[PDF][PDF] The source of glycolytic intermediates in mammalian tissues

T TeSlaa, CR Bartman, CSR Jankowski, Z Zhang, X Xu… - Cell metabolism, 2021 - cell.com
Cell metabolism, 2021cell.com
Glycolysis plays a central role in organismal metabolism, but its quantitative inputs across
mammalian tissues remain unclear. Here we use 13 C-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 …
Summary
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.
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