Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism

James R. Krycer, Katsuyuki Yugi, Akiyoshi Hirayama, Daniel J. Fazakerley, Lake Ee Quek, Richard Scalzo, Satoshi Ohno, Mark P. Hodson, Satsuki Ikeda, Futaba Shoji, Kumi Suzuki, Westa Domanova, Benjamin L. Parker, Marin E. Nelson, Sean J. Humphrey, Nigel Turner, Kyle L. Hoehn, Gregory J. Cooney, Tomoyoshi Soga, Shinya KurodaDavid E. James

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Insulin triggers an extensive signaling cascade to coordinate adipocyte glucose metabolism. It is considered that the major role of insulin is to provide anabolic substrates by activating GLUT4-dependent glucose uptake. However, insulin stimulates phosphorylation of many metabolic proteins. To examine the implications of this on glucose metabolism, we performed dynamic tracer metabolomics in cultured adipocytes treated with insulin. Temporal analysis of metabolite concentrations and tracer labeling revealed rapid and distinct changes in glucose metabolism, favoring specific glycolytic branch points and pyruvate anaplerosis. Integrating dynamic metabolomics and phosphoproteomics data revealed that insulin-dependent phosphorylation of anabolic enzymes occurred prior to substrate accumulation. Indeed, glycogen synthesis was activated independently of glucose supply. We refer to this phenomenon as metabolic priming, whereby insulin signaling creates a demand-driven system to “pull” glucose into specific anabolic pathways. This complements the supply-driven regulation of anabolism by substrate accumulation and highlights an additional role for insulin action in adipocyte glucose metabolism. Krycer et al. explore how insulin regulates adipocyte metabolism. It is widely held that energy storage (anabolism) occurs as a substrate accumulates. However, using dynamic tracer metabolomics and overlaying phosphoproteomics data, they find that insulin signaling triggers anabolism before substrates accumulate, creating a “demand-driven” system to prime adipocytes for glucose metabolism.

Original languageEnglish
Pages (from-to)3536-3547
Number of pages12
JournalCell Reports
Volume21
Issue number12
DOIs
Publication statusPublished - 2017 Dec 19

Keywords

  • adipocyte
  • glucose
  • insulin
  • metabolic priming
  • metabolic tracer
  • metabolomics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Krycer, J. R., Yugi, K., Hirayama, A., Fazakerley, D. J., Quek, L. E., Scalzo, R., Ohno, S., Hodson, M. P., Ikeda, S., Shoji, F., Suzuki, K., Domanova, W., Parker, B. L., Nelson, M. E., Humphrey, S. J., Turner, N., Hoehn, K. L., Cooney, G. J., Soga, T., ... James, D. E. (2017). Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism. Cell Reports, 21(12), 3536-3547. https://doi.org/10.1016/j.celrep.2017.11.085