Phosphorylation of AMPKα at Ser485/491 Is Dependent on Muscle Contraction and Not Muscle-Specific IGF-I Overexpression
Glucose is an important fuel for highly active skeletal muscles. Increased adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratios during repetitive contractions trigger AMP-activated protein kinase (AMPK), indicated by phosphorylation of AMPKα<sup>Thr172</sup>, which promotes...
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/15/11950 |
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| author | Chih-Hsuan Chou Elisabeth R. Barton |
| author_facet | Chih-Hsuan Chou Elisabeth R. Barton |
| author_sort | Chih-Hsuan Chou |
| collection | DOAJ |
| description | Glucose is an important fuel for highly active skeletal muscles. Increased adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratios during repetitive contractions trigger AMP-activated protein kinase (AMPK), indicated by phosphorylation of AMPKα<sup>Thr172</sup>, which promotes glucose uptake to support heightened energy needs, but it also suppresses anabolic processes. Inhibition of AMPK can occur by protein kinase B (AKT)-mediated phosphorylation of AMPKα<sup>Ser485/491</sup>, releasing its brake on growth. The influence of insulin-like growth factor I (IGF-I) on glucose uptake and its interplay with AMPK activation is not well understood. Thus, the goal of this study was to determine if increased muscle IGF-I altered AMPKα phosphorylation and activity during muscle contraction. Adult male mice harboring the rat <i>Igf1a</i> cDNA regulated by the fast myosin light chain promoter (<i>mIgf1<sup>+/+</sup></i>) and wildtype littermates (WT) were used in the study. <i>mIgf1<sup>+/+</sup></i> mice had enhanced glucose tolerance and insulin-stimulated glucose uptake, but similar exercise capacity. Fatiguing stimulations of extensor digitorum longus (EDL) muscles resulted in upregulated AMPKα phosphorylation at both Thr172 and Ser485/491 in WT and <i>mIgf1<sup>+/+</sup></i> muscles. No differences in the phosphorylation response of the downstream AMPK target TBC1D1 were observed, but phosphorylation of raptor was significantly higher only in WT muscles. Further, total raptor content was elevated in <i>mIgf1<sup>+/+</sup></i> muscles. The results show that high muscle IGF-I can enhance glucose uptake under resting conditions; however, in contracting muscle, it is not sufficient to inhibit AMPK activity. |
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| language | English |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1e586957f2ce4a2aa4b9b0f93702154b2023-11-18T22:58:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151195010.3390/ijms241511950Phosphorylation of AMPKα at Ser485/491 Is Dependent on Muscle Contraction and Not Muscle-Specific IGF-I OverexpressionChih-Hsuan Chou0Elisabeth R. Barton1Applied Physiology & Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, FL 32611, USAApplied Physiology & Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, FL 32611, USAGlucose is an important fuel for highly active skeletal muscles. Increased adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratios during repetitive contractions trigger AMP-activated protein kinase (AMPK), indicated by phosphorylation of AMPKα<sup>Thr172</sup>, which promotes glucose uptake to support heightened energy needs, but it also suppresses anabolic processes. Inhibition of AMPK can occur by protein kinase B (AKT)-mediated phosphorylation of AMPKα<sup>Ser485/491</sup>, releasing its brake on growth. The influence of insulin-like growth factor I (IGF-I) on glucose uptake and its interplay with AMPK activation is not well understood. Thus, the goal of this study was to determine if increased muscle IGF-I altered AMPKα phosphorylation and activity during muscle contraction. Adult male mice harboring the rat <i>Igf1a</i> cDNA regulated by the fast myosin light chain promoter (<i>mIgf1<sup>+/+</sup></i>) and wildtype littermates (WT) were used in the study. <i>mIgf1<sup>+/+</sup></i> mice had enhanced glucose tolerance and insulin-stimulated glucose uptake, but similar exercise capacity. Fatiguing stimulations of extensor digitorum longus (EDL) muscles resulted in upregulated AMPKα phosphorylation at both Thr172 and Ser485/491 in WT and <i>mIgf1<sup>+/+</sup></i> muscles. No differences in the phosphorylation response of the downstream AMPK target TBC1D1 were observed, but phosphorylation of raptor was significantly higher only in WT muscles. Further, total raptor content was elevated in <i>mIgf1<sup>+/+</sup></i> muscles. The results show that high muscle IGF-I can enhance glucose uptake under resting conditions; however, in contracting muscle, it is not sufficient to inhibit AMPK activity.https://www.mdpi.com/1422-0067/24/15/11950AMPKskeletal muscleIGF-Imuscle contraction |
| spellingShingle | Chih-Hsuan Chou Elisabeth R. Barton Phosphorylation of AMPKα at Ser485/491 Is Dependent on Muscle Contraction and Not Muscle-Specific IGF-I Overexpression International Journal of Molecular Sciences AMPK skeletal muscle IGF-I muscle contraction |
| title | Phosphorylation of AMPKα at Ser485/491 Is Dependent on Muscle Contraction and Not Muscle-Specific IGF-I Overexpression |
| title_full | Phosphorylation of AMPKα at Ser485/491 Is Dependent on Muscle Contraction and Not Muscle-Specific IGF-I Overexpression |
| title_fullStr | Phosphorylation of AMPKα at Ser485/491 Is Dependent on Muscle Contraction and Not Muscle-Specific IGF-I Overexpression |
| title_full_unstemmed | Phosphorylation of AMPKα at Ser485/491 Is Dependent on Muscle Contraction and Not Muscle-Specific IGF-I Overexpression |
| title_short | Phosphorylation of AMPKα at Ser485/491 Is Dependent on Muscle Contraction and Not Muscle-Specific IGF-I Overexpression |
| title_sort | phosphorylation of ampkα at ser485 491 is dependent on muscle contraction and not muscle specific igf i overexpression |
| topic | AMPK skeletal muscle IGF-I muscle contraction |
| url | https://www.mdpi.com/1422-0067/24/15/11950 |
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