Insulin resistance and sarcopenia: mechanistic links between common co-morbidities
- 1Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London, UK
- 2Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
- 3Division of Medical Sciences and Graduate Entry Medicine, University of Nottingham, Medical School, Royal Derby Hospital, Derby, UK
- Correspondence should be addressed to M E Cleasby; Email: mcleasby{at}rvc.ac.uk
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Figure 1
Clinical characterisation of sarcopenic obesity (SO). Sarcopenia, obesity and insulin resistance (IR) increase in prevalence with advancing age. When individuals display several of the clinical signs listed, they may be defined as showing SO. Dotted arrows indicate likely causative relationships and suggest that IR may be central to the syndrome.
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Figure 2
Insulin resistance and ‘Anabolic resistance’ in skeletal muscle and the role of intramyocellular lipid (IMCL) deposition. (A) Normal muscle of young adult. Protein synthesis predominates over proteolysis under stimulation by supply of essential amino acids and insulin. Optimal insulin sensitivity favours glucose disposal and oxidation of lipids. (B) Muscle of aged adult with sarcopenic obesity. Obesity-associated increases in intramyocellular lipid deposition, among other factors, causes impaired insulin signalling, protein synthesis and glucose metabolism. There is also a reduced anabolic response to exercise, amino acids and insulin. However, the extent of this resistance to insulin on protein, lipid and glucose metabolism varies between individuals. Straight arrows: metabolite flux. Broken straight arrows: reduced metabolite flux. Filled curved arrows: stimulatory effect. Open curved arrows: inhibitory effect.
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Figure 3
Roles of selected candidate molecular mediators in skeletal muscle glucose and protein metabolism. Published effects of insulin, insulin-like growth factor 1 (IGF1), amino acids, myostatin, urocortins and vitamin D on signalling pathways and effector machinery (glucose transporters, mitochondrial function, translation and activation of E3 ubiquitin ligases) relating to glucose and protein metabolism, as discussed in the text. Unmarked arrow: movement of molecules. Arrow with ‘+’: direct stimulatory effect on expression or activity. Arrow with ‘−’: direct inhibitory effect on expression or activity. Broken arrow: indirect effect. P indicates phosphorylation. ACT2BR, activin 2B receptor; AMPK, AMP-activated protein kinase; AS160, Akt substrate of 160 kDa; CRFR2, corticotrophin-releasing factor receptor 2; FOXO, forkhead transcription factor; GLUT4, glucose transporter 4; IGF1R, IGF1 receptor; NFκB, nuclear factor κB; PGC1α, peroxisome proliferator-activated receptor coactivator 1α; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; PI3K, phosphoinositol 3-kinase; SIRT1, sirtuin 1; VDR, vitamin D receptor.
- © 2016 The authors
