Cortisol Stimulates Gluconeogenesis in the Liver
Stress-induced cortisol directly stimulates gluconeogenesis in the liver, leading to increased endogenous glucose production. 1
Mechanism of Cortisol Action on Gluconeogenesis
- Cortisol released during stress acts specifically on hepatic tissues to upregulate both gluconeogenesis and glycogenolysis, even when serum insulin levels (which normally suppress these pathways) are high 2
- During stress response, cortisol directly stimulates the liver to increase endogenous glucose production through enhanced gluconeogenic enzyme activity 1, 3
- Cortisol plays a pivotal role in maintaining hepatic glycogen availability while simultaneously enhancing gluconeogenesis, creating a dual mechanism for increasing blood glucose during stress 4
Physiological Pathway of Stress-Induced Hyperglycemia
- The stress imposed by critical illness triggers metabolic and endocrine abnormalities, with cortisol being one of the key hormones that stimulate hepatic glucose production 2
- Stress-induced cortisol release leads to peripheral insulin resistance and simultaneously increases hepatic glucose output, contributing to what is known as "stress diabetes" or "diabetes of injury" 2
- Cortisol specifically targets the liver to increase glycogen supply and stimulate neoglucogenesis, resulting in elevated blood glucose levels during stress 1
Evidence from Research Studies
- Studies demonstrate that cortisol's absence during stress hormone infusion significantly attenuates the increase in plasma glucose concentration and overall glucose production, confirming its critical role in stress-induced hyperglycemia 4
- Cortisol augments glucagon-stimulated gluconeogenesis in an additive manner, primarily through changes in gluconeogenic enzymes rather than substrate availability 5
- Research shows that cortisol directly stimulates net glyconeogenesis approximately 2-fold after a short lag period, increasing both glucose production and glycogen formation in liver tissue 6
Clinical Implications
- Understanding cortisol's effect on hepatic gluconeogenesis is crucial for managing stress-induced hyperglycemia in clinical settings, particularly in critically ill patients 1
- Prolonged cortisol elevation leads to persistent insulin resistance and hyperglycemia, which can adversely affect patient outcomes in critical illness 1, 3
- The cortisol-mediated increase in hepatic glucose production contributes significantly to the hyperglycemia observed during physical and psychological stress, requiring appropriate management strategies 2
Common Pitfalls in Understanding Cortisol's Action
- A common misconception is attributing stress-induced hyperglycemia solely to pancreatic effects or anterior pituitary stimulation, when the primary target for cortisol's gluconeogenic effect is the liver 1, 3
- While cortisol is produced by the adrenal cortex, it does not primarily act on this structure to stimulate gluconeogenesis, but rather targets hepatic tissues 2
- Although cortisol can affect pancreatic function, its direct stimulation of hepatic gluconeogenesis is the predominant mechanism for increasing blood glucose during stress 3