| dc.description.abstract | Insulin, insulin-like growth factor (IGF)-I and -II, and (−)-epigallocatechin gallate (EGCG) have been reported to regulate fat cell functions. However, it is still not clear how EGCG acts on insulin and IGFs signaling pathways for stimulating mitogenesis and glucose uptake in fat cells. The first chapter indicated that EGCG suppressed insulin-stimulated phosphorylation of the insulin receptor-β, insulin receptor (IR) substrates 1 and 2 (IRS1 and IRS2), and MAPK pathway proteins, RAF1, MEK1/2, and ERK1/2, but not JNK. EGCG inhibited the association of IR with the IRS1 and IRS2 proteins, but not with the IRS4 protein. These data suggest that EGCG selectively affects particular types of IRS and MAPK family members. EGCG tended to increase insulin-stimulated associations between the 67LR and IR, IRS1, IRS2, and IRS4 proteins. These data suggest that EGCG mediates anti-insulin signaling in preadipocyte mitogenesis via the 67LR pathway. The second chapter indicated that EGCG suppressed IGF-I-stimulated and IGF-II-stimulated phosphorylation of p66Shc and MAPK pathway proteins, including RAF1, MEK1, and ERK1/2, but not JNK, protein kinase B, p52Shc, or p46Shc. Furthermore, we demonstrated that EGCG mediates anti-IGF-I and anti-IGF-II signals in preadipocyte mitogenesis via the 67LR but not the AMPK pathway. The third chapter indicated that EGCG inhibited IGF-I and IGF-II stimulation of adipocyte glucose uptake. The 67LR mediated the effect of EGCG on IGF-stimulated glucose uptake in adipocytes. EGCG suppressed the IGF-stimulated phosphorylation of PKCζ/λ, but not Akt or ERK, proteins. EGCG inhibited IGF stimulation of 3T3-L1 adipocyte glucose uptake through downregulated GLUT4 translocation and IGF signaling by the 67LR- and AMPK-dependent pathways. Results of this dissertation would help explain the mechanisms of how EGCG regulates insulin-, IGF-I-, and IGF-II-mediated actions on fat cells and how it exerts its antiobese effect.
| en_US |