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

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Abstract
The direct short‐term effects of troglitazone on parameters of glucose metabolism were investigated in rat soleus muscle strips. 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−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. 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−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. No differences between troglitazone and hypoxia were identified in respective interactions with insulin. 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.