Pro-oxidant challenge in vivo provokes the onset of NIDDM in the insulin resistant obese Zucker rat

We investigated the ability of an acute pro-oxidant challenge in vivo to de teriorate glycaemic control and insulin action in the obese Zucker rat, a m odel of insulin resistance associated with oxidant stress. In obese animals , the daily administration for 1 week of hydroquinone (HQ) in combination w ith L-buthionine sulphoximine (BSO), elevated fasting plasma glycaemia and insulinaemia and markedly aggravated i.v. glucose-stimulated hyperinsulinae mia without significantly affecting i.v. glucose tolerance, suggesting exac erbated insulin resistance. Intermediate effects on hyperinsulinaemia in ob ese animals were determined with HQ treatment alone while BSO treatment alo ne had no effect. In contrast, none of the pro-oxidant treatments affected age-matched, insulin sensitive, lean Zucker rats. Our data therefore demons trate for the first time, a vulnerability to deterioration in insulin actio n in an established insulin resistant state following an environmental pro- oxidative insult. This may have relevance in the conversion of insulin resi stance syndrome (IRS) to non-insulin dependent diabetes mellitus (NIDDM).