Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism
Summary: 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....
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| Format: | Article |
| Language: | English |
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Elsevier
2017-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717317527 |
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doaj-193162bf744244048cb268ff37395957 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 Kuroda David E. James |
| spellingShingle |
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 Kuroda David E. James Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism Cell Reports |
| author_facet |
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 Kuroda David E. James |
| author_sort |
James R. Krycer |
| title |
Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism |
| title_short |
Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism |
| title_full |
Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism |
| title_fullStr |
Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism |
| title_full_unstemmed |
Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism |
| title_sort |
dynamic metabolomics reveals that insulin primes the adipocyte for glucose metabolism |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2017-12-01 |
| description |
Summary: 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. Keywords: adipocyte, insulin, glucose, metabolomics, metabolic tracer, metabolic priming |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124717317527 |
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1725080740945723392 |
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doaj-193162bf744244048cb268ff373959572020-11-25T01:32:39ZengElsevierCell Reports2211-12472017-12-01211235363547Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose MetabolismJames R. Krycer0Katsuyuki Yugi1Akiyoshi Hirayama2Daniel J. Fazakerley3Lake-Ee Quek4Richard Scalzo5Satoshi Ohno6Mark P. Hodson7Satsuki Ikeda8Futaba Shoji9Kumi Suzuki10Westa Domanova11Benjamin L. Parker12Marin E. Nelson13Sean J. Humphrey14Nigel Turner15Kyle L. Hoehn16Gregory J. Cooney17Tomoyoshi Soga18Shinya Kuroda19David E. James20School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan; YCI Laboratory for Trans-Omics, Young Chief Investigator Program, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; PRESTO, Japan Science and Technology Agency, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan; AMED-CREST, AMED, 1-7-1 Otemachi, Chiyoda-Ku, Tokyo 100-0004, JapanSchool of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, AustraliaCharles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia; School of Mathematics and Statistics, The University of Sydney, Sydney NSW 2006, AustraliaCentre for Translational Data Science, University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanMetabolomics Australia Queensland Node, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, QLD 4072, Australia; School of Pharmacy, Faculty of Health and Behavioural Sciences, University of Queensland, Brisbane, QLD 4072, Australia; Metabolomics Research Laboratory, Victor Chang Innovation Centre, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, AustraliaInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanCharles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia; School of Physics, University of Sydney, Sydney, NSW 2006, AustraliaSchool of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, AustraliaSchool of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, AustraliaSchool of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, AustraliaSchool of Medical Sciences, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, AustraliaCharles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia; Sydney Medical School, University of Sydney, Sydney, NSW 2006, AustraliaInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan; AMED-CREST, AMED, 1-7-1 Otemachi, Chiyoda-Ku, Tokyo 100-0004, JapanDepartment of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan; CREST, Japan Science and Technology Agency, Bunkyo-ku, Tokyo 113-0033, Japan; Corresponding authorSchool of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia; Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia; Corresponding authorSummary: 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. Keywords: adipocyte, insulin, glucose, metabolomics, metabolic tracer, metabolic priminghttp://www.sciencedirect.com/science/article/pii/S2211124717317527 |