Sites of gluconeogenesis
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Here is a complete summary of the sites of gluconeogenesis, drawn from authoritative textbooks:
Sites of Gluconeogenesis
1. Liver (Primary Site)
- Responsible for ~90% of gluconeogenesis during an overnight fast
- Contains the full complement of gluconeogenic enzymes in both the mitochondria and cytosol
- Releases glucose into the portal circulation to maintain blood glucose levels for glucose-dependent tissues (brain, RBCs, kidney medulla, lens, cornea, testes, exercising muscle)
- Uses all major gluconeogenic precursors: lactate (via the Cori cycle), glycerol, and glucogenic amino acids
2. Kidney (Secondary Site - Cortex Only)
- Contributes ~10% of gluconeogenesis after an overnight fast
- During prolonged fasting (48+ hours), the kidneys become major glucose-producing organs, contributing up to ~40% of total glucose production
- In type 2 diabetes, renal gluconeogenesis is pathologically increased
- Gluconeogenesis occurs exclusively in the proximal tubule (cortex); the medulla primarily consumes glucose
- Evidence: during liver transplantation (after liver removal), endogenous glucose release falls to only ~50% of control, confirming substantial kidney contribution
- Key substrates used: lactate, glutamine (a major renal gluconeogenic precursor)
3. Small Intestine (Minor Site)
- Can synthesize glucose, but its contribution is minor under normal conditions
- More relevant in the context of intestinal glucose homeostasis research
Tissues That CANNOT Perform Gluconeogenesis
| Tissue | Reason |
|---|---|
| Brain | Lacks key enzymes (glucose-6-phosphatase, etc.) |
| Skeletal muscle | Lacks glucose-6-phosphatase; cannot export free glucose |
| Red blood cells | No mitochondria; lack gluconeogenic enzymes |
| Adipose tissue | Lacks the necessary enzyme set |
Summary by Fasting State
| State | Liver | Kidney | Intestine |
|---|---|---|---|
| Post-meal / short fast | ~90% | ~10% | Minor |
| Prolonged fast (>48 h) | ~60% | ~40% | Minor |
Sources: Lippincott Illustrated Reviews: Biochemistry, 8e, p. 353 | Basic Medical Biochemistry, 6e, p. 1007 | Brenner and Rector's The Kidney, p. 217
Where does gluconeogenesis occursvin kidney
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Here is a detailed answer based directly from Brenner & Rector's The Kidney:
Gluconeogenesis in the Kidney: Exact Location
Primary Site: Proximal Tubule (Renal Cortex)
Gluconeogenesis occurs along the entire proximal tubule, but activity is highest in the earlier segments (S1 > S2 > S3). The kidney can be thought of as two functionally separate organs:
- Renal cortex (proximal tubule) - produces glucose via gluconeogenesis
- Renal medulla - primarily consumes glucose (glycolysis)
This is why simple arterio-venous glucose differences across the whole kidney can be misleading - medullary glucose consumption can mask cortical glucose release.
Proximal Tubule Segments and Their Roles
| Segment | Role | Primary Substrate |
|---|---|---|
| S1 | Highest gluconeogenic activity; major site during metabolic acidosis | Lactate, glutamine |
| S2 | Active gluconeogenesis; lactate preferred over glutamine | Lactate > glutamine |
| S3 | Gluconeogenesis present; glucose may enter intrarenal Cori cycle | Lactate |
Key Points
- Starvation stimulates gluconeogenesis uniformly along the entire proximal tubule
- Metabolic acidosis specifically enhances gluconeogenesis in S1 and S2 segments, using glutamine as the primary substrate
- During glutamine-driven gluconeogenesis, ammonium (NH4+) is produced and excreted in urine as an acid equivalent, while new bicarbonate is generated - this is why acidosis is a strong stimulus for renal gluconeogenesis
- The healthy human kidney produces 15-55 g of glucose per day by gluconeogenesis
- In the postabsorptive state (12-16 hours after a meal), liver and kidneys contribute roughly equal amounts of glucose via gluconeogenesis
Regulators of Renal Gluconeogenesis
| Factor | Effect |
|---|---|
| Epinephrine | Stimulates |
| Insulin | Inhibits (via FoxO1 phosphorylation) |
| Glucagon | No significant effect (unlike the liver) |
| Metabolic acidosis | Strong stimulator (S1/S2) |
| SGLT2 inhibitors | May indirectly upregulate gluconeogenic gene expression |
Source: Brenner and Rector's The Kidney, p. 217 & RENAL FORMATION OF GLUCOSE section
But Lippincott illustrated bipchemistry says that gluconeogenesis occurs in renal medulla
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This is a great question to clarify. After checking the actual Lippincott text directly, here is what is really happening:
What Lippincott Actually Says
Lippincott Illustrated Reviews: Biochemistry (8e) does not say gluconeogenesis occurs in the renal medulla. What it says is:
"Some tissues, such as the brain, erythrocytes, kidney medulla, lens and cornea of the eye, testes, and exercising skeletal muscle, require a continuous supply of glucose as a metabolic fuel."
