulin levels drop Free Fatty Acids (FFA) are mobilized from the fat cell, proving fuel for the liver to make ketones. Liver glycogen becomes depleted, and CPT-1 becomes active. CPT-1 burns the incoming FFA which in turn produces acetly-CoA; acetyl-CoA accumulates and condenses into ketones. The primary regulator of ketogenesis in the liver is a substance called malonyl-CoA.
Consumption of carbs on a day to day basis, as with a ‘balanced’ diet, our body’s metabolism stays based on glucose. Carbohydrate stores in the body are very small compared to protein and fat stores, being mainly stored as muscle and liver glycogen. If liver glycogen is completely depleted, blood glucose then drops, and a shift in insulin and glucagon occurs, thus inducing ketogenesis, the formation of ketone bodies. Ultimately the main determinant of fuel use by the body is carbohydrate ingestion.
In a 150lb man with 22% bodyfat, the average total carbohydrate stores are 0.8lbs (840 kcal worth) while adipose tissue triglyceride stores are 33lbs with a caloric worth of 135,000 kcals. The point being that the majority source of glucose that the body uses comes from diet, not from bodily stores.
Free Fatty Acids (FFA) and Ketones
When dietary carbohydrate is restricted the body will break down free fatty acids, glycerol from stored adipose tissue triglyceride for conversion to glucose, along with proteins (gluconeogenesis). Most tissues on the body can use free fatty acids, but the brain cannot. It uses ketones in place of glucose, when glucose availability is low. In addition to the brain, red blood cells, the renal medulla, bone marrow, and Type II muscle fibers cannot use FFA, and therefore rely on ketones for fuel.
A great misconception is that the brain can only use glucose for fuel. Though it is a preferred fuel source, the brain will readily use ketones in place of glucose. An increase in FFA levels will decrease the need for glucose by the body.
The primary regulators of ketone body production are the hormones insulin and glucagon. The three ketone bodies are acetoacetate (AcAc), beta-hydroxybutyrate (BHB) and acetone. There most important role is to replace glucose as a fat derived fuel for the brain. The brain can derive 75% of its total energy requirements from ketones after adaptation has occurred.
Ketone availability is based upon carbohydrate/glucose availability by the body. When the body is getting plenty of carbohydrate/glucose from the diet, ketone production is minimal and concentrations are so low that there is a negligible amount of energy provided to the tissues of the body. Ketones are thought to act as the ‘signal’ for the body to switch from using glucose as fuel, to using fat for fuel. Ketones serve as a fuel for tissues in the body. When the body’s metabolism is switched from a glucose based metabolism to a fat based metabolism, the available glucose is conserved for use by the brain.
The breakdown of fat as discussed above is regulated by the catecholamines and insulin/glucagon. When insulin is high, free fatty acid mobilization is inhibited and fat storage is stimulated. When insulin levels decrease free fatty acids are mobilized due to the presence of the catecholamines, such as adrenaline and noradrenaline with additional roles played by growth hormone, glucagon, and cortisol.
When these “fat burning” signals are sent, stored adipose tissue triglyceride is broken down into glycerol and three free fatty acid chains, hence the name ‘tri’glyceride. The free fatty acids, now in the bloodstream become bound to a protein called albumin. The FFA now in the bloodstream are used for energy, and are converted in the liver to ketones for use by the brain, red blood cells, renal medulla, bone marrow, and type II muscle fibers, all of which cannot use FFA for fuel.
Thus we can see the process as follows: the process of burning adipose tissue triglyceride occurs like this:
1) Triglyceride (3 fatty acids and a glycerol) are mobilized due to high glucagon/catecholamine levels (low insulin levels)
2) Glycerol is released into the bloodstream to be converted to glucose in the liver
3) Adrenaline and Noradrenaline bind to beta-adrenergic receptors in the fat cell which stimulates the release of FFA into the bloodstream
4) Broken down FFA now travel through the bloodstream to the muscle or liver
5) Inside the cell, the mitochondria burn the incoming FFA which yields ATP and acetyl-CoA. The acetyl-CoA being used to produce more energy within the muscle.
One molecule of FFA yields 129-300 ATP or more compared to the 36-39 ATP produced from glucose. As you can see, fats provide far more energy.
Gluconeogenesis
When dietary carbohydrate intake is restricted, the body will use amino acids, glycerol, lactate, and pyruvate to convert to glucose. This is called gluconeogenesis. ‘Gluco’ meaning glucose, ‘neo’ meaning new, and ‘genesis’ meaning creation, the new creation of glucose. Gluconeogenesis proceeds in the liver and kidneys as a means to create glucose for the body. Initially when dietary carbohydrate is restriced, the body breaks down its own stores of protein to create glucose. The body will never be in a 100% non-use state of glucose. Even when the diet is devoid of carbohydrate, glucose will be produced in the body, though its levels will not be as high as when dietary
carbohydrates are ingested.
The points to take home from this are that in an elevated insulin state, the fat burning mechanisms of the body will be suppressed. The levels of glucagon, adrenaline, noradrenaline, cortisol, and growth hormone are all suppressed when insulin is elevated. These facts provide implications onto how to set up an optimal fat ‘burning’ diet, and also how to set up an optimal pre/peri-workout scheme. The next set of articles shall provide further insight to this as well.
T_I
References:
-Mcdonald, Lyle. The Ketogenic Diet: A Complete Guide for the Dieter and Practioner
-McGarry JD et. al. Regulation of ketogenesis and the renaisance of carnitine palmitoyltransferase. Diabetes/Metab Rev (1989) 5:271-284.
-Foster D. Banting Lecture 1984 - From Glycogen to Ketones - and back. Diabetes (1984) 33: 1188-1199
-Cahill G. Starvation in man. N Engl J Med (1970) 282: 668-675
-Owen O.E. et. Al. Brain metabolism during fasting. J Clin Invest (1967) 10: 1589-1595
-Sokoloff L. Metabolism of ketone bodies by the brain. Ann Rev Med (1973) 24: 271-280
-Cahill G. Ketosis. Kidney International (1981) 20: 416-425
-Mitchell GA et. Al. Medical aspects of ketone body metabolism. Clinical & Investigative Medicine (1995) 18:193-216
-Swink TD et. Al. The ketogenic diet: 1997: Adv Pediatr (1997) 44: 297-329
-Flatt JP. McCollum Award Lecture, 1995: Diet, lifestyle, and weight maintenance. AM J Clin Nutr (1995) 62: 820-836
-Cahill GF Jr. et. Al. Hormone-fuel relationships during fasting. J Clin Invest (1966) 45: 1751-1769
-Arner P. Impact of exercise on adipose tissue metabolism during exercise. Int J Obesity (1995) 19 Suppl 3: S18-S21.
-Jungas RL et. Al. Quantitative analysis of amino acid oxidation and related gluconeogenesis in human. Physiological Reviews (1992) 72: 419-448
-Fat metabolism during exercise: a review--part II: regulation of metabolism and the effects of training.
Jeukendrup AE, Saris WH, Wagenmakers AJ.
-Regulatory mechanisms in the interaction between carbohydrate and lipid oxidation during exercise.
Spriet LL, Watt MJ.
-Modulation of carbohydrate and fat utilization by diet, exercise and environment.
Jeukendrup AE.
-Glucose ingestion during exercise blunts exercise-induced gene expression of skeletal muscle fat oxidative genes.
Civitarese AE, Hesselink MK, Russell AP, Ravussin E, Schrauwen P.
-Images from wikipedia.com