Metabolic

The concentration of glucose in the blood, set within the normal adult range of 3.9 to 5.8 mmol/L (70-105 mg/100 mL), is probably the most regulated of all substances. When a carbohydrate meal is ingested, the level may temporarily rise to 6.5 to 7.2 mmol/L, and during fasting it can fall to 3.3 to 3.9 mmol/L. One of the major reasons for closely regulating blood glucose levels is that the brain normally depends on a continuous supply, although it can adapt to lower levels or even use ketone bodies from fat breakdown (27) if adaptation occurs slowly. This becomes essential during starvation, since the adult human brain uses about 140 g/day of glucose (28), and only about 130 g/day of glucose can be obtained from noncarbohydrate sources. Injection of a hormone, such as insulin, that rapidly lowers the blood glucose level can lead to convulsions and even death if left uncorrected.

Glucose enters the blood pool (about 16 g) from a number of sources. In normal postabsorptive man, the plasma appearance rate is 8 to 10 g/h, the blood pool being replaced every 2 hours. At normal blood glucose levels, the liver is a net producer of glucose.

When the dietary carbohydrates in a meal are finally hydrolyzed to glucose, galactose, and fructose, after absorption these are transported by the portal blood flow into the liver and kidney. The rising level of glucose to the liver decreases the liver output of glucose. In the rat, uptake and output are equal at about 8.3 mmol/L. The glucose entering the blood during a meal is handled by the liver and peripheral tissues, the first step being phosphorylation. In the tissues, phosphorylation is by hexokinase, an enzyme subject to feedback inhibition by the product, glucose-6-phosphate. The liver enzyme, glucokinase, is not so affected, has a lower affinity for glucose, and can increase its activity over the normal range of glucose found in the portal blood. It thus appears to be ideal for handling the high levels of glucose that enter the portal blood during a carbohydrate meal. Both galactose and fructose can be converted into glucose by the hepatic cells, so little of either hexose is found in the peripheral circulation, and more than 95% of all circulating hexoses is glucose.

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