9-deoxy-delta-9-prostaglandin-d2 and Hypoglycemia

The insulin sensitizing thiazolidinedione drugs, rosiglitazone and pioglitazone are specific peroxisome proliferator-activated receptor-gamma agonists and reduce pro-inflammatory responses in patients with type 2 diabetes and coronary artery disease, and may be beneficial in sepsis. Sepsis was induced in 8-10-wk-old C57BL/6 mice by cecal ligation and puncture (CLP) with a 22 -g double puncture technique. Mice received an i.p. injection of vehicle (DMSO:PBS) or pioglitazone (20 mg/kg) at 1 h and 6 h after CLP, and were sacrificed at various time points. In sepsis, vehicle-treated mice had hypoglycemia, increased lung injury and increased lung neutrophil infiltration. Pro-inflammatory plasma cytokines were increased, but the plasma adipokine, adiponectin, was decreased in vehicle-treated septic mice. This corresponded with inhibitor κB (IκBα) protein degradation and an increase in NF-κB activity in lung. Pioglitazone treatment improved plasma Glc and adiponectin levels, and decreased pro-inflammatory cytokines. Lung IκBα protein expression increased and corresponded with a decrease in NF-κB activity in the lung from pioglitazone-treated mice. Pioglitazone reduces the inflammatory response in polymicrobial sepsis in part through inhibition of NF-κB and may be a novel therapy in sepsis.

Topics: Adipokines; Animals; Cytokines; Hypoglycemia; Hypoglycemic Agents; I-kappa B Proteins; Inflammation; Lung; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Pioglitazone; PPAR gamma; Prostaglandin D2; Sepsis; Thiazolidinediones