Insulin sensitization of MAP kinase signaling by fibroin in insulin-resistant Hirc-B cells.
Fibroin has been shown to enhance insulin-stimulated glucose uptake in 3T3-L1 adipocytes, and the mechanism underlying the fibroin effect focused on phosphatidylinositol 3-kinase (PI 3-K) pathway has been reported. In the present study, for defining the insulin-sensitizing effects of fibroin synthetically, we have used the Hirc-B cells which are rat fibroblasts over-expressing wild-type human insulin receptors to investigate the insulin-stimulation of mitogen-activated protein (MAP) kinase signaling cascades. Cultivation of Hirc-B cells in high-glucose medium for 6 days led to an insulin-resistant state in which insulin-stimulated DNA synthesis was blocked completely. Chronic exposure to fibroin for 16 h markedly recovered DNA synthesis in insulin-resistant cells. Development of insulin resistance caused a reduction of c-Jun N-terminal kinase (JNK) phosphorylation, which was also recovered by fibroin exposure. Fibroin sensitized the insulin-stimulated c-Jun accumulation and phosphorylation in insulin-resistant cells. In the time course for c-Jun accumulation, fibroin had a vanadate-like effect. Further, fibroin was shown to delay the degradation of c-Jun. It is suggested that fibroin may sensitize insulin action by blocking JNK dephosphorylation caused by MAP kinase phosphatase-1 (MKP-1).
Graduate School of Life Science, Handong Global University, Pohang, Kyungbuk 791-708, Republic of Korea.
Kum-Ju
KJ
Park
Eun-Jung
EJ
Shin
So-Hui
SH
Kim
Chang-Kee
CK
Hyun
D000818:Animals; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005349:Fibroins / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D007328:Insulin; D016755:Proto-Oncogene Proteins c-jun; D005349:Fibroins; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases