Troglitazone prevents the inhibitory effects of inflammatory cytokines on insulin-induced adipocyte differentiation in 3T3-L1 cells.
Tumor necrosis factor (TNF) is implicated in wasting syndromes and insulin resistance in chronic infection and obese-linked diabetes. TNF (10 ng/ml) inhibited adipocyte differentiation of 3T3-L1 cells, and in these TNF treated cells little insulin-stimulated glucose uptake was observed. Treatment of 3T3-L1 cells with troglitazone (1-10 microM) partially prevented this inhibitory effect of TNF on adipogenesis, and enhanced expression of C/EBP alpha and GLUT4, even in the presence of TNF. Troglitazone also prevented the inhibitory effects of interleukin-1, interleukin-6, and leukemia inhibitory factor, but not of transforming growth factor beta on adipocyte differentiation of 3T3-L1 cells. These effects might contribute to the antidiabetic effect of troglitazone in obese diabetic animals.
Ohsumi
J
J
Biomedical Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan.
Sakakibara
S
S
Yamaguchi
J
J
Miyadai
K
K
Yoshioka
S
S
Fujiwara
T
T
Horikoshi
H
H
Serizawa
N
N
D016475:3T3 Cells / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D017667:Adipocytes / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D004347:Drug Interactions; D005786:Gene Expression Regulation; D005947:Glucose / Q000493:pharmacokinetics; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000235:genetics; D009124:Muscle Proteins; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001786:Blood Glucose; D002839:Chromans; D016207:Cytokines; D051275:Glucose Transporter Type 4; D007328:Insulin; D007375:Interleukin-1; D015850:Interleukin-6; D008222:Lymphokines; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse; D013844:Thiazoles; D045162:Thiazolidinediones; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C010598:leukocyte inhibitory factor; D000077288:Troglitazone; D005947:Glucose