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NADH / NAD ATP/ADP pyruvate/lactate p<0.05

0.5 mM R-lipoate treatment for 24 hours

Figure 4 Effect of R-lipoate treatment on redox status and ATP/ADP ratio in Wurzburg T cells.

Dehydroascorbate w Dihydrolipoate

This may contribute to the hypoglycemic effect of Lipoate

Dehydroascorbate w Dihydrolipoate

Ascorbate k

This may contribute to the hypoglycemic effect of Lipoate

Lipoate

Figure 5 Proposed mechanism whereby a-lipoic acid stimulates glucose uptake.

1. Lipoic acid, when it became reduced, would be exported from the cells as dihydrolipoic acid; this in turn could regenerate vitamin C radicals or dehydroascorbate, because vitamin C in the plasma becomes oxidized after reacting with radicals that are produced by neutrophils or other cells of the immune system. This maintains plasma ascorbate in its reduced form. This is important because dehydroascorbate competes with glucose for uptake by the "fast track" glucose (GLUT) transport system present in most cells. Hence, the inhibition of glucose uptake by dehydroascorbate would be overcome (23), as shown schematically in Figure 5.

2. There also may be a direct effect of lipoate on the uptake of glucose by the glucose (GLUT) transport system and thus an effect on the insulin-dependent stimulation of glucose uptake. It was of interest to investigate some of those parameters using the skeletal muscle-derived L6 myotube cell culture system. When L6 myoblasts differentiate into myotubes, they gain the ability to take up glucose. Amira Klip's laboratory has reported extensively on this system

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