The Source of Glycolytic Intermediates in Mammalian Tissues.

TitleThe Source of Glycolytic Intermediates in Mammalian Tissues.
Publication TypeJournal Article
Year of Publication2021
AuthorsTeSlaa, T, Bartman, CR, Jankowski, CSR, Zhang, Z, Xu, X, Xing, X, Wang, L, Lu, W, Hui, S, Rabinowitz, JD
JournalCell Metab
Date Published2021 Feb 02
KeywordsAnimals, Blood Glucose, Carbon Isotopes, Diaphragm, Gluconeogenesis, Glycogen, Glycolysis, Male, Mice, Mice, Inbred C57BL, Muscle, Skeletal, Spleen

<p>Glycolysis plays a central role in organismal metabolism, but its quantitative inputs across mammalian tissues remain unclear. Here we use 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 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.</p>

Alternate JournalCell Metab
PubMed ID33472024
PubMed Central IDPMC8088818
Grant ListDP1 DK113643 / DK / NIDDK NIH HHS / United States
F32 DK118856 / DK / NIDDK NIH HHS / United States
P30 DK019525 / DK / NIDDK NIH HHS / United States
R00 DK117066 / DK / NIDDK NIH HHS / United States