The plasma glucose concentration is maintained surprisingly constant during the fasting, or postabsorptive, state because of the secretion of glucose from the liver. This glucose is derived from the processes of glycogenolysis and gluconeogenesis, which are promoted by a high secretion of glucagon coupled with a low secretion of insulin.
Glucagon stimulates and insulin suppresses the hydrolysis of liver glycogen, or glycogenolysis. Thus during times of fasting, when glucagon secretion is high and insulin secretion is low, liver glycogen is used as a source of additional blood glucose. This results in the liberation of free glucose from glucose 6-phosphate by the action of an enzyme called glucose 6-phosphatase (chapter 5; see fig. 5.4). Only the liver has this enzyme, and therefore only the liver can use its stored glycogen as a source of additional blood glucose. Since muscles lack glucose 6-phosphatase, the glucose 6-phosphate produced from muscle glycogen can be used for glycolysis only by the muscle cells themselves.
Since there are only about 100 grams of stored glycogen in the liver, adequate blood glucose levels could not be maintained
614 Chapter Nineteen
Fasting (i insulin, T glucagon)
■ Figure 19.9 Catabolism during fasting. Increased glucagon secretion and decreased insulin secretion during fasting favors catabolism. These hormonal changes promote the release of glucose, fatty acids, ketone bodies, and amino acids into the blood. Notice that the liver secretes glucose that is derived both from the breakdown of liver glycogen and from the conversion of amino acids in gluconeogenesis.
for very long during fasting using this source alone. The low levels of insulin secretion during fasting, together with elevated glu-cagon secretion, however, promote gluconeogenesis, the formation of glucose from noncarbohydrate molecules. Low insulin allows the release of amino acids from skeletal muscles, while glucagon and cortisol (an adrenal hormone) stimulate the production of enzymes in the liver that convert amino acids to pyruvic acid and pyruvic acid into glucose. During prolonged fasting and exercise, gluconeogenesis in the liver using amino acids from muscles may be the only source of blood glucose.
The secretion of glucose from the liver during fasting compensates for the low blood glucose concentrations and helps to provide the brain with the glucose that it needs. But because insulin secretion is low during fasting, skeletal muscles cannot utilize blood glucose as an energy source. Instead, skeletal muscles—as well as the heart, liver, and kidneys—use free fatty acids as their major source of fuel. This helps to "spare" glucose for the brain.
The free fatty acids are made available by the action of glucagon. In the presence of low insulin levels, glucagon activates an enzyme in adipose cells called hormone-sensitive li-pase. This enzyme catalyzes the hydrolysis of stored triglycerides and the release of free fatty acids and glycerol into the blood. Glucagon also activates enzymes in the liver that convert some of these fatty acids into ketone bodies, which are secreted into the blood (fig. 19.9). Several organs in the body can use ketone bodies, as well as fatty acids, as a source of acetyl CoA in aerobic respiration.
Through the stimulation of lipolysis (the breakdown of fat) and ketogenesis (the formation of ketone bodies), the high glucagon and low insulin levels that occur during fasting provide circulating energy substrates for use by the muscles, liver, and other organs. Through liver glycogenolysis and gluconeo-genesis, these hormonal changes help to provide adequate levels of blood glucose to sustain the metabolism of the brain. The antagonistic action of insulin and glucagon (fig. 19.10) thus promotes appropriate metabolic responses during periods of fasting and periods of absorption.
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