The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Hormonal control of substrate cycling in humans.
Open accessAbstract
Recent studies have established the existence of substrate cycles in humans, but factors regulating the rate of cycling have not been identified. We have therefore investigated the acute response of glucose/glucose-6P-glucose (glucose) and triglyceride/fatty acid (TG/FA) substrate cycling to the infusion of epinephrine (0.03 microgram/kg.min) and glucagon. The response to a high dose glucagon infusion (2 micrograms/kg.min) was tested, as well as the response to a low dose infusion (5 ng/kg.min), with and without the simultaneous infusion of somatostatin (0.1 microgram/kg.min) and insulin (0.1 mU/kg.min). Additionally, the response to chronic prednisone (50 mg/d) was evaluated, both alone and during glucagon (low dose) and epinephrine infusion. Finally, the response to hyperglycemia, with insulin and glucagon held constant by somatostatin infusion and constant replacement of glucagon and insulin at basal rates, was investigated. Glucose cycling was calculated as the difference between the rate of appearance (Ra) of glucose as determined using 2-d1- and 6,6-d2-glucose as tracers. TG/FA cycling was calculated by first determining the Ra glycerol with d5-glycerol and the Ra FFA with [1-13C]palmitate, then subtracting Ra FFA from three times Ra glycerol. The results indicate that glucagon stimulates glucose cycling, and this stimulatory effect is augmented when the insulin response to glucagon infusion is blocked. Glucagon had minimal effect on TG/FA cycling. In contrast, epinephrine stimulated TG/FA cycling, but affected glucose cycling minimally. Prednisone had no direct effect on either glucose or TG/FA cycling, but blunted the stimulatory effect of glucagon on glucose cycling. Hyperglycemia, per se, had no direct effect on glucose or TG/FA cycling. Calculations revealed that stimulation of TG/FA cycling theoretically amplified the sensitivity of control of fatty acid flux, but no such amplification was evident as a result of the stimulation of glucose cycling by glucagon.
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“In studies addressing the effects of chronic GC treatment, typically no changes were observed in whole-body lipolysis in the fasted state [32], and fasting insulin levels were increased [33, 34].”
From Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial (2011) · cites this paper as [34]
Citations
Cites
Effects of arterial versus venous sampling on analysis of glucose kinetics in man
McGuire, E. A., Helderman, J. H., Tobin, J. D., Andres, R., & Berman, M. D. (1976) · Journal of Applied Physiology · doi:10.1152/jappl.1976.41.4.565 · Cited by 704
Clutter, W. E., Bier, D. M., Shah, S. D., & Cryer, P. E. (1980) · Journal of Clinical Investigation · doi:10.1172/jci109840 · Cited by 576
Effect of Severe Burn Injury on Substrate Cycling by Glucose and Fatty Acids
Wolfe, R. R., Herndon, D. N., Jahoor, F., Miyoshi, H., & Wolfe, M. (1987) · New England Journal of Medicine · doi:10.1056/nejm198708133170702 · Cited by 467
Self-citationRizza, R. A., Mandarino, L. J., & Gerich, J. E. (1982) · Diabetes · doi:10.2337/diab.31.8.663 · Cited by 440
Wegman, E. J., & Wright, I. W. (1983) · Journal of the American Statistical Association · doi:10.1080/01621459.1983.10477977 · Cited by 339
Futile Cycles in the Metabolism of Glucose
Katz, J. J., & Rognstad, R. (1976) · Current topics in cellular regulation · doi:10.1016/b978-0-12-152810-2.50013-9 · Cited by 319
Synergistic Interactions of Physiologic Increments of Glucagon, Epinephrine, and Cortisol in the Dog
Eigler, N., Saccà, L., & Sherwin, R. S. (1979) · Journal of Clinical Investigation · doi:10.1172/jci109264 · Cited by 260
Substrate cycles in metabolic regulation and in heat generation.
Newsholme, E. A., & Crabtree, B. (1976) · PubMed · Cited by 236
Glycerol turnover and oxidation in man
Bortz, W. M., Paul, P., Haff, A. C., & Holmes, W. L. (1972) · Journal of Clinical Investigation · doi:10.1172/jci106950 · Cited by 225
Tracers in metabolic research: radioisotope and stable isotope/mass spectrometry methods.
Wolfe, R. R. (1984) · PubMed · Cited by 220
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Fischer, J., Koch, L., Emmerling, C., Vierkotten, J., Peters, T., Brüning, J. C., & Rüther, U. (2009) · Nature · doi:10.1038/nature07848 · Cited by 964
Contributions of gluconeogenesis to glucose production in the fasted state
Landau, B. R., Wahren, J., Chandramouli, V, Schumann, W. C., Ekberg, K., & Kalhan, S. C. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118803 · Cited by 487
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Metadata
- Authors
- Miyoshi, H., Shulman, G. I., Peters, E. J., Wolfe, M. H., Elahi, D., & Wolfe, R. R.
- Affiliations
- Shriners Hospitals for Children - Galveston (US)
- Harvard University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1988-05-01
- Volume
- 81
- Issue
- 5
- Pages
- 1545-1555
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC442588
- OpenAlex
- W2007418665
- Cited by
- 139
- References
- 35
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 5 · 2012: 5
- FWCI
- 13.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK040936, DK34817)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- substrate cycling, glucagon, epinephrine, insulin, somatostatin, prednisone, hyperglycemia, fatty acid flux, hormonal regulation of metabolism
- MeSH terms
- Adult, Blood Glucose, Epinephrine, Fatty Acids, Glucagon, Glucose, Humans, Hyperglycemia, Insulin, Prednisone, Triglycerides
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