During hypoglycemia, plasma glucagon rises while insulin falls. Which additional counter-regulatory mechanism is MOST physiologically important in restoring blood glucose during PROLONGED (> 4 hours) hypoglycemia?
- A Epinephrine secretion stimulating glycogenolysis and inhibiting insulin release
- B Cortisol promoting gluconeogenesis from amino acids over 4-8 hours ✓
- C Growth hormone decreasing glucose uptake by peripheral tissues
- D Glucagon-stimulated hepatic glycogenolysis sustaining glucose for the full 4-hour period
Explanation
The counter-regulatory response to hypoglycemia is sequential: glucagon and epinephrine act within minutes (glycogenolysis, inhibit insulin), providing immediate glucose. However, glycogen stores are depleted within 4-8 hours. For sustained hypoglycemia, cortisol becomes the dominant counter-regulatory hormone, stimulating gluconeogenesis from amino acids (muscle protein catabolism), lipid mobilization, and reducing peripheral glucose utilization — actions that require hours to manifest but are critical for sustained glucose homeostasis. Growth hormone (option C) also contributes but is less potent than cortisol. Option D is incorrect as liver glycogen is exhausted by 4 hours.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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