Cortisol Stimulates Gluconeogenesis in the Liver
Stress-induced cortisol primarily stimulates gluconeogenesis by affecting the liver (D). This process is a critical component of the body's stress response mechanism and plays an important role in maintaining blood glucose levels during periods of stress.
Mechanism of Cortisol Action on Gluconeogenesis
- Cortisol released during stress directly acts on the liver to stimulate endogenous glucose production through gluconeogenesis 1
- In the liver, cortisol promotes the conversion of non-carbohydrate substrates (such as amino acids, lactate, and glycerol) into glucose, increasing hepatic glucose output during stress 2
- Cortisol enhances the expression and activity of key gluconeogenic enzymes in the liver, which facilitates the conversion of precursors to glucose 3, 4
Physiological Pathway of Stress-Induced Hyperglycemia
- During stress, the release of stress hormones (including cortisol, glucagon, and catecholamines) leads to peripheral insulin resistance and increased hepatic glucose production 1
- Cortisol specifically increases hepatic glycogen supply and stimulates neoglucogenesis in the liver, contributing to stress hyperglycemia 1
- The stimulation of endogenous glucose production by cortisol in the liver is a key mechanism of stress hyperglycemia 1
Cortisol's Effects on Other Organs
- While cortisol affects multiple organs, its primary effect on gluconeogenesis occurs in the liver, not the anterior pituitary, pancreas, or adrenal cortex 4
- In skeletal muscle and adipose tissue, cortisol decreases glucose uptake and utilization by antagonizing insulin response, but these effects don't directly stimulate gluconeogenesis 4
- Cortisol works synergistically with other stress hormones like glucagon to enhance hepatic glucose output, but the direct stimulation of gluconeogenesis occurs in the liver 2, 5
Clinical Implications
- The cortisol-mediated increase in hepatic gluconeogenesis contributes to stress hyperglycemia observed in critically ill patients and during surgical procedures 1
- Prolonged cortisol elevation can lead to persistent insulin resistance and hyperglycemia, affecting patient outcomes in critical illness 1
- Understanding cortisol's effect on hepatic gluconeogenesis is important for managing stress-induced hyperglycemia in clinical settings 1
Molecular Mechanisms
- Cortisol binds to glucocorticoid receptors in hepatocytes, regulating the expression of genes involved in glucose metabolism 6
- This hormone-receptor complex upregulates transcription of enzymes critical for gluconeogenesis, including phosphoenolpyruvate carboxykinase and glucose-6-phosphatase 4
- Cortisol also increases the availability of gluconeogenic precursors to the liver by promoting protein catabolism in peripheral tissues 5