Oxidative stress may be involved in the development of vascular complications associated with diabetes; however, the molecular mechanism responsible for increased production of free radicals in diabetes remains uncertain. Therefore, we examined whether acute hyperinsulinemia increases the production of free radicals and whether this condition affects proliferative extracellular signal؊regulated kinase (ERK-1 and -2) signaling in human fibroblasts in vitro. Insulin treatment significantly increased intracellular superoxide anion (O 2 ؊ ) production, an effect completely abolished by Tiron, a cell-permeable superoxide dismutase (SOD) mimetic and by polyethylene glycol (PEG)-SOD, but not by PEG catalase. Furthermore, insulin-induced O 2 ؊ production was attenuated by the NAD(P)H inhibitor apocynin, but not by rotenone or oxypurinol. Inhibition of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway with LY294002 blocked insulin-stimulated O 2 ؊ production, suggesting a direct involvement of PI 3-kinase in the activation of NAD(P)H oxidase. The insulininduced free radical production led to membranous translocation of p47phox and markedly enhanced ERK-1 and -2 activation in human fibroblasts. In conclusion, these findings provided direct evidence that elevated insulin levels generate O 2 ؊ by an NAD(P)H-dependent mechanism that involves the activation of PI 3-kinase and stimulates ERK-1؊ and ERK-2؊dependent pathways. This effect of insulin may contribute to the pathogenesis and progression of cardiovascular disease in the insulin resistance syndrome. Diabetes 53

The sign of the exchange interaction J in a series of radical triplet pairs (RTPs), formed by a nitroxide free radical and a triplet excited fullerene, has been determined from the spin polarization of time-resolved electron paramagnetic resonance spectra. Radical and fullerene are linked together by covalent bonds in different geometries. It is shown that the sign of J depends on the overlap between the orbital of nitroxide unpaired electron and the LUMO of fullerene, which is singly occupied in the excited triplet state. When the overlap does not vanish, a negative contribution to J arises from the admixing of a charge transfer structure in the wave function of the excited doublet state D of the RTP, which does not take place in the excited quartet state Q. The mixing of D* and Q' states lowers the energy of the former spin state and gives antiferromagnetic coupling.

Chronic AZT administration increases blood pressure and promotes cardiovascular damage through a NAD(P)H oxidase-dependent mechanism that involves PKC delta. Vitamin C antagonizes these adverse effects of AZT in the cardiovascular system.

The magnitude and sign of the electron exchange interaction J between two nitroxide radicals in a series of [60]fullerene bisadducts (trans‐4 bisadduct shown) have been measured. The J value correlates with the distance between and the relative orientation of the unpaired electron molecular orbitals.

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