Cyclooxygenase-2 (PTGS2) inhibitors augment the rate of hexose transport in L6 myotubes in an insulin-and AMPKα-independent manner

E. Alpert, A. Gruzman, B. Lardi-Studler, G. Cohen, R. Reich, S. Sasson

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Aims/hypothesis: Some cyclooxygenase-2 (COX2, also known as prostaglandin-endoperoxide synthase 2 [PTGS2]) inhibitors have been shown to increase insulin sensitivity in man or induce hypoglycaemic episodes when overconsumed or taken in combination with oral hypoglycaemic drugs. These side-effects and their impact on patients are not always recognised in routine clinical practice. We investigated whether these side-effects of COX2 (PTGS2) inhibitors result from stimulation of the glucose transport system in skeletal muscle cells. Materials and methods: L6 myotube cultures were used to study effects of COX2 (PTGS2) inhibitors on the glucose transport system and their relationship to PTGS2 expression, insulin action and AMP-activated protein kinase α (AMPKα) activity. Results: The inhibitors niflumic acid, nimesulide and rofecoxib increased the rate of hexose uptake in L6 myotubes in the absence of insulin and in a dose- and time-dependent manner. They did this by increasing the total cell content of member 4 of the solute carrier family 2 (SCLC2A4, previously known as glucose transporter 4 [GLUT4]) (but not SCLC2A1 [previously known as GLUT1]) mRNA and protein and the amount of it in the plasma membrane. AMPKα was not involved in the latter effect since the inhibitors did not activate it. In addition, none of the inhibitors modulated the rate of hexose transport in vascular endothelial and smooth muscle cells expressing PTGS2 and SCLC2A1. Prostaglandin-endoperoxide synthase 1 (also known as cyclooxygenase 1) inhibitors (acetylsalicylic acid and indomethacin) did not alter the rate of hexose uptake and SCLC2A4 subcellular distribution in L6 myotubes. Conclusions/interpretation: This study suggests that certain COX2 (PTGS2) inhibitors can alter glucose homeostasis in vivo by stimulating glucose uptake in skeletal muscles that express PTGS2.

Original languageEnglish
Pages (from-to)562-570
Number of pages9
JournalDiabetologia
Volume49
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements Preliminary results from this study were presented at the EASD congress in Munich, Germany, in September 2004 [41]. S. Sasson and R. Reich are members of the David R. Bloom Center for Pharmacy, The Hebrew University of Jerusalem. We thank N. Tennagels (Aventis Pharma) for his useful comments and suggestions and R. Blejter for her technical assistance. E. Alpert and A. Gruzman received fellowships from the Hebrew University Center for Diabetes Research. This work was supported by grants from the Chief Scientist of the Israel Ministry of Health, The Yedidut Foundation Mexico and the David R. Bloom Center for Pharmacy.

Keywords

  • Cyclooxygenase inhibitors
  • Diabetes
  • Drug interaction
  • Glucose transport
  • Hypoglycaemia
  • Niflumic acid
  • Nimesulide
  • Rofecoxib
  • Skeletal muscle

Fingerprint

Dive into the research topics of 'Cyclooxygenase-2 (PTGS2) inhibitors augment the rate of hexose transport in L6 myotubes in an insulin-and AMPKα-independent manner'. Together they form a unique fingerprint.

Cite this