Award details

Equipment to measure leg blood flow and tissue amino acids in determining the molecular basis of nutrient sensitivity of human muscle protein turnover

Reference	BB/C511080/1
Principal Investigator / Supervisor	Professor Michael Rennie
Co-Investigators / Co-Supervisors	Professor Paul Greenhaff, Dr Kenneth Smith
Institution	University of Nottingham
Department	Sch of Biomedical Sciences
Funding type	Research
Value (£)	72,271
Status	Completed
Type	Research Grant
Start date	01/12/2004
End date	30/11/2005
Duration	12 months

Abstract

This application makes the case for resources to fund the purchase of a dedicated amino acid analyser and also a Doppler blood flow measurement instrument to facilitate human metabolic research, namely the elucidation of the molecular mechanisms underlying the dietary responses of skeletal muscle and bone, in particular their anabolic sensitivity and responsiveness to essential amino acids (EAA). The proposed programme of research, which will be funded by currently held grants, from BBSRC, Diabetes UK, NERC, WADA and the US NIH, as well as grants pending and those to be applied for the near future built upon recent results demonstrating the dose-response relationship between the availability of EAA in plasma and muscle protein synthesis. This relationship is an important one for control of the size of the skeletal muscle mass by diet and appears to be markedly deranged in ageing and type 2 diabetes. The work is also built upon our recent discoveries demonstrating for the first time that human bone collagen is acutely sensitive to feeding. In addition to the phenotypic read-outs of muscle protein synthesis and breakdown, which will be examined under a number of circumstances in which square-wave changes in amino acids availability is applied to determine the responses in muscle and bone, we were examining alterations of expression of mRNA for a number of transcription factors, proteolytic enzymes and also signalling molecules such as those in the mTOR pathway. These constituents, such as mTOR itself, p70 S6 kinase, eIF2B and eIF-4B P1 have recently been shown by us to exhibit markedly different responses in phosphorylation between elderly and young subjects. Thus we are in a position to begin to unravel many of the inter relating factors affecting control of muscle protein synthesis in muscle and bone in response to availability of amino acids and insulin, using analytical techniques ranging from the sub-cellular and molecular through techniques appropriate for the study of whole organs and the whole body ¿ truly integrative physiology in the terms of the Animal Sciences Initiative.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Research Equipment Initiative 2004 (RE4) [2004]
Funding Scheme	X – not Funded via a specific Funding Scheme

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