In this video and the next, I will address the role of the Endocrine System in regulating many essential physiological and biochemical adjustments made by the body in response to exercise. The Endocrine System is a collection of glands that produce and secrete specific hormones into the blood. While there are numerous endocrine glands in the body, I will focus on only three. The pancreas is responsible for the production and release of insulin and glucagon. Both of which play a critical role in carbohydrate metabolism during exercise. The adrenal glands and specifically the adrenal medulla produce epinephrine and norepinephrine which have multiple effects in the regulation of many key physiological and biochemical adjustments made by the body in response to exercise. Finally, I will adjust the role of the growth hormone released from the anterior pituitary gland. First, let's briefly review some of the basic characteristics of hormones. Hormones are trace substances produced and secreted by various endocrine glands which are then carried in the blood to various target tissues. At this target tissues, hormones regulate a variety of physiologic and metabolic functions as they react with their specific receptors present in or on target tissues. As they circulate in the blood, hormones have the ability to reach all tissues in the body. Lastly, I wish to emphasize that the endocrine system works closely with the nervous system to maintain homeostasis during the physical stress of exercise. Let's begin with the hormone insulin. Insulin is produced and secreted from the beta cells in the pancreas. It is responsive after a meal when the blood is rich in macronutrients, with an elevation of blood glucose concentration be in a major stimulus for its release. Shown here is the normal fasting range for blood glucose levels. Ideally in healthy adults, blood glucose levels should be between 70 and 100 milligrams of glucose per 100 milliliters of blood. In this figure, the insulin response after a meal, when blood glucose levels are high as indicated by the blue arrows. The increase in blood glucose levels directly stimulates the pancreas to release insulin into the blood thereby elevating blood insulin levels. Insulin will now promote glucose uptake in most cells for fuel. But in the case of skeletal muscle and the liver, the glucose taken up will be primarily used to replenish your glycogen stores that have been somewhat depleted since your last meal. This table demonstrates the metabolic effects of insulin on glucose uptake and storage as glycogen in muscle and liver. Please notice that once these glycogen stores have been completely replenished, any excess glucose from the meal will be converted into fat in both liver and adipose tissue. We will revisit this concept when we discuss weight control and obesity in module four. Whether you are engaging in sub-maximal steady state exercise, or a graded exercise test to exhaustion, insulin levels decline during exercise. This decline in blood insulin levels when coupled with the reduction in blood flow to not active tissue such as adipose and inactive muscle, will minimize glucose uptake by these tissues. Thus the glucose in the blood can be preferentially used by the active muscles where it's needed. Also, it is very important to realize that although insulin levels are decreasing during exercise by as much as 50%, blood flow to the active muscles can increase 10 to 15 fold. Thus, the active muscles actually see more insulin during exercise. As insulin promotes glucose uptake in muscle, this will enhance the exercising muscle's ability to extract glucose from the blood and use it for fuel. Lastly, exercise training results in a significant improvement in insulin sensitivity. This has major implications for the treatment of type 2 diabetes. 90 to 95% of all diabetics have type 2 diabetes which is primarily caused by an increase in insulin resistance. As we'll see in module four, there is no pill or technique more effective than regular exercise to improve insulin sensitivity for the treatment of type 2 diabetes. As shown here, the uptake of glucose from the blood during exercise can increase up to 20 fold when compared to rest. As usual, the extent of glucose uptake will be dependent upon the exercise intensity, insulin levels and muscle blood flow. The second hormone that plays a critical role in carbohydrate metabolism, and glucose homeostasis during exercise, is glucagon. Glucagon is produced and secreted by the alpha cells in the pancreas. Glucagon's primary function is to maintain blood glucose concentration when levels drop below normal as is the case during time between meals, fasting, and of course, during exercise. It accomplishes this functions by activating liver glycogen breakdown resulting in the release of the newly formed glucose into the blood. Glucagons during exercise is shown here, highlighted by the red arrows. At the onset of exercise, blood glucose levels drop below normal, as working muscles extract glucose from the blood for fuel. This decrease in blood glucose levels stimulates the release of glucagon from the pancreas. The elevation of glucagon levels in the blood, will activate glycogen breakdown in the liver, resulting in a release of glucose into the blood. As such, the working muscles will continue to have a source of glucose for fuel and eventual ATP production as long as liver glycogen stores hold out. This table demonstrates the metabolic effects of glucagon and glucose production and release by the liver. As can be seen glucagons primary function is to break down liver glycogen supplying free glucose to be released into the blood. However, a second role for glucagon is to stimulate gluconeogenesis in the liver. This pathway allows the liver to make glucose from non-carbohydrate precursors, such as amino acids and fats. This is particularly important during prolonged exercise, when liver glycogen stores are depleting. This gives an individual a non-carbohydrate source for glucose production to compensate for diminishing carbohydrate stores. Thus, during prolonged exercise, glucagon levels rise to increase glucose output by the liver to match glucose uptake by active skeletal muscles, thereby maintaining blood glucose concentrations. Notice that endurance trained individuals have a blunted glucagon response to exercise when compared to untrained individuals. This is the result of their greater ability to utilize fats and rely less on blood glucose. Thus, blood glucose levels will drop less in trained individuals, so there's less of a need for a glucagon response. In summary, insulin plays a major role in the significant increase in muscle glucose uptake during exercise. Glucagon plays a major role in maintaining blood glucose levels during exercise. Together, both insulin and glucagon ensure that working muscles have an adequate source of fuel for ATP production.