From the Guidelines
The major substrate for hepatic gluconeogenesis during a marathon run is lactate. During prolonged exercise like marathon running, the liver maintains blood glucose levels through gluconeogenesis, with lactate serving as the primary precursor. As muscles work intensely, they produce lactate through anaerobic glycolysis, which is then transported to the liver via the bloodstream in what's known as the Cori cycle. The liver converts this lactate back into glucose, which returns to the bloodstream to fuel working muscles. While alanine (from muscle protein breakdown) and glycerol (from fat metabolism) also contribute to gluconeogenesis during extended exercise, lactate provides the largest contribution, accounting for approximately 60-70% of gluconeogenic substrates. This recycling process is crucial for endurance athletes as it helps maintain blood glucose levels when glycogen stores become depleted, typically after about 90 minutes of sustained exercise, allowing the marathon runner to continue performing despite diminishing energy reserves 1.
Key Points
- Lactate is the primary substrate for hepatic gluconeogenesis during marathon running
- The Cori cycle plays a crucial role in converting lactate back into glucose
- Lactate provides approximately 60-70% of gluconeogenic substrates during extended exercise
- Glycogen stores become depleted after about 90 minutes of sustained exercise, making gluconeogenesis crucial for maintaining blood glucose levels
Importance of Gluconeogenesis
Gluconeogenesis is essential for maintaining blood glucose levels during prolonged exercise, as it allows the liver to produce glucose from non-carbohydrate sources. This process is critical for endurance athletes, as it enables them to continue performing despite diminishing energy reserves. The liver's ability to convert lactate back into glucose through the Cori cycle is a key component of this process, and lactate provides the largest contribution to gluconeogenic substrates during extended exercise 1.
Clinical Implications
Understanding the role of lactate in hepatic gluconeogenesis during marathon running has important clinical implications for endurance athletes. By recognizing the importance of lactate as a substrate for gluconeogenesis, athletes and coaches can develop strategies to optimize glucose production and maintain blood glucose levels during prolonged exercise. This can include consuming carbohydrates during exercise, as well as incorporating training strategies that enhance the body's ability to utilize lactate as a fuel source 1.
From the Research
Major Substrate for Hepatic Gluconeogenesis
- Lactate is considered a major substrate for hepatic gluconeogenesis during exercise, as it is increased in the blood and can be converted to glucose in the liver 2.
- Glycerol is also a substrate for gluconeogenesis, but its importance is less than that of lactate 3, 2.
- Alanine and glutamine are glucogenic amino acids that can contribute to gluconeogenesis, but their role is more significant in certain physiological and pathological conditions, such as starvation, diabetes, and liver cirrhosis 4.
- Pyruvate is a major gluconeogenic substrate that requires import into the mitochondrial matrix for channeling into gluconeogenesis, and the mitochondrial pyruvate carrier (MPC) is required for efficient regulation of hepatic gluconeogenesis 5.
Substrate Utilization During Exercise
- During exercise, the liver increases glucose production through gluconeogenesis, and lactate is a major precursor for this process 6, 2.
- The importance of precursor supply to maintain basal glucose production is confirmed by the response to dichloroacetate (DCA), which decreases the fluxes of pyruvate, alanine, and lactate, and reduces glucose production 3.
- Endurance training increases the ability to achieve a higher relative exercise intensity and absolute power output at the lactate threshold without a significant decrease in gluconeogenesis 6.