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【drug-news】药物可以增加运动员的耐力
The study is published in the 31st July advanced online edition of Cell and is the work of researchers at the Salk Institute for Biological Studies, La Jolla, California, and other colleagues.
The discovery should help to develop treatments for muscle diseases and a range of metabolic disorders, including diabetes, and any athletes tempted to use the drugs, which are not commercially available, to boost performance in the coming Olympics can forget it since the lead researcher is already working with anti-doping officials to get a test for the drugs in place for this summer's games, according to a statement from the Salk Institute.
Led by Howard Hughes Medical Investigator Dr Ronald M Evans, a professor in the Gene Expression Laboratory at the Salk Institute, the investigators found that triggering two signalling pathways with oral drugs turned laboratory mice into long-distance runners and appeared to confer other benefits of exercise.
Using genetic engineering, Evans and his team had already found that switching on a gene pathway called PPAR delta turned laboratory mice into marathon runners. Also, when fed a high fat diet that made other mice obese, the treated mice did not gain weight, and their response to insulin also improved, and reduced their blood sugar levels.
Evans said they wanted to find out if a drug could produce the same effect on PPAR delta, since genetic engineering (called genetic doping when referring to athletic performance), although feasible, was not a practical solution for humans.
They focused on an experimental drug called GW1516 that seemed to fit the bill and fed it to laboratory mice for four weeks. The drug is not available commercially. But they were surprised by the results, as lead author and postdoctoral researcher, Dr Vihang A Narkar explained:
"We got the expected benefits in lowering fatty acids and blood glucose levels but no effect, absolutely none, on exercise performance."
So Narkar decided to try the next stage: would the drug show the desired effect if the mice were to have some exercise? So he had them run for up to 50 minutes every day on a treadmill.
This produced the desired effect; endurance in exercising mice treated with GW1516 went up by 77 per cent compared to exercising mice not on the drug. The drug also increased the proportion of "non-fatiguing" or "slow twitch"muscle fibres, said Narkar.
It would appear that GW1516 alone only boosted endurance and affected the muscle fibres when combined with some exercise. Narkar said they wondered if this was because of ATP, the chemical that delivers energy to muscles. When the body's demand for energy is high, ATP releases all its energy and becomes AMP, and when AMP goes up, it triggers AMPK, a metabolic regulator that increases production of ATP. They wondered if perhaps PPAR delta only got involved once the AMPK switched on.
AMPK normally resides in the cytoplasm that surrounds the nucleus of each cell, but closer inspection revealed that in this experiment, some exercise-activated AMPK molecules had got into the nucleus, interacted with the PPAR delta and increased its effect on endurance.
"It essentially puts a turbo charge on PPAR delta, which explains why exercise is so important," explained Evans.
So all that remained was to find a way to produce the same ATP-AMP effect without exercise. In a further experiment, the investigatos fed untrained mice a substance called AICAR, a synthetic vesion of AMP that triggers the AMPK switch directly.
After four weeks, with no training, the mice on synthetic AMP were able to run 44 per cent longer than untreated, untrained mice. Narkar said that was about the same improvement we can get with regular exercise.
The researchers concluded that:
" These results demonstrate that AMPK-PPAR delta pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise."
However, before the couch potatoes and aspiring Olympic contenders get tempted by the idea of taking "exercise in a pill", they may wish to reflect on the fact that Evans is already working officials at the World Anti-Doping Association on a blood and urine test that detects AICAR, GW1516 and its metabolites.
"AMPK and PPARdelta Agonists Are Exercise Mimetics."
Vihang A. Narkar, Michael Downes, Ruth T. Yu, Emi Embler, Yong-Xu Wang, Ester Banayo, Maria M. Mihaylova, Michael C. Nelson, Yuhua Zou, Henry Juguilon, Heonjoong Kang, Reuben J. Shaw, and Ronald M. Evans.
Cell Advance online edition 31 July 2008
DOI: 10.1016/j.cell.2008.06.051
http://www.mphtimes.com/bbs/viewthread.php?tid=2708&extra=page%3D1&frombbs=1
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作者:admin@医学,生命科学 2011-05-01 17:14
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