Effect of sodium salicylate on oxidative stress and insulin resistance induced by free fatty acids.
BACKGROUND
It has been reported that high-dose salicylates improve free fatty acids (FFAs)-induced insulin resistance and beta-cell dysfunction in vitro, but the mechanism remains uncertain. In insulin-resistant rats, we found that the supplementation of sodium salicylate is associated with a reduction of plasma malondialdehyde (MDA), a marker of oxidative stress. Few studies have investigated the effects of salicylates on oxidative stress levels in insulin-resistant animal models. This study aimed to assess the effect of sodium salicylate on insulin sensitivity and to explore the potential mechanism by which it improves hepatic and peripheral insulin resistance.


METHODS
Intralipid+heparin (IH), saline (SAL), or intralipid+heparin+sodium salicylate (IHS) were separately infused for 7 hours in normal Wistar rats. During the last 2 hours of the infusion, hyperinsulinemic-euglycemic clamping was performed with [6-3H] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassay. MDA levels and glutathione peroxidase (GSH-PX) activity in the liver and skeletal muscle were measured with colorimetric kits.


RESULTS
Compared with infusion of SAL, IH infusion increased hepatic glucose production (HGP), and decreased glucose utilization (GU) (P<0.05). The elevation of plasma free fatty acids increased the MDA levels and decreased the GSH-PX activity in the liver and muscle (P<0.01). Sodium salicylate treatment decreased HGP, elevated GU (P<0.05), reduced MDA content by 60% (P<0.01), and increased the GSH-PX activity by 35% (P<0.05).


CONCLUSIONS
Short-term elevation of fatty acids induces insulin resistance by enhancing oxidative stress levels in the liver and muscle. The administration of the anti-inflammatory drug sodium salicylate reduces the degree of oxidative stress, therefore improving hepatic and peripheral insulin resistance. IKK-beta and NF-kappaB provide potential pathogenic links to oxidative stress.
He
Bing
B
Department of Endocrinology, Shengjing Affiliated Hospital, China Medical University, Shenyang 110004, China.
Zhao
Sheng
S
Zhang
Wei
W
Li
Yan
Y
Han
Ping
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000009:adverse effects* / Q000097:blood; D005947:Glucose / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012980:Sodium Salicylate / Q000008:administration & dosage / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008315:Malondialdehyde; D006493:Heparin; D005979:Glutathione Peroxidase; D005947:Glucose; D012980:Sodium Salicylate