The Insulin, Glucagon & Weight Gain
Insulin is a large polypeptide hormone secreted by the beta-cells of the pancreas. Its release is directly controlled by dietary factors. Blood sugar is the principal stimulus to insulin secretion. Insulin lowers the concentration of glucose in blood by inhibiting liver glucose production and by stimulating the uptake of glucose by muscle and adipose tissue. Normally, insulin inhibits the breakdown of stored body fat, stimulates fatty acid synthesis and decreases the liver concentration of carnitine which "shuttles" fatty acids into mitochondria in most cells for use as ATP energy fuel. Insulin stimulates the fat cells to take up fat and sugar from the blood and store it away as body fat, causing weight gain especially in the middle of the body, within the abdomen and around the vital organs.
Overweight people have higher baseline levels of insulin; which promotes fat-formation leading to weight gain. Eating a candy or drinking a soft drink will normally raise blood sugar - and blood insulin - within minutes. The modern industrialized starches, such as white flour and finely ground corn meal, used to make pasta, bread, cakes, corn chips and tortillas, crackers, cookies, etc., are digested and absorbed almost as quickly as simple sugar foods leading to weight gain.
Insulin regulates blood sugar working together with another hormone “glucagon” which is also secreted by the pancreas. Glucose is a potent inhibitor of Glucagon. Insulin opposes the effect of Glucagon and is always dominant in equal doses. Glucagon levels are increased with dietary protein, while insulin levels increase with dietary carbohydrate. Just as insulin lowers high blood sugar, glucagon raises low blood sugar, when we skip meals; exercise severely, fast, starvation diet, etc.
There are two enzymes on the surface of the fat cells responsible for fat mobilization into or out of the fat cells. The first, lipoprotein lipase , transports fatty acids into the fat cell while the other, hormone-sensitive lipase, releases the fat from fat cells into the blood to be "burned" as fuel. Insulin stimulates the activity of lipoprotein lipase, the fat-storage enzyme causing weight gain, and glucagon inhibits it; glucagon stimulates the fat-releasing hormone facilitating weight loss, and insulin inhibits it. By altering the ratio of insulin to glucagon we can determine which pathway predominates. In the insulin-dominant mode, fat storage prevails leading to weight gain. In the glucagon-dominant mode, fat flows away from the fat cells promoting weight loss. Fat released from the fat cells enters the other cells and gets shuttled into the mitochondria, where it is completely burned for cellular energy. Along with this fat from the fat cells any dietary fat - whether consumed as fat or converted from carbohydrate or protein - also flows into the mitochondria for oxidation instead of into the fat cells to be stored."
According to Barry Sears, there are four chief "pillars of aging" that promote ever-worsening hormonal regulation of and communication between cells, ultimately leading to aging, disease and death.
- Excess insulin.
- Excess cortisol.
- Excess blood glucose.
- Excess free radicals.
Metabolic Syndrome - X.
This is a syndrome common among sedentary modern Western humans, which involves the strong clustering of hypertension, insulin resistance, hyperinsulinemia, hyper-triglyceridemia, glucose intolerance, obesity, low HDL cholesterol and heart disease. It has been shown that the common denominator of the syndrome is hyperinsulinemia and insulin resistance. Aging increases the tendency to develop the condition of insulin resistance, wherein the target cells of insulin - especially the muscle cells - become even more resistant to "hearing the message" of insulin. This in turn lessens the blood sugar-lowering effect of insulin, so that even-smaller amounts of sugar lead to ever-higher blood glucose levels - i.e. glucose intolerance. As cells become more resistant to the insulin, it starts building up. Insulin is known to cause sodium retention with consequent water retention resulting in high blood pressure. As already noted, insulin promotes fat storage in fat cells - i.e. obesity and weight gain. Insulin stimulates the liver to convert sugar and dietary fats into triglycerides - the form of fat that circulates in the blood and is stored in fat cells - i.e. hyper-triglyceridemia. Insulin promotes proliferation of arterial smooth muscle cells which is initial phase of atherosclerotic plaque formation and enhances lipid synthesis and low-density lipoprotein or LDL receptor activity.
Insulin resistance has been induced in normal human subjects by overfeeding. The onset of glucose intolerance may be due to frequent snacking on high energy density foods which prevent insulin levels from returning to normal fasting levels keeping insulin circulating in the blood for a better part of the 24-hour day. If levels edge chronically higher, cells must become somewhat insulin resistant. Because most cells can burn either fat or glucose for fuel, but the brain under normal circumstances can only burn glucose and typically needs 400 - 500 calories/day of glucose - i.e. about one half the normal total circulating blood sugar.
Thus in order to safeguard the brain's minute-by-minute blood glucose delivery, other cells must develop insulin resistance when insulin levels are frequently or chronically high, so that they don't "snatch" all the blood glucose from the hungry brain. The primary hormone that should raise blood sugar to adequately feed the brain is glucagon. But "insulin can act as a glucagon release-inhibiting paracrine hormone," especially at high concentrations. So then the body releases cortisol to take charge.
Cortisol & Weight Gain
Cortisol comes to the brain's rescue in two ways. It increases the making of glucose by breaking down proteins from skin, muscle and organ tissue and converting them to glucose in the liver. "Cortisol also causes a moderate decrease in the rate of glucose utilization by cells everywhere in the body” i.e. cortisol causes insulin resistance! Thus the three pillars of aging - excess insulin, cortisol and blood glucose - are all interlocking and mutually enhancing. And not only does cortisol causes breakdown of precious body protein to make blood sugar, it also weakens the immune system and damages hippocampal neurons – similar to Alzheimer's disease.
