![]() ![]() Blood glucose is protected by liver gluconeogenesis after glycogen stores become critically low. The amount of glucose in the blood can still be constant after 2 h of exercise in well-nourished subjects. Muscle glycogen breakdown impedes the removal of glucose from the blood by increasing glucose 6-phosphate (G6P), which inhibits the hexokinase (HK) reaction, and by providing a source of fuel that diminishes the need for blood glucose. Liver glycogen breakdown protects blood glucose as the glucose moieties that comprise it are released into the blood. Blood glucose is preserved at the expense of liver and muscle glycogen. Carbohydrate oxidation by the working muscle can go up by ∼10-fold with exercise, and yet after 1 h, blood glucose is maintained at ∼4 g. In postabsorptive humans, there are ∼100 g of glycogen in the liver and ∼400 g of glycogen in muscle. The amount of glucose in the blood is preserved at the expense of glycogen reservoirs ( Fig. If glucose production does not increase, as sometimes happens in diabetics treated with too much insulin, hypoglycemia ensues. The liver is stimulated to produce glucose, again minimizing deviations in blood glucose. Insulin-independent mechanisms are activated that increase muscle glucose uptake during exercise. The result is that deviations in blood glucose are dampened. Insulin suppresses the entry of glucose from liver to blood and stimulates glucose removal from blood in to muscle, liver, and fat. Ingestion of a meal high in carbohydrates causes an incretin response and increased β-cell insulin secretion. The real test of glucoregulation comes when it is challenged. Although the kidney can make glucose, it is a minor source compared with the liver. ![]() The liver releases glucose formed by glycogenolysis and gluconeogenesis into the blood at rates equal to the uptake of blood glucose. ![]() The brain consumes ∼60% of the blood glucose used in the sedentary, fasted person. Glucose is extracted from the blood to sustain metabolism in a variety of tissues. Organs can exert effects by direct control of glucose flux (black lines) or indirectly by humoral and neural signals (blue lines). Understanding factors that protect blood glucose and maintain glucose homeostasis requires the communication between organs and integration of signals that is evident in in vivo model systems. Much has been learned and remains to be learned about glucose metabolism by assessing organs, tissues, and cells independently. Lines of communication form a complex network. This level of control requires an in vivo model system to be fully delineated. Communication can be by modification of glucose flux directly or through humoral and neural signaling mechanisms ( Fig. The components essential to regulation of blood glucose communicate with each other. However, glucose homeostasis requires integrated control by the whole organism. Experiments in isolated organs, tissues, and cells have contributed extensively to our understanding of this control system. In accordance with the importance of blood glucose, a sophisticated control system is in place to protect it from marked deviations. It summarizes research conducted in our laboratory at Vanderbilt University that has examined the regulation of blood glucose homeostasis. ![]() Berson Lecture presented at Experimental Biology 2008. A persistent elevation in blood glucose leads to “glucose toxicity.” Glucose toxicity contributes to β-cell dysfunction and the pathology grouped together as complications of diabetes. A serious fall in blood glucose can be characterized by metabolic dysfunction, neuroglycopenia, seizure, and death. Although these 4 g constitute an infinitesimally small fraction of the mass of the total organism, a wide variety of cells rely on it and are sensitive to its presence. This is the amount needed to fill a teaspoon. Four grams of glucose circulates in the blood of a person weighing 70 kg. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |