Deoxyglucose

Publication Title: 
Biogerontology

2-Deoxy-D-glucose (2-DG) and dehydroepiandrosterone (DHEA) have been hypothesized to extend lifespan via mimicking calorie restriction (CR). Activation of sirtuins has been proposed to contribute to life extension of CR by increasing intercellular levels of NAD(+) in several organisms. However, it is unclear whether 2-DG and DHEA may affect intracellular NAD(+) levels and human sirtuin 1 (SIRT1) activities. Here, using human fibroblast Hs68 cells we showed that 2-DG increased intracellular NAD(+) levels in both time- and concentration-dependent manners.

Author(s): 
Yang, Nae-Cherng
Song, Tuzz-Ying
Chen, Mei-Yau
Hu, Miao-Lin
Publication Title: 
Annals of the New York Academy of Sciences

Dietary caloric restriction (CR) is the only intervention conclusively and reproducibly shown to slow aging and maintain health and vitality in mammals. Although this paradigm has been known for over 60 years, its precise biological mechanisms and applicability to humans remain unknown. We began addressing the latter question in 1987 with the first controlled study of CR in primates (rhesus and squirrel monkeys, which are evolutionarily much closer to humans than the rodents most frequently employed in CR studies).

Author(s): 
Roth, G. S.
Ingram, D. K.
Lane, M. A.
Publication Title: 
Scientific American
Author(s): 
Lane, Mark A.
Ingram, Donald K.
Roth, George S.
Publication Title: 
Annals of the New York Academy of Sciences

By applying calorie restriction (CR) at 30-50% below ad libitum levels, studies in numerous species have reported increased life span, reduced incidence and delayed onset of age-related diseases, improved stress resistance, and decelerated functional decline. Whether this nutritional intervention is relevant to human aging remains to be determined; however, evidence emerging from CR studies in nonhuman primates suggests that response to CR in primates parallels that observed in rodents. To evaluate CR effects in humans, clinical trials have been initiated.

Author(s): 
Ingram, Donald K.
Anson, R. Michael
de Cabo, Rafael
Mamczarz, Jacek
Zhu, Min
Mattison, Julie
Lane, Mark A.
Roth, George S.
Publication Title: 
Annals of the New York Academy of Sciences

Calorie restriction (CR) mimetics are agents or strategies that can mimic the beneficial health-promoting and anti-aging effects of CR, the only intervention conclusively shown to slow aging and maintain health and vitality across the phylogenetic spectrum. Our lead compound, developed at the National Institute on Aging, was 2-deoxyglucose, an analogue of the native sugar, that acted as a glycolytic inhibitor, having limited metabolism and actually reducing overall energy flow--analogous to CR.

Author(s): 
Roth, George S.
Lane, Mark A.
Ingram, Donald K.
Publication Title: 
Neuroscience Letters

The rates of local cerebral glucose utilization have been measured in normal conscious and hypnotized rabbits by the [14C]deoxyglucose method. In control rabbits the rates vary widely throughout the brain, with the values in gray matter broadly distributed around an average which is about 3 times greater than that of white matter. The higher values area in structures of auditory system (superior olive, inferior colliculus, auditory cortex).

Author(s): 
Passero, S.
Carli, G.
Battistini, N.
Publication Title: 
Psychiatry Research

In an attempt to elucidate the physiological basis of hypnosis, we investigated the changes of whole-brain and regional cerebral glucose metabolism, from a state of resting wakefulness to a hypnotized state with whole-body catalepsy, using positron emission tomography and the 2[18F]fluorodeoxyglucose method in 15 highly hypnotizable adults. Neither the random order of study conditions nor any of the other experimental factors had a measurable effect, and there was no statistically significant global activation or metabolic depression.

Author(s): 
Grond, M.
Pawlik, G.
Walter, H.
Lesch, O. M.
Heiss, W. D.
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

The intraerythrocytic stage of the human malaria parasite Plasmodium falciparum relies on glycolysis for ATP generation, and because it has no energy stores, a constant supply of glucose is necessary for the parasite to grow and multiply. The 2-substituted glucose analogs 2-deoxy-D-glucose (2-DG) and 2-fluoro-2-deoxy-D-glucose (2-FG) have been previously shown to inhibit the in vitro growth of P. falciparum and have been suggested to do so by inhibiting glycosylation in the parasite.

Author(s): 
van Schalkwyk, Donelly A.
Priebe, Waldemar
Saliba, Kevin J.
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Glucose serves as the major energy substrate and the main precursor for the synthesis of glycosaminoglycans in chondrocytes. Facilitated glucose transport represents the first rate-limiting step in glucose metabolism. This study examines molecular regulation of facilitated glucose transport in normal human articular chondrocytes by proinflammatory cytokines. IL-1beta and TNF-alpha, and to a lesser degree IL-6, accelerate facilitated glucose transport as measured by [(3)H]2-deoxyglucose uptake.

Author(s): 
Shikhman, A. R.
Brinson, D. C.
Valbracht, J.
Lotz, M. K.
Publication Title: 
The Journal of Biological Chemistry

Cell culture work suggests that signaling to polymerize cortical filamentous actin (F-actin) represents a required pathway for the optimal redistribution of the insulin-responsive glucose transporter, GLUT4, to the plasma membrane. Recent in vitro study further suggests that the actin-regulatory neural Wiskott-Aldrich syndrome protein (N-WASP) mediates the effect of insulin on the actin filament network. Here we tested whether similar cytoskeletal mechanics are essential for insulin-regulated glucose transport in isolated rat epitrochlearis skeletal muscle.

Author(s): 
Brozinick, Joseph T.
Hawkins, Eric D.
Strawbridge, Andrew B.
Elmendorf, Jeffrey S.

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