FIGURE 2.

A, schema highlighting conceivable events related to the G-X pathway that is involved in the metabolism of myo-inositol following the activation of MIOX in proximal tubules of the kidney. These steps involved are similar to those described in the eye lens. At four different steps of the G-X pathway, perturbations in NADPH/NADP⁺ and NAD⁺/NADH ratios are seen with the anticipated altered cellular redox, akin to the polyol pathway that is accentuated during hyperglycemia in the diabetic state (27, 28) (adapted from Ref. 28 with permission). B–D, expression of G-X pathway enzymes in the kidney. By immunohistochemistry, protein expression of MIOX and ALR1 is seen in identical regions of renal proximal tubules (B and C). No expression is seen in kidney glomeruli (arrowheads). By RT-PCR analyses, expression of other enzymes of the G-X pathway (i.e. gulonate dehydrogenase, xylulose reductase, and xylulose kinase) is demonstrated in kidney tissues (D), thus confirming the existence of the G-X pathway in kidney tubules.