Insulin and Sarcopenia in the Elderly

Summary

Muscle loss with aging is a significant contributor to disability in older people. Our general hypothesis is that loss of muscle with aging, known as sarcopenia, may be due to inability of muscle to grow in response to insulin. Our goal is to determine the mechanisms underlying this age-related insulin resistance of muscle proteins, which will allow us to define in the future specific interventions to target this defect and provide the scientific basis for the prevention and treatment of sarcopenia.

Timeline

Start

2005-09

Primary completion

2012-08

Completion

2012-08

Publications

• Results Rasmussen BB, Fujita S, Wolfe RR, Mittendorfer B, Roy M, Rowe VL, Volpi E. Insulin resistance of muscle protein metabolism in aging. FASEB J. 2006 Apr;20(6):768-9. doi: 10.1096/fj.05-4607fje. Epub 2006 Feb 7.
• Results Bell JA, Volpi E, Fujita S, Cadenas JG, Sheffield-Moore M, Rasmussen BB. Skeletal muscle protein anabolic response to increased energy and insulin is preserved in poorly controlled type 2 diabetes. J Nutr. 2006 May;136(5):1249-55. doi: 10.1093/jn/136.5.1249.
• Results Bell JA, Volpi E, Fujita S, Cadenas JG, Rasmussen BB. Dysregulation of muscle fatty acid metabolism in type 2 diabetes is independent of malonyl-CoA. Diabetologia. 2006 Sep;49(9):2144-52. doi: 10.1007/s00125-006-0362-9. Epub 2006 Jul 26.
• Results Timmerman KL, Volpi E. Amino acid metabolism and regulatory effects in aging. Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):45-9. doi: 10.1097/MCO.0b013e3282f2a592.
• Results Fujita S, Volpi E. Amino acids and muscle loss with aging. J Nutr. 2006 Jan;136(1 Suppl):277S-80S. doi: 10.1093/jn/136.1.277S.
• Results Dreyer HC, Volpi E. Role of protein and amino acids in the pathophysiology and treatment of sarcopenia. J Am Coll Nutr. 2005 Apr;24(2):140S-145S. doi: 10.1080/07315724.2005.10719455.
• Results Drummond MJ, Bell JA, Fujita S, Dreyer HC, Glynn EL, Volpi E, Rasmussen BB. Amino acids are necessary for the insulin-induced activation of mTOR/S6K1 signaling and protein synthesis in healthy and insulin resistant human skeletal muscle. Clin Nutr. 2008 Jun;27(3):447-56. doi: 10.1016/j.clnu.2008.01.012. Epub 2008 Mar 14.
• Results Drummond MJ, Dreyer HC, Pennings B, Fry CS, Dhanani S, Dillon EL, Sheffield-Moore M, Volpi E, Rasmussen BB. Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging. J Appl Physiol (1985). 2008 May;104(5):1452-61. doi: 10.1152/japplphysiol.00021.2008. Epub 2008 Mar 6.
• Results Fujita S, Rasmussen BB, Cadenas JG, Drummond MJ, Glynn EL, Sattler FR, Volpi E. Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling. Diabetes. 2007 Jun;56(6):1615-22. doi: 10.2337/db06-1566. Epub 2007 Mar 9.
• Results Fujita S, Rasmussen BB, Bell JA, Cadenas JG, Volpi E. Basal muscle intracellular amino acid kinetics in women and men. Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E77-83. doi: 10.1152/ajpendo.00173.2006. Epub 2006 Aug 8.
• Results Fujita S, Rasmussen BB, Cadenas JG, Grady JJ, Volpi E. Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability. Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E745-54. doi: 10.1152/ajpendo.00271.2005. Epub 2006 May 16.
