Acute non-insulin-like stimulation of rat muscle glucose metabolism by troglitazone in vitro.
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 micromol 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 micromol 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 micromol 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.
Fürnsinn
C
C
Department of Medicine III, University of Vienna, Austria.
Neschen
S
S
Noe
C
C
Bisschop
M
M
Roden
M
M
Vogl
C
C
Schneider
B
B
Waldhäusl
W
W
D000818:Animals; D002839:Chromans / Q000494:pharmacology*; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D012710:Serum Albumin, Bovine; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D012710:Serum Albumin, Bovine; D000077288:Troglitazone; D005947:Glucose