title: Thrombospondin 1 Suppresses Insulin Signaling in C2C12 Myotubes.
abstract: Thrombospondin 1 (TSP-1) is abundantly expressed in visceral adipose tissue and this expression is up-regulated in obese humans and rodents. Recent studies showed that genetic deletion of TSP-1 protects mice from diet-induced insulin resistance. However, the molecular mechanism is largely unknown. In this study, we examined the effect of recombinant TSP-1 on insulin signaling in cultured cells from insulin sensitive tissues to investigate whether TSP-1 could act as an adipokine. Here we show that treatment with recombinant TSP-1 suppressed insulin signaling in cultured muscle cells, which was accompanied by the activation of stress signaling such as JNK, p38, and IKK. These results suggest that TSP-1 acts as an adipokine which is involved in the pathogenesis of obesity-induced insulin resistance. Thus, TSP-1 could be a potential target for the treatment of insulin resistance and metabolic disease related to insulin resistance.
authors: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors: Kaku
authors: K
authors: Matsugi
authors: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors: Tetsuya
authors: T
authors: Hosooka
authors: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors: Kazuhiro
authors: K
authors: Nomura
authors: Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors: Wataru
authors: W
authors: Ogawa
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D054392:Adipokines; D007328:Insulin; D011994:Recombinant Proteins; D019700:Thrombospondin 1; C585483:Thbs1 protein, mouse
keywords: IKK; Insulin resistance; JNK; Obesity; Thrombospondin 1; p38