• Results Bell JA, Fujita S, Volpi E, Cadenas JG, Rasmussen BB. Short-term insulin and nutritional energy provision do not stimulate muscle protein synthesis if blood amino acid availability decreases. Am J Physiol Endocrinol Metab. 2005 Dec;289(6):E999-1006. doi: 10.1152/ajpendo.00170.2005. Epub 2005 Jul 19.
• Results Volpi E, Chinkes DL, Rasmussen BB. Sequential muscle biopsies during a 6-h tracer infusion do not affect human mixed muscle protein synthesis and muscle phenylalanine kinetics. Am J Physiol Endocrinol Metab. 2008 Oct;295(4):E959-63. doi: 10.1152/ajpendo.00671.2007. Epub 2008 Aug 19.
• Results Drummond MJ, Miyazaki M, Dreyer HC, Pennings B, Dhanani S, Volpi E, Esser KA, Rasmussen BB. Expression of growth-related genes in young and older human skeletal muscle following an acute stimulation of protein synthesis. J Appl Physiol (1985). 2009 Apr;106(4):1403-11. doi: 10.1152/japplphysiol.90842.2008. Epub 2008 Sep 11.
• Results Fujita S, Glynn EL, Timmerman KL, Rasmussen BB, Volpi E. Supraphysiological hyperinsulinaemia is necessary to stimulate skeletal muscle protein anabolism in older adults: evidence of a true age-related insulin resistance of muscle protein metabolism. Diabetologia. 2009 Sep;52(9):1889-98. doi: 10.1007/s00125-009-1430-8. Epub 2009 Jul 9.
• Results Timmerman KL, Lee JL, Dreyer HC, Dhanani S, Glynn EL, Fry CS, Drummond MJ, Sheffield-Moore M, Rasmussen BB, Volpi E. Insulin stimulates human skeletal muscle protein synthesis via an indirect mechanism involving endothelial-dependent vasodilation and mammalian target of rapamycin complex 1 signaling. J Clin Endocrinol Metab. 2010 Aug;95(8):3848-57. doi: 10.1210/jc.2009-2696. Epub 2010 May 19.
• Results Timmerman KL, Lee JL, Fujita S, Dhanani S, Dreyer HC, Fry CS, Drummond MJ, Sheffield-Moore M, Rasmussen BB, Volpi E. Pharmacological vasodilation improves insulin-stimulated muscle protein anabolism but not glucose utilization in older adults. Diabetes. 2010 Nov;59(11):2764-71. doi: 10.2337/db10-0415. Epub 2010 Aug 19.
• Results Drummond MJ, McCarthy JJ, Sinha M, Spratt HM, Volpi E, Esser KA, Rasmussen BB. Aging and microRNA expression in human skeletal muscle: a microarray and bioinformatics analysis. Physiol Genomics. 2011 May 1;43(10):595-603. doi: 10.1152/physiolgenomics.00148.2010. Epub 2010 Sep 28.
• Results Timmerman KL, Dhanani S, Glynn EL, Fry CS, Drummond MJ, Jennings K, Rasmussen BB, Volpi E. A moderate acute increase in physical activity enhances nutritive flow and the muscle protein anabolic response to mixed nutrient intake in older adults. Am J Clin Nutr. 2012 Jun;95(6):1403-12. doi: 10.3945/ajcn.111.020800. Epub 2012 May 9.
• Results Drummond MJ, Dickinson JM, Fry CS, Walker DK, Gundermann DM, Reidy PT, Timmerman KL, Markofski MM, Paddon-Jones D, Rasmussen BB, Volpi E. Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults. Am J Physiol Endocrinol Metab. 2012 May 15;302(9):E1113-22. doi: 10.1152/ajpendo.00603.2011. Epub 2012 Feb 14.
• Results Drummond MJ, Timmerman KL, Markofski MM, Walker DK, Dickinson JM, Jamaluddin M, Brasier AR, Rasmussen BB, Volpi E. Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults. Am J Physiol Regul Integr Comp Physiol. 2013 Aug 1;305(3):R216-23. doi: 10.1152/ajpregu.00072.2013. Epub 2013 Jun 12.

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