The kidney medulla is listed as a glucose consumer, not a glucose producer. This is consistent with what Brenner & Rector says.
The Correct Picture (All Sources Agree)
| Kidney Zone | Role in Glucose Metabolism |
|---|---|
| Renal cortex (proximal tubule) | Produces glucose via gluconeogenesis |
| Renal medulla | Consumes glucose (depends on glycolysis) |
This is precisely why the kidney is not always a net exporter of glucose - the medulla's consumption can offset the cortex's production.
Harper's Illustrated Biochemistry (32e) states this explicitly:
"While the renal cortex may contribute ~10% of whole-body gluconeogenesis after a short-term fast, the kidney is not a net source of glucose, because the renal medulla is a consumer of glucose."
Basic Medical Biochemistry (6e) also confirms:
"The glucose produced by the kidney cortex is used by the kidney medulla, but some may enter the bloodstream."
Summary
The likely source of confusion is that Lippincott mentions the kidney medulla in the context of gluconeogenesis - but as a tissue that requires glucose, not one that produces it. Gluconeogenesis in the kidney is firmly localized to the renal cortex, specifically the proximal tubule (S1 > S2 > S3 segments).
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See this it says gluconeogenesis occurs in renal medulla
analyse_media
Finding Sources
I can read the image clearly. The sentence reads:
"Apart from the liver, renal medulla is also a site for gluconeogenesis."
This is an important discrepancy between sources, and here is how to understand it honestly:
Is This Statement Correct?
This statement is inaccurate according to the weight of evidence. Here is why:
What the Authoritative Sources Say
| Source | What it states |
|---|---|
| Lippincott Illustrated Reviews: Biochemistry 8e | Kidney medulla is a glucose consumer, not a producer |
| Harper's Illustrated Biochemistry 32e | "Renal cortex contributes ~10% of gluconeogenesis; the kidney is NOT a net glucose source because the medulla consumes glucose" |
| Basic Medical Biochemistry 6e | "Glucose produced by kidney cortex is used by the kidney medulla" |
| Brenner & Rector's The Kidney | Gluconeogenesis occurs in the proximal tubule (cortex); medulla primarily does glycolysis |
Why the Medulla Cannot Do Gluconeogenesis
The renal medulla operates in a relatively hypoxic environment and relies on anaerobic glycolysis for energy. It:
- Lacks the key gluconeogenic enzymes (especially glucose-6-phosphatase and PEPCK)
- Actively consumes glucose
- Produces lactate, which is then shuttled to the cortex for gluconeogenesis
What This Book Likely Is
The image appears to be from a physiology review/notes book (not a primary biochemistry reference). Such books sometimes carry oversimplified or outright incorrect statements. The sentence "renal medulla is a site for gluconeogenesis" contradicts all major biochemistry textbooks.
The Correct Statement
Gluconeogenesis in the kidney occurs in the renal cortex, specifically the proximal tubule. The renal medulla is a site of glycolysis and glucose consumption, not gluconeogenesis.
For exams based on Lippincott, Harper's, or Lehninger - go with renal cortex (proximal tubule). If your exam is based on this particular book, flag it as a known error in the source material.
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