From the Guidelines
No, the kidneys do not produce most endogenous glucose, with the liver being the primary organ responsible for glucose production, accounting for approximately 80% of endogenous glucose production under normal conditions. The kidneys contribute about 20% to 25% of blood glucose via gluconeogenesis during prolonged fasting states, as noted in a study published in Endocrine Reviews in 2020 1. This study highlights the complex interplay between the kidney, glucose, and insulin, with the kidney's role in glucose production becoming more significant during prolonged fasting or starvation states.
The liver produces glucose through two main pathways: glycogenolysis (breakdown of stored glycogen) and gluconeogenesis (synthesis of new glucose from precursors like amino acids, lactate, and glycerol) 2. While the kidneys also possess gluconeogenic enzymes and can synthesize glucose, their contribution is significantly less than the liver's under normal physiological conditions. The renal contribution to glucose production becomes more important during prolonged fasting when liver glycogen stores are depleted, or in certain disease states like diabetes.
Key points to consider:
- The liver is the primary organ responsible for glucose production, accounting for approximately 80% of endogenous glucose production under normal conditions.
- The kidneys contribute about 20% to 25% of blood glucose via gluconeogenesis during prolonged fasting states.
- The kidney's role in glucose production becomes more significant during prolonged fasting or starvation states.
- The division of labor between the liver and kidneys helps maintain blood glucose levels within the normal range, which is essential for proper functioning of the brain and other glucose-dependent tissues, as supported by the study published in Endocrine Reviews in 2020 1, 2.
From the Research
Kidney's Role in Glucose Production
- The kidneys play a significant role in glucose homeostasis via gluconeogenesis, glucose utilization, and glucose reabsorption from the renal glomerular filtrate 3.
- After an overnight fast, 20-25% of glucose released into the circulation originates from the kidneys through gluconeogenesis 3.
- In the postprandial period, renal gluconeogenesis increases and accounts for approximately 60% of endogenous glucose release 3.
Comparison with the Liver
- Both the liver and kidneys express the key enzymes necessary for endogenous glucose production and its export into circulation 4.
- The liver is, in most instances, the primary bulk contributor to systemic glucose due to its size, but the kidney's contribution to endogenous glucose production is often under-appreciated 4.
- The human liver and kidneys release approximately equal amounts of glucose via gluconeogenesis in the postabsorptive state 5.
Renal Gluconeogenesis
- Renal glucose release is almost exclusively due to gluconeogenesis, which occurs in the proximal tubule cells 4, 5.
- The kidney accounts for ∼40% of endogenous gluconeogenesis during the post-absorptive phase, with lactate as the main substrate 6.
- Renal gluconeogenesis is regulated by insulin, cellular glucose levels, acidosis, and stress hormones 6.
Clinical Relevance
- The impact of acute and chronic kidney disease and proximal tubular injury on gluconeogenesis is not well studied, but recent evidence shows that impaired renal gluconeogenesis could significantly participate in systemic metabolic disturbance 6.
- Patients with type 2 diabetes have an increased renal glucose uptake and release in the fasting and post-prandial states 3, 5.
- The kidney's role in glucose metabolism is a focus of research, with the success of inhibitors in reducing kidney and cardiovascular diseases in individuals with diabetes 7.