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Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men

Stephens, Francis B.; Chee, Carolyn; Wall, Benjamin T.; Murton, Andrew J.; Shannon, Chris E.; van Loon, Luc J.C.; Tsintzas, Kostas

Authors

Carolyn Chee

Benjamin T. Wall

Andrew J. Murton

Chris E. Shannon

Luc J.C. van Loon



Abstract

The ability to maintain skeletal muscle mass appears to be impaired in insulin-resistant conditions, such as type 2 diabetes, that are characterized by muscle lipid accumulation. The current study investigated the effect of acutely increasing lipid availability on muscle protein synthesis. Seven healthy young male volunteers underwent a 7-h intravenous infusion of l-[ring-2H5]phenylalanine on two randomized occasions combined with 0.9% saline or 10% Intralipid at 100 mL/h. After a 4-h “basal” period, a 21-g bolus of amino acids was administered and a 3-h hyperinsulinemic-euglycemic clamp was commenced (“fed” period). Muscle biopsy specimens were obtained from the vastus lateralis at 1.5, 4, and 7 h. Lipid infusion reduced fed whole-body glucose disposal by 20%. Furthermore, whereas the mixed muscle fractional synthetic rate increased from the basal to the fed period during saline infusion by 2.2-fold, no change occurred during lipid infusion, despite similar circulating insulin and leucine concentrations. This “anabolic resistance” to insulin and amino acids with lipid infusion was associated with a complete suppression of muscle 4E-BP1 phosphorylation. We propose that increased muscle lipid availability may contribute to anabolic resistance in insulin-resistant conditions by impairing translation initiation.

Journal Article Type Article
Publication Date May 1, 2015
Journal Diabetes
Print ISSN 0012-1797
Electronic ISSN 1939-327X
Publisher American Diabetes Association
Peer Reviewed Peer Reviewed
Volume 64
Issue 5
APA6 Citation Stephens, F. B., Chee, C., Wall, B. T., Murton, A. J., Shannon, C. E., van Loon, L. J., & Tsintzas, K. (2015). Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men. Diabetes, 64(5), https://doi.org/10.2337/db14-0961
DOI https://doi.org/10.2337/db14-0961
Publisher URL http://diabetes.diabetesjournals.org/content/64/5/1615
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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