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Acute effects of troglitazone and nitric oxide on glucose uptake in L929 fibroblast cells

David A Van Dyke1, Lindsey Walters, Deborah Frieswyk

  • 1Department of Chemistry and Biochemistry, Calvin College, 3201 Burton S.E., Grand Rapids, MI 49546, USA.

Life Sciences
|March 18, 2003
PubMed

Insights

Troglitazone and nitric oxide acutely increase glucose uptake in cells, suggesting a shared pathway independent of calcium. This research highlights novel mechanisms for glucose transport regulation via GLUT 1 transporters.

Area of Science:

  • Cell Biology
  • Pharmacology
  • Metabolism

Background:

  • Thiazolidinediones, like troglitazone, are antidiabetic drugs with insulin-sensitizing effects.
  • Troglitazone exhibits acute insulin-independent glucose uptake stimulation in certain tissues.
  • Nitric oxide is known to promote glucose uptake in peripheral muscle tissue.

Purpose of the Study:

  • To investigate the acute, insulin-independent effects of troglitazone on glucose uptake.
  • To explore the role of nitric oxide in modulating glucose uptake in L929 fibroblast cells.
  • To elucidate the signaling pathways involved in troglitazone- and nitric oxide-mediated glucose uptake.

Main Methods:

  • Measuring 2-deoxyglucose (2DG) uptake in L929 fibroblast cells.
  • Utilizing troglitazone and the nitric oxide donor sodium nitroprusside (SNP) as stimulants.
  • Employing the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) and dantrolene to probe signaling pathways.

Main Results:

  • Troglitazone dose-dependently stimulated 2DG uptake (>300% at 5-10 microM).
  • SNP significantly increased 2DG uptake (>200% at 5 mM).
  • Combined stimulant effects were not additive, suggesting a shared pathway, but L-NMMA did not inhibit troglitazone's effect, indicating convergence after nitric oxide production. Dantrolene had no impact, ruling out calcium involvement.

Conclusions:

  • Troglitazone and nitric oxide acutely stimulate glucose uptake via distinct but converging pathways.
  • These effects on glucose transport are independent of intracellular calcium levels.
  • The findings provide evidence for acute regulation of glucose transport mediated by GLUT 1 transporters.

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