Selective COX2 inhibition improves whole body and muscular insulin resistance in fructose-fed rats

P-S Hsieh1, H-C Tsai, C-H Kuo

  • 1Department of Physiology & Biophysics, National Defence Medical Centre, Taipei, Taiwan. pshsieh@hotmail.com

Abstract

Insights

Selective COX2 inhibition with celecoxib improved insulin resistance in rats with metabolic syndrome. Piroxicam, a COX1 inhibitor, did not show these benefits, indicating COX2 plays a key role in metabolic dysfunction.

Area of Science:

  • Metabolic Syndrome Research
  • Pharmacology
  • Insulin Resistance Studies

Background:

  • Metabolic syndrome is linked to insulin resistance, but the role of cyclooxygenase (COX) enzymes remains unclear.
  • Investigating COX1 and COX2 inhibition effects on insulin resistance is crucial for understanding metabolic syndrome.

Purpose of the Study:

  • To evaluate the impact of COX1 and COX2 inhibitors on whole-body and muscle insulin resistance.
  • To assess these effects in fructose-fed rats, a model for metabolic syndrome.

Main Methods:

  • Fructose-fed rats were treated with selective COX1 (piroxicam) or COX2 (celecoxib) inhibitors.
  • Euglycemic hyperinsulinemic clamp (EHC) with tracer dilution was used to measure insulin sensitivity.

Main Results:

  • Celecoxib, but not piroxicam, reduced elevated blood pressure and insulin levels in fructose-fed rats.
  • Celecoxib improved whole-body glucose uptake and muscle glycogen synthase activity, reversing fructose-induced insulin resistance.
  • Both inhibitors reduced thromboxane B2 and 6-keto PGF1alpha, but only celecoxib attenuated 8-isoprostane.

Conclusions:

  • Selective COX2 inhibition with celecoxib effectively attenuates fructose-induced whole-body and muscular insulin resistance in rats.
  • COX1 inhibition with piroxicam did not yield similar improvements in insulin sensitivity.

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