Which hormone does not increase plasma glucose concentration by converting glycogen to glucose: Epinephrine (adrenaline), Glucagon, or Cortisol?

Which Hormone Does NOT Increase Plasma Glucose by Converting Glycogen to Glucose

Cortisol does NOT increase plasma glucose concentration by converting glycogen to glucose, unlike epinephrine and glucagon which directly stimulate glycogenolysis in the liver.

Mechanism of Action of Each Hormone

Epinephrine

• Directly activates glycogenolysis (glycogen breakdown) in the liver through β-adrenergic receptors
• Rapidly increases blood glucose levels within minutes of secretion
• According to FDA information, epinephrine has immediate effects on hepatic glycogen stores, stimulating their breakdown and release of glucose 1

Glucagon

• Primary hormone for glycogenolysis during fasting states
• Acts by binding to hepatic glucagon receptors, directly stimulating glycogen breakdown
• FDA drug information states: "Glucagon increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Hepatic stores of glycogen are necessary for glucagon to produce an antihypoglycemic effect" 1
• Blood glucose rises within 10 minutes of glucagon injection with maximal effect at approximately 30 minutes 1

Cortisol

• Does NOT directly stimulate glycogenolysis (glycogen breakdown)
• Instead, cortisol primarily increases blood glucose through:
  1. Stimulating gluconeogenesis (formation of new glucose from non-carbohydrate sources)
  2. Decreasing peripheral glucose utilization
  3. Increasing insulin resistance
• According to the Endocrine Society, cortisol increases blood sugar levels primarily by stimulating gluconeogenesis, not glycogenolysis 2

Physiological Evidence

The Diabetes Care guidelines note that several hormones, including "growth hormone, cortisol, glucagon, epinephrine antagonize insulin action" 3. However, only glucagon and epinephrine are known to directly activate glycogenolysis.

Research studies have demonstrated that:

• Cortisol's effect on glucose metabolism is primarily through enhancing gluconeogenesis rather than glycogenolysis 4
• When cortisol is absent during stress hormone infusion, hepatic glycogen becomes depleted, indicating cortisol's role in preserving glycogen rather than breaking it down 5
• Epinephrine and glucagon act rapidly on glycogen stores, while cortisol has a delayed effect on glucose metabolism 6

Clinical Implications

Understanding these hormonal differences is important in clinical settings:

• In stress hyperglycemia, epinephrine and glucagon provide immediate glucose elevation through glycogenolysis
• Cortisol sustains hyperglycemia through gluconeogenesis and insulin resistance
• In patients receiving glucocorticoid therapy, hyperglycemia occurs primarily through increased gluconeogenesis and insulin resistance, not glycogenolysis 3

In conclusion, while all three hormones (epinephrine, glucagon, and cortisol) can increase plasma glucose concentration, cortisol is the only one that does not do so primarily through converting glycogen to glucose (glycogenolysis).