Metabolism — What is the principal organ site for gluconeogenesis in humans under normal fasting conditions?

Introduction:
Maintaining euglycemia during fasting relies on hepatic glucose output, supplied initially by glycogenolysis and later by gluconeogenesis. This question asks you to identify the main organ responsible for gluconeogenesis in the normal physiological state.

Given Data / Assumptions:

• Liver contains the full gluconeogenic enzyme set including glucose-6-phosphatase.
• Kidney (renal cortex) can contribute significantly during prolonged fasting or acidosis but is usually secondary.
• Muscle lacks glucose-6-phosphatase and therefore cannot export free glucose to blood.

Concept / Approach:
Choose the organ with both pathway capacity and the ability to release glucose into circulation. Hepatic regulation by glucagon and cortisol upregulates gluconeogenic enzymes to sustain blood glucose for the brain and RBCs.

Step-by-Step Solution:

Verification / Alternative check:
Isotope tracer studies and clinical observation (hepatic failure → fasting hypoglycemia) verify the liver’s dominant role.

Why Other Options Are Wrong:

Common Pitfalls:
Overstating renal gluconeogenesis in early fasting; forgetting the role of glucose-6-phosphatase for export.

Final Answer:
Liver.