From the Research
Alanine is the primary substrate from skeletal muscle that supports hepatic gluconeogenesis, as evidenced by the most recent and highest quality study 1.
Key Points
- During periods of fasting or exercise, skeletal muscle releases alanine into the bloodstream, which is then taken up by the liver.
- In the liver, alanine is converted to pyruvate through a process called transamination, and this pyruvate serves as a precursor for glucose production via gluconeogenesis.
- This metabolic pathway, known as the glucose-alanine cycle, is crucial for maintaining blood glucose levels during periods of energy demand.
- Skeletal muscle produces alanine through the transamination of pyruvate, using amino groups from branched-chain amino acids.
- Other amino acids like glutamine are also released from muscle and can contribute to gluconeogenesis, but alanine is quantitatively the most significant amino acid substrate in this inter-organ metabolic cooperation, as supported by studies 2, 1.
Mechanism of Action
- The glucose-alanine cycle is a critical mechanism for maintaining glucose homeostasis, particularly during periods of fasting or exercise.
- Alanine is produced in skeletal muscle through the transamination of pyruvate, and then transported to the liver where it is converted to glucose via gluconeogenesis.
- This process not only provides substrate for hepatic glucose production but also serves as a mechanism for transporting nitrogen from muscle to the liver for eventual excretion as urea.
Clinical Implications
- Understanding the role of alanine in hepatic gluconeogenesis has important implications for the management of glucose metabolism in various clinical contexts, such as diabetes and sepsis.
- The maintenance of gluconeogenesis from glycerol, but not from alanine, lactate, and pyruvate, in liver perfusion of rats with early and late sepsis, highlights the potential importance of glycerol as a precursor for glucose production in certain clinical scenarios 3.