Renal Gluconeogenesis and Lactate Handling

Renal Gluconeogenesis

• The kidney can be considered as two separate organs: the proximal tubule produces glucose from non-carbohydrate precursors, while the medulla primarily utilizes glucose.
• Net arterio-venous glucose differences across the kidney can be misleading, as glucose consumption in the medulla can mask glucose release by the cortex.
• The kidney is a significant gluconeogenic organ in normal humans, accounting for up to 40% of whole-body gluconeogenesis in fasting individuals.
• Renal glucose release is increased in type 2 diabetes, similar to hepatic glucose release.

Lactate Handling in the Kidney

• Lactate can reach the nephron through filtration, blood flow, or production along the nephron.
• In the kidney, lactate can be oxidized to produce energy (consuming oxygen and generating ATP) or converted to glucose via gluconeogenesis (consuming oxygen and ATP).
• The kidney's ability to convert lactate to glucose participates in the Cori cycle (cell-cell lactate shuttle), which is important during vigorous exercise when oxidative phosphorylation is inhibited in muscle.

Cori Cycle (Cell-Cell Lactate Shuttle)

• In the Cori cycle, lactate produced in muscle is released into the blood and taken up by tissues capable of gluconeogenesis, such as the liver and kidney.
• In the proximal tubule, lactate is converted to glucose, which is then reabsorbed back into the blood for metabolism by the exercising muscle.
• The Cori cycle is an energy-requiring process that shifts the metabolic burden away from the exercising muscle during hypoxia.

Lactate Production in the Kidney

• Medullary lactate concentration is higher than in the cortex due to countercurrent arrangement of the vasa recta.
• Lactate production increases in the medulla during osmotic diuresis, possibly due to increased glycolysis driven by increased Na+ reabsorption.
• Distal nephron segments produce lactate through anaerobic glycolysis, especially during anoxia or when oxidative metabolism is inhibited.
• The IMCD (inner medullary collecting duct) has high levels of lactate production even under normal conditions, indicating it is primed for anaerobic glycolysis.

This quiz covers the process of renal gluconeogenesis, where the kidney produces glucose from non-carbohydrate precursors. It also explores lactate handling and glucose utilization in the kidney.