Krycer, James R. and Yugi, Katsuyuki and Hirayama, Akiyoshi and Fazakerley, Daniel J. and Quek, Lake-Ee and Scalzo, Richard and Ohno, Satoshi and Hodson, Mark P and Ikeda, Satsuki and Shoji, Futaba and Suzuki, Kumi and Domanova, Westa and Parker, Benjamin L. and Nelson, Marin E. and Humphrey, Sean J. and Turner, Nigel and Hoehn, Kyle L. and Cooney, Gregory J. and Soga, Tomoyoshi and Kuroda, Shinya and James, David E. (2017) Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism. Cell Reports, 21 (12). pp.3536-3547. ISSN 22111247 (Gold OA)
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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.
| Item Type: | Article |
|---|---|
| Keywords: | Victor Chang Innovation Centre |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 01 Jan 2018 22:26 |
| Last Modified: | 17 Jun 2018 23:48 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/679 |
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