Which hormone promotes gluconeogenesis?

• A. Growth hormone
• B. Hydrocortisone
• C. Insulin
• D. Thyroxine

Answer: (B)

During fasting or stress, the liver increases glucose production to keep blood sugar steady. The hormone that most directly promotes gluconeogenesis among these options is hydrocortisone, the glucocorticoid cortisol. Cortisol acts on the liver to upregulate the enzymes responsible for gluconeogenesis, such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, boosting the synthesis of glucose from noncarbohydrate substrates. It also enhances substrate availability by promoting protein breakdown to release amino acids and fat breakdown to provide glycerol and energy, and it tends to reduce peripheral glucose uptake to spare glucose for essential tissues. Growth hormone can raise glucose levels somewhat by increasing lipolysis and insulin resistance, but its effect on the specific gluconeogenic pathway is less direct. Insulin inhibits gluconeogenesis, and thyroxine mainly increases overall metabolic rate rather than directly driving gluconeogenesis. Hence, cortisol (hydrocortisone) best promotes gluconeogenesis.