Acute non-insulin-like stimulation of rat muscle glucose metabolism by troglitazone in vitro

Abstract

1. The direct short-term effects of troglitazone on parameters of glucose metabolism were investigated in rat soleus muscle strips.

2. In muscle strips from Sprague-Dawley rats, troglitazone (3.25 μmol l⁻¹) increased basal and insulin-stimulated glucose transport by 24% and 41%, respectively (P<0.01 each).

3. In the presence of 5 nmol l−1 insulin, stimulation of glucose transport by 3.25 μmol l⁻¹ troglitazone was accompanied by a 36% decrease in glycogen synthesis, while glycolysis was increased (112% increase in lactate production) suggesting a catabolic response of intracellular glucose handling.

4. Whereas insulin retained its stimulant effect on [³H]-2-deoxy-glucose transport in hypoxia-stimulated muscle (by 44%; c.p.m. mg⁻¹ h⁻¹: 852±77 vs 1229±75, P<0.01), 3.25 μmol l⁻¹ troglitazone failed to increase glucose transport under hypoxic conditions (789±40 vs 815±28, NS) suggesting that hypoxia and troglitazone address a similar, non-insulin-like mechanism.

5. No differences between troglitazone and hypoxia were identified in respective interactions with insulin.

6. Troglitazone acutely stimulated muscle glucose metabolism in a hypoxia/contraction-like manner, but it remains to be elucidated whether this contributes to the long-term antidiabetic and insulin enhancing potential in vivo or is to be regarded as an independent pharmacological effect.

Full Text

The Full Text of this article is available as a PDF (379.0 KB).