Troglitazone enhances differentiation, basal glucose uptake, and Glut1 protein levels in 3T3-L1 adipocytes.
Troglitazone is a member of the thiazolidinedione class of compounds, which act as insulin-sensitizing agents when administered to human patients and animal models displaying noninsulin-dependent diabetes mellitus. In Zucker rats, the antidiabetic activity is associated with increased glucose uptake in adipose tissue. To understand the direct effects troglitazone has on adipocyte metabolism, 3T3-L1 preadipocytes and adipocytes were treated with the compound. The addition of troglitazone enhanced the rate and percent differentiation of fibroblasts to adipocytes. Northern analysis indicated that during differentiation, expression of the adipocyte-specific transcription factor, CCAAT enhancer binding protein-alpha, increased more rapidly in troglitazone-treated cells, but did not change in fully differentiated adipocytes. To assess the metabolic consequences of troglitazone treatment, both basal and insulin-stimulated glucose uptake were monitored in treated cells. Troglitazone treatment increased basal glucose transport 1.5- to 2.0-fold, whereas insulin-stimulated uptake was unaffected. Enhanced basal transport was caused by an increased synthesis of both Glut1 glucose transporter messenger RNA and protein. These results suggest the possibility that in vivo, the troglitazone-dependent increase in glucose disposal may be attributable in part to modification in the expression of Glut1 in insulin-responsive tissues.
Department of Cell Biology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co., Ann Arbor, Michigan 48105, USA. Tafuris@aa.wl.com
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014158:Transcription, Genetic / Q000187:drug effects; D000077288:Troglitazone
D002839:Chromans; D051272:Glucose Transporter Type 1; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; C495678:Slc2a1 protein, mouse; C495679:Slc2a1 protein, rat; D013844:Thiazoles; D045162:Thiazolidinediones; D003609:Dactinomycin; D003847:Deoxyglucose; D000077288:Troglitazone; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine