Effects of Cortisol on Carbohydrate Metabolism

Effects of Cortisol on Carbohydrate Metabolism

Stimulation of Gluconeogenesis. By far the best-knownmetabolic effect of cortisol and other glucocorticoids on metabolism is their ability to stimulate gluconeo-genesis (formation of carbohydrate from proteins and some other substances) by the liver, often increasing the rate of gluconeogenesis as much as 6- to 10-fold. This results mainly from two effects of cortisol.

1. Cortisol increases the enzymes required to convert amino acids into glucose in the liver cells. Thisresults from the effect of the glucocorticoids to activate DNA transcription in the liver cell nuclei in the same way that aldosterone functions in the renal tubular cells, with formation of messenger RNAs that in turn lead to the array of enzymes required for gluconeogenesis.

2. Cortisol causes mobilization of amino acids from the extrahepatic tissues mainly from muscle. As aresult, more amino acids become available in the plasma to enter into the gluconeogenesis process of the liver and thereby to promote the formation of glucose.

One of the effects of increased gluconeogenesis is a marked increase in glycogen storage in the liver cells. This effect of cortisol allows other glycolytic hor-mones, such as epinephrine and glucagon, to mobilize glucose in times of need, such as between meals.

Decreased Glucose Utilization by Cells. Cortisol also causesa moderate decrease in the rate of glucose utilization by most cells in the body. Although the cause of this decrease is unknown, most physiologists believe that somewhere between the point of entry of glucose into the cells and its final degradation, cortisol directly delays the rate of glucose utilization. A suggested mechanism is based on the observation that glucocor-ticoids depress the oxidation of nicotinamide-adenine dinucleotide (NADH) to form NAD⁺. Because NADH must be oxidized to allow glycolysis, this effect could account for the diminished utilization of glucose by the cells.

Elevated Blood Glucose Concentration and “Adrenal Diabetes.”

Both the increased rate of gluconeogenesis and the moderate reduction in the rate of glucose utilization by the cells cause the blood glucose concentrations to rise. The rise in blood glucose in turn stimulates secretion of insulin. The increased plasma levels of insulin, however, are not as effective in maintaining plasma glucose as they are under normal conditions. For reasons that are not entirely clear, high levels of glucocorticoid reduce the sensitivity of many tissues, especially skeletal muscle and adipose tissue, to the stimulatory effects of insulin on glucose uptake and utilization. One possible explanation is that high levels of fatty acids, caused by the effect of glucocor-ticoids to mobilize lipids from fat depots, may impair insulin’s actions on the tissues. In this way, excess secretion of glucocorticoids may produce disturbances of carbohydrate metabolism very similar to those found in patients with excess levels of growth hormone.

The increase in blood glucose concentration is occa-sionally great enough (50 per cent or more above normal) that the condition is called adrenal diabetes. Administration of insulin lowers the blood glucose concentration only a moderate amount in adrenal diabetes-not nearly as much as it does in pancreatic diabetes-because the tissues are resistant to the effects of insulin.