Altitude training as a powerful corrective intervention in correctin insulin resistance
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- 운동영양학회지
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- 제16권2호
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- pp.65-71
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- 2012
Oxygen is the final acceptor of electron transport from fat and carbohydrate oxidation, which is the rate-limiting factor for cellular ATP production. Under altitude hypoxia condition, energy reliance on anaerobic glycolysis increases to compensate for the shortfall caused by reduced fatty acid oxidation [1]. Therefore, training at altitude is expected to strongly influence the human metabolic system, and has the potential to be designed as a non-pharmacological or recreational intervention regimen for correcting diabetes or related metabolic problems. However, most people cannot accommodate high altitude exposure above 4500 M due to acute mountain sickness (AMS) and insulin resistance corresponding to a increased levels of the stress hormones cortisol and catecholamine [2]. Thus, less stringent conditions were evaluated to determine whether glucose tolerance and insulin sensitivity could be improved by moderate altitude exposure (below 4000 M). In 2003, we and another group in Austria reported that short-term moderate altitude exposure plus endurance-related physical activity significantly improves glucose tolerance (not fasting glucose) in humans [3,4], which is associated with the improvement in the whole-body insulin sensitivity [5]. With daily hiking at an altitude of approximately 4000 M, glucose tolerance can still be improved but fasting glucose was slightly elevated. Individuals vary widely in their response to altitude challenge. In particular, the improvement in glucose tolerance and insulin sensitivity by prolonged altitude hiking activity is not apparent in those individuals with low baseline DHEA-S concentration [6]. In addition, hematopoietic adaptation against altitude hypoxia can also be impaired in individuals with low DHEA-S. In short-lived mammals like rodents, the DHEA-S level is barely detectable since their adrenal cortex does not appear to produce this steroid [7]. In this model, exercise training recovery under prolonged hypoxia exposure (14-15% oxygen, 8 h per day for 6 weeks) can still improve insulin sensitivity, secondary to an effective suppression of adiposity [8]. Genetically obese rats exhibit hyperinsulinemia (sign of insulin resistance) with up-regulated baseline levels of AMP-activated protein kinase and AS160 phosphorylation in skeletal muscle compared to lean rats. After prolonged hypoxia training, this abnormality can be reversed concomitant with an approximately 50% increase in GLUT4 protein expression. Additionally, prolonged moderate hypoxia training results in decreased diffusion distance of muscle fiber (reduced cross-sectional area) without affecting muscle weight. In humans, moderate hypoxia increases postprandial blood distribution towards skeletal muscle during a training recovery. This physiological response plays a role in the redistribution of fuel storage among important energy storage sites and may explain its potent effect on changing body composition. Conclusion: Prolonged moderate altitude hypoxia (rangingfrom 1700 to 2400 M), but not acute high attitude hypoxia (above 4000 M), can effectively improve insulin sensitivity and glucose tolerance for humans and antagonizes the obese phenotype in animals with a genetic defect. In humans, the magnitude of the improvementvaries widely and correlates with baseline plasma DHEA-S levels. Compared to training at sea-level, training at altitude effectively decreases fat mass in parallel with increased muscle mass. This change may be associated with increased perfusion of insulin and fuel towards skeletal muscle that favors muscle competing postprandial fuel in circulation against adipose tissues.
Many of the measures and policies advocated by supply-siders, such as lower taxation, less government intervention, more freedom from restrictive legislation and regulation, and the need for increased productivity can be found in writing the classical economist. Nor is supply-side economics a complete divorcement from Keynesian analysis. In both camps the objectives are the same-high level employment, stable prices and healthy economic growth, the means or suggestions for attaining the objectives, however, differ. Consequently, recommended economic policies and measures are different. keynesians rely primarily on the manipulation of effective demand to increase output and employment and to combat inflation. They assume ample resources to be available in order that supply will respond to demand. The supply-siders emphasize the need to increase savings, investment, productivity and output as a means of increasing income. Supply-siders assume that the increase in income will lead to an increase in effective demand. Keynesians suggest that savings, particularly those not invested, dampen economic activity. Supply-siders hold that savings, or at least an increase in after-tax income, stimulates work effort and provides funds for investment. Perhaps keynesians are guilty of assuming that most savings are not going to be invested, whereas supply-siders may erroneously assume that almost all savings will flow into investment and/ or stimulate work effort. In reality, a middle ground is possible. The supply-siders stress the need to increase supply, but Keynes did not preclude the possibility of increasing economic activity by working through the supply side. According to Keynes' aggregate demand-aggregate supply framework, a decrease in supply will increase output and employment. It must be remembered, however, that Keynes' aggregate supply is really a price. Lowering the price or cost of supply would there by result in higher profit and/ or higher output. This coincides with the viewpoint of supply-siders who want to lower the cost of production via various means for the purpose of increasing supply. Then, too, some of the means, such as tax cuts, tax credits and accelerated depreciation, recommended by suply-siders to increase productivity and output would be favored by Keynesians also as a means of increasing investment, curbing costs, and increasing effective demand. In fact, these very measures were used in the early 1960s in the United State during the years when nagging unemployment was plaguing the economy. Keynesians disagree with the supply-siders' proposals to reduce transfer payments and slow down the process of income redistribution, except in full employment inflationary periods. Keynesians likewise disagree with tax measures that favored business as opposed to individuals and the notion of shifting the base of personal taxation away from income and toward spending. A frequent criticism levied at supply-side economics is that it lacks adequate models and thus far has not been quantified to any great extent. But, it should be remembered that Keynesian economics originally was lacking in models and based on a number of unproved assumptions, such as, the stability of the consumption function with its declining marginal propensity to consume. Just as the economic catastrophe of the great depression of the 1930s paved the way for the application of Keynesian or demand-side policies, perhaps the frustrating and restless conditions of the 1970s and 1980s is an open invitation for the application of supply-side policies. If so, the 1980s and 1990s may prove to be the testing era for the supply-side theories. By the end of 1990s we should have better supply-side models and know much more about the effectiveness of supply-side policies. By that time, also, supply-side thinking may be more crystallized and we will learn whether it is something temporary that will fade away, be widely accepted as the new economics replacing Keynesian demand analysis, or something to be continued but melded or fused with demand management.