# Gluconeogenesis

Gluconeogenesis is how your liver (and, in long fasts, your kidney) makes new glucose from non-carb sources. The main precursors are lactate, glycerol, and 'glucogenic' amino acids like alanine and glutamine. The pathway mostly runs glycolysis in reverse, but it bypasses glycolysis's three one-way steps using four specific enzymes: pyruvate carboxylase, PEPCK, fructose-1,6-bisphosphatase, and glucose-6-phosphatase. Glucagon and cortisol switch it on; insulin shuts it off. In a healthy adult fasting overnight, gluconeogenesis makes up about 50% of the liver's glucose output. That rises to about 93% after 42 hours, once glycogen stores run out (Landau et al., 1996). This is why your blood glucose stays in the normal range on a ketogenic diet or a long fast, sustained by glycerol from fat and alanine from muscle, even with no dietary carbs. In aging research, boosting one of these enzymes (PEPCK) in the gut cells of the worm C. elegans extends lifespan under dietary restriction, and blocking it cancels that benefit (Onken et al., 2020, PLoS Genetics). Whether that mechanism carries over to mammals is still associational, not proven.

## Sources

- Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC. (1996). Contributions of gluconeogenesis to glucose production in the fasted state. Journal of Clinical Investigation. https://doi.org/10.1172/jci118803
- Onken B, Kalinava N, Driscoll M. (2020). Gluconeogenesis and PEPCK are critical components of healthy aging and dietary restriction life extension. PLOS Genetics. https://doi.org/10.1371/journal.pgen.1008982
- Sahoo B, Srivastava M, Katiyar A, Ecelbarger C, Tiwari S. (2023). Liver or kidney: Who has the oar in the gluconeogenesis boat and when?. World Journal of Diabetes. https://doi.org/10.4239/wjd.v14.i7.1049

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_Canonical: https://longevity-switzerland.com/en/glossary/gluconeogenesis · Part of Longevity Cities · Updated 2026-06-22_