It has been reported that high-dose
salicylates, an IKKss inhibitor, may prevent FFAs-induced
insulin resistance. In previous study, we found that in FFAs-induced
insulin resistant rats, administration of
salicylate was associated with a reduction of plasma
malondialdehyde (MDA). In the present study, we investigated the effects of
sodium salicylate on FFAs-induced
insulin resistance and on oxidative stress in liver. Overnight-fasted Wistar rats were subject to 7h i.v. infusion of either saline or
Intralipid plus 20U/ml
heparin (IH) with or without
salicylate. Hyperinsulinemic-euglycemic clamp with tracer infusion was performed to assess
insulin-induced suppression of endogenous
glucose production (EGP). Oxidative
antioxidant markers, immunohistochemical
inducible nitric oxide synthase (iNOS)
stain,
nitric oxide (NO), MDA,
Superoxide dismutase (SOD) activity in liver was measured. Infusion of IH markedly decreased
insulin-induced suppression of EGP, which were completely prevented by
salicylate co-infusion. Furthermore,
salicylate reversed IH-induced (1) increase in iNOS and NO expression in the liver; (2) increase in MDA/SOD in the liver. This study provides preliminary assessments of efficacy of
sodium salicylate as a new treatment for FFAs-induced
insulin resistances. The effect of increasing
insulin sensitivity by
salicylate in part may be secondary to reduce the oxidative stress in liver.