SELENIUM - POTENT STIMULATOR OF TYROSYL PHOSPHORYLATION AND ACTIVATOROF MAP KINASE

Selenium, an essential biological trace element, is an integral compon ent of several enzymes, and its use as a nutritional supplement has be en popularized recently due to its potential role in low concentration s as an antioxidant and in higher concentrations as an anticancer agen t. Selenium has also been reported to act as an insulin-mimetic agent with regard to normalization of blood glucose levels and regulation of some insulin-mediated metabolic processes. Little work, however, has been done concerning the pathway(s) by which this insulin-mimetic acti on occurs. In this study, we investigated the mechanism by which selen ate exhibits insulin-mimetic properties in two different insulin respo nsive cell types, primary rat hepatocytes and 3T3 L1 adipocytes. We fo und that two proteins associated with the insulin signal cascade, the P-subunit of the insulin receptor and IRS-1, increased in tyrosyl phos phorylation in the presence of selenium. The third identified selenium activated signal protein, MAP kinase, has been implicated not only in the insulin signal transduction pathway but also in other growth fact or-mediated responses. Using an in-gel activity assay for MAP kinase, we demonstrated that both the p42 and p44 MAP kinases are activated wh en either hepatocytes or adipocytes are incubated in the presence of s elenate. In addition to the activation of these specific proteins, we found that selenium also eventually profoundly affected overall tyrosy l phosphorylation. Our results therefore show that selenium not only i ncreased the phosphorylation of proteins identified in the insulin sig nal cascade but also affected the overall phosphorylation state of the cell.