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Perfusion Time [min)

Figure 2, Subs I rate oxidation rates before and after contractile stimulation. G. W. Goodwill ct al. J Biol Chem 273, 29530-9(1998).

in workload of the heart is accompanied by increases in [AMP] and intracellular free [glucose]. While AMP activates phosphoiylase and promotes glycogen breakdown, free glucose inhibits phosphoiylase and promotes glycogen synthesis (via an increase in glucose 6-phosphiite and inhibition of glycogen synthase kinase). Thus, the metabolite measurements depicted in Figure 3 serve as illustrations for metabolic signals regulating fluxes through metabolic pathways and, hence, determining metabolic flexibility.

However, adaptations to sustained or chronic changes in the environment induce changes of the metabolic machinery at a transcriptional and/or translational level of the enzymes of metabolic pathways. We proposed earlier that metabolic remodeling precedes, triggers, and maintains structural and functional remodeling of the heart." Here the nuclear receptor PPARa and its coactivator PGC-1 need to be mentioned again, because they have been identified as master-switches for the metabolic remodeling of the heart.,6 ,s For example, pressure overload1'-1 and unloading of the heart,2" hypoxia,21 and, unexpectedly, also insulin-deficient diabetes22 all result in the downregulation of genes controlling fatty acid oxidation and in reactivation of the fetal gene program {Fig. 4). These recent observations are in line with earlier work showing increased glucose metabolic activity in the pressure overloaded heart,23 even before the onset of hypertrophy.24 They are also in line with work showing impaired fatty acid oxidation by failing heart muscle in vitro,25 and in vivo.26,27 We have proposed that metabolic flexibility is lost in diseased heart.28 Richard Shannon's group has recently presented evidence for the development of myocardial insulin resistance in conscious dogs with advanced dilated cardiomyopathy induced by rapid ventricular pacing.29


Phosphorylase Kinase b©

Phosphorylase Kinase b©


Phosphorylase Kinase a©

AMP Phosphorylase b r

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Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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