Cortisol also contributes significantly to obesity. Adrenal corticosteroids also play a role in the development of hypothalamic obesity, glucose obesity, and dietary obesity all leading to excess weight gain. Thus, the substrate for essentially all forms of obesity rests on cortisol secretion from the adrenal gland. Cortisol is also secreted to raise blood sugar in those who frequently skip meals, are fasting, practice "starvation dieting", or are under severe stress.
Hormonal Communication & Weight Gain
Most hormones deliver their "message" by interacting with specific receptors on outer cell membrane surfaces, although some do penetrate directly into the cell as well. When hormones bind to their appropriate cellular receptors, they normally activate substances inside the cell known as "second messengers. These second messengers actually induce the hormonal biological effect inside the cell. Insulin acts through the second messengers’ inositol triphosphate (IP3) and diacylglycerol (DAG).
Perhaps the commonest second messenger, however, is cyclic AMP (cAMP). "Many hormones do appear to utilize cAMP as a second messenger, including calcitonin, chorionic gonadotrophin, corticotrophin, epinephrine [adrenalin], follicle-stimulating hormone [FSH], glucagon, luteinizing hormone [LH], lipotrophin, melanocyte-stimulating hormone [MSH], norepinephrine [noradrenaline], parathyroid hormone, thyroid-stimulating hormone [TSH], and vasopressin."
Thus, not only are insulin and glucagon opposite in their basic physiologic actions, they were opposing second messengers: IP3/DAG vs. cAMP. If a cell has multiple hormone receptors, then the final biological response of the cell depends on which second messenger system (cAMP or IP3/DAG) predominates at that point in time." When hormones such as noradrenaline or glucagon bind to their cell membrane receptors, they activate an enzyme called "adenylate cyclase." This enzyme then produces the cAMP second messenger inside the cell. Unfortunately insulin opposes cyclic AMP production by adenylate cyclase.
Insulin is one of the few hormones (cortisol being the other major one) which increases with age - most others, such as thyroid, DHEA, testosterone, estrogen, growth hormone, etc. decrease with age. Most of the hormones which use cAMP as their second messenger, suffer decreased secretion with aging. Since insulin generally increases with age, but opposes cAMP, while most hormones that act through cAMP decrease with age, it is obvious that hyperinsulinemia will tend to distort the overall "symphony" of hormone interactions, and thus promote poor hormonal communication.
Growth Hormone, Testosterone, Estrogen & Weight Gain
Growth hormone (GH) and insulin have both complementary and antagonistic properties. GH and insulin are both anabolic - they facilitate the growth of lean body mass - i.e. muscle, organ tissue, tendons, bones, etc. When animals are surgically deprived of both hormones, growth ceases. Giving either GH or insulin alone causes virtually no increase in growth, but giving them both together restores normal growth.
In other ways, these hormones are opposites: GH promotes fat burning/loss, promotes weight loss targeting the extra fat, while insulin opposes fat burning and promotes fat gain/ weight gain. Increased insulin levels and decreased GH levels are characteristic of obesity and weight gain. PGE1 suppresses insulin release while PGE1 increases pituitary GH release. Aging pituitaries may still produce adequate GH - it's the releasing of GH that seems to become problematic with age. Perhaps not surprisingly, GH-releasing hormone requires adequate pituitary cAMP levels to perform its GH-releasing "magic." Also, a factor that can decrease pituitary GH-production is elevated insulin, which may inhibit GH synthesis. Thus lowering insulin through a low-CHO diet combined with GLA/EPA supplements to enhance PGE1/cAMP levels is a natural way to restore age-declining GH function and for natural weight loss.
While GH can stimulate fat-burning and weight loss by itself, it helps to build muscle mass when combined with its normal synergist - testosterone. In both men and women, testosterone is produced through the combined action of pituitary-released follicle-stimulating hormone (FSH) and luteinizing hormone (LH), acting on the ovaries in women and Leydig cells of the testes in men. Yet both FSH and LH act through the second messenger cAMP. Thus obesity/high CHO diet-elevated insulin will tend to inhibit the testosterone-producing activity of FSH/LH.
The problem doesn't end there, however. In both men and women, testosterone may be converted to estrogen through an aromatase enzyme. And the aromatase enzyme exists and functions primarily in body fat! Furthermore, estrogen is itself a powerful pro-fat hormone: "In addition to deposition of fat in the breasts and subcutaneous tissues, estrogens cause the deposition of fat in the buttocks and thighs. Indeed, insulin, estrogen and cortisol are the three primary pro-fat hormones of the human body.
Another threat to normal male testosterone levels is severe, chronic stress. Both testosterone and cortisol are made from the precursor protohormone, pregnenolone. Normal daily male testosterone production is 5mg, while 10-20mg of cortisol is produced daily under non-stressed life conditions. The amount of cortisol produced under stress may double, perhaps "stealing" lowering Pregnenolone with age which is needed for testosterone production. As noted earlier, cortisol is extremely pro-fat, and is the chief agent of muscle breakdown, directly opposing testosterone's anabolic muscle-building action.