Muscle adaptation to short-term fasting in healthy lean humans
Abstract
Context: It has been demonstrated repeatedly that short-term fasting induces insulin resistance, although the exact mechanism in humans is unknown to date. Intramyocellular sphingolipids (i.e. ceramide) have been suggested to induce insulin resistance by interfering with the insulin signaling cascade in obesity. Objective: Our objective was to study peripheral insulin sensitivity together with muscle ceramide concentrations and protein kinase B/AKT phosphorylation after short-term fasting. Main Outcome Measures and Design: After 14- and 62-h fasting, glucose fluxes were measured before and after a hyperinsulinemic euglycemic clamp. Muscle biopsies were performed in the basal state and during the clamp to assess muscle ceramide and protein kinase B/AKT. Results: Insulin-mediated peripheral glucose uptake was significantly lower after 62-h fasting compared with 14-h fasting. Intramuscular ceramide concentrations tended to increase during fasting. During the clamp the phosphorylation of protein kinase B/AKT at serine473 in proportion to the total amount of protein kinase B/AKT was significantly lower. Muscle ceramide did not correlate with plasma free fatty acids. Conclusions: Fasting for 62 h decreases insulin-mediated peripheral glucose uptake with lower phosphorylation of AKT at serine473. AKT may play a regulatory role in fasting-induced insulin resistance. Whether the decrease in AKT can be attributed to the trend to higher muscle ceramide remains unanswered.
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Not all studies show the effect of prolonged fasting on metabolic flexibility.
“However, not all studies show this effect (41).”
From Prolonged fasting identifies skeletal muscle mitochondrial dysfunction as consequence rather than cause of human insulin resistance (2010) · cites this paper as [41]
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“Elevated FFA can impair intramuscular glucose metabolism through direct competition between substrates (Hue & Taegtmeyer, 2009; Randle et al., 1964; Sugden et al., 2001) and/or lipid-mediated inhibition of insulin signalling (Soeters et al., 2008; Vendelbo et al., 2012; Yu et al., 2002).”
- Authors
- Soeters, M. R., Sauerwein, H. P., Dubbelhuis, P. F., Groener, J. E., Ackermans, M. T., Fliers, E., Aerts, J. M., & Serlie, M. J.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Departments of Clinical Chemistry (M.T.A.), Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands
- Corresponding author
- Soeters, Maarten R.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2008-07-01
- Volume
- 93
- Issue
- 7
- Pages
- 2900-2903
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2047173938
- Cited by
- 40
- References
- 23
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 3 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 4 · 2012: 4
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- short-term fasting, insulin resistance, skeletal muscle, ceramide, sphingolipids, Akt phosphorylation, Akt, insulin signaling, glucose uptake, hyperinsulinemic-euglycemic clamp, plasma free fatty acids
- MeSH terms
- Adaptation, Physiological, Adult, Ceramides, Fasting, Fatty Acids, Nonesterified, Glucose, Humans, Insulin Resistance, Male, Phosphorylation, Thinness, Muscle, Skeletal, Proto-Oncogene Proteins c-akt
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