p42/p44 Mitogen-Activated Protein Kinases Activation Is Required for the Insulin-Like Growth Factor-I/Insulin Induced Proliferation, but Inhibits Differentiation, in Rat Fetal Brown Adipocytes

Almudena Porras, Alberto M. Álvarez, Amparo Valladares, Manuel Benito
1998 Molecular Endocrinology  
Insulin-like growth factor I (IGF-I)/insulin induced cytosolic p42/p44 mitogen-activated protein kinase (MAPK) activation in a time-dependent manner in fetal brown adipocytes, reaching a maximum at 5 min. Concurrently, nuclear p42/p44 MAPKs were also activated by IGF-I and insulin. This cytosolic and nuclear MAPK activation was totally prevented by pretreatment with the MAPK kinase (MEK1) inhibitor, PD98059. These results indicate that MEK mediates the IGF-I/insulin-induced p42/ p44 MAPK
more » ... ion. IGF-I and insulin also increased the number of cells in the S؉G 2 /M phases of the cell cycle, PCNA levels, and DNA synthesis at 24 h. This IGF-I/insulin-induced proliferation was completely blunted by the presence of MEK1 inhibitor. In contrast, inhibition of MEK1 potentiated the IGF-I-induced uncoupling protein (UCP-1) and the insulin-induced fatty acid synthase mRNAs expression after short and long-term treatments. Moreover, transient expression of a transfected active MEK construct (R4F) decreased IGF-I-induced UCP-1 and insulin-induced fatty acid synthase mRNA expression. These results demonstrate that p42/p44 MAPKs are essential intermediates for the IGF-I/insulin-induced mitogenesis, but may have a negative role in the regulation of adipocytic and thermogenic differentiation in brown adipocytes.
doi:10.1210/mend.12.6.0122 pmid:9626658 fatcat:qwk4jepbnbfitizr7idt7dcjga