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Updated: Jun 27, 2026

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Selective COX2 inhibition improves whole body and muscular insulin resistance in fructose-fed rats
1Department of Physiology & Biophysics, National Defence Medical Centre, Taipei, Taiwan. pshsieh@hotmail.com
Background:
The effects of cyclooxygenase-1 (COX1) and cyclooxygenase-2 (COX2) inhibition on insulin resistance in subjects with the metabolic syndrome remain elusive. Aims of this study were to examine the effects of COX1 and COX2 inhibitors on whole body and muscular insulin resistance in fructose-fed rats, an animal model of the metabolic syndrome.
Materials And Methods:
The rats on regular or 60% fructose-enriched diets for 6 weeks were further divided into rats combined with or without piroxicam (a selective COX1 inhibitor) or celecoxib (a selective COX2 inhibitor) treatment for an additional 2 weeks. Euglycaemic hyperinsulinaemic clamp (EHC) with a tracer dilution method was performed at the end of the study.
Results:
The present result showed that fructose-induced increases in systolic blood pressure and fasting plasma insulin levels were significantly suppressed in rats treated with celecoxib but not piroxicam. In the EHC period, celecoxib significantly reversed fructose-induced decreases in whole body glucose uptake, mainly by glucose storage. Hepatic glucose production and whole body glycolysis were not significantly changed among groups. Celecoxib but not piroxicam significantly reversed fructose-induced decreases in glycogen synthase activities in red and white quadriceps muscles and insulin-stimulated membrane GLUT4 recruitment in soleus muscles. Celecoxib and piroxicam both significantly diminished fructose-induced increases in plasma thromboxane B2 and 6-keto prostaglandin (PG) F1alpha; but only celecoxib treatment significantly attenuated a fructose-induced increase in 8-isoprostane levels. Plasma PGE metabolites were not different among groups.
Conclusions:
This study demonstrates that a therapeutic dose of celecoxib, but not piroxicam, could significantly attenuate fructose-induced whole body and muscular insulin resistance in rats.
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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