Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men
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 hea...
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| Format: | Article |
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American Diabetes Association
2015
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| Online Access: | https://eprints.nottingham.ac.uk/44958/ |
| _version_ | 1848797038137835520 |
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| author | Stephens, Francis B. Chee, Carolyn Wall, Benjamin T. Murton, Andrew J. Shannon, Chris E. van Loon, Luc J.C. Tsintzas, Kostas |
| author_facet | Stephens, Francis B. Chee, Carolyn Wall, Benjamin T. Murton, Andrew J. Shannon, Chris E. van Loon, Luc J.C. Tsintzas, Kostas |
| author_sort | Stephens, Francis B. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:57:31Z |
| format | Article |
| id | nottingham-44958 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:57:31Z |
| publishDate | 2015 |
| publisher | American Diabetes Association |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-449582020-05-04T17:05:31Z https://eprints.nottingham.ac.uk/44958/ 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 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. American Diabetes Association 2015-05-01 Article PeerReviewed Stephens, Francis B., Chee, Carolyn, Wall, Benjamin T., Murton, Andrew J., Shannon, Chris E., van Loon, Luc J.C. and Tsintzas, Kostas (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). pp. 1615-1620. ISSN 1939-327X http://diabetes.diabetesjournals.org/content/64/5/1615 doi:10.2337/db14-0961 doi:10.2337/db14-0961 |
| spellingShingle | Stephens, Francis B. Chee, Carolyn Wall, Benjamin T. Murton, Andrew J. Shannon, Chris E. van Loon, Luc J.C. Tsintzas, Kostas Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men |
| title | Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men |
| title_full | Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men |
| title_fullStr | Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men |
| title_full_unstemmed | Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men |
| title_short | Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men |
| title_sort | lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men |
| url | https://eprints.nottingham.ac.uk/44958/ https://eprints.nottingham.ac.uk/44958/ https://eprints.nottingham.ac.uk/44958/ |