The Source of Glycolytic Intermediates in Mammalian Tissues

Tara TeSlaa, Caroline R. Bartman, Connor S.R. Jankowski, Zhaoyue Zhang, Xincheng Xu, Xi Xing, Lin Wang, Wenyun Lu, Sheng Hui, Joshua D. Rabinowitz

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Glycolysis plays a central role in organismal metabolism, but its quantitative inputs across mammalian tissues remain unclear. Here we use 13C-tracing in mice to quantify glycolytic intermediate sources: circulating glucose, intra-tissue glycogen, and circulating gluconeogenic precursors. Circulating glucose is the main source of circulating lactate, the primary end product of tissue glycolysis. Yet circulating glucose highly labels glycolytic intermediates in only a few tissues: blood, spleen, diaphragm, and soleus muscle. Most glycolytic intermediates in the bulk of body tissue, including liver and quadriceps muscle, come instead from glycogen. Gluconeogenesis contributes less but also broadly to glycolytic intermediates, and its flux persists with physiologic feeding (but not hyperinsulinemic clamp). Instead of suppressing gluconeogenesis, feeding activates oxidation of circulating glucose and lactate to maintain glucose homeostasis. Thus, the bulk of the body slowly breaks down internally stored glycogen while select tissues rapidly catabolize circulating glucose to lactate for oxidation throughout the body.

Original languageEnglish (US)
Pages (from-to)367-378.e5
JournalCell Metabolism
Issue number2
StatePublished - Feb 2 2021

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Physiology
  • Cell Biology


  • compartmentalized metabolism
  • glucose homeostasis
  • glycogen
  • glycolysis
  • glycolytic intermediates
  • glycolytic specialist
  • isotope tracing
  • metabolic heterogeneity
  • red muscle


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