| Insulin is known to decrease apolipoprotein B (apoB) secretion in various hepatic models, an observation that is thought to be mediated through the phosphatidylinositol 3-kinase (PI3K) pathway. To investigate whether the insulin inhibition on apoB secretion involves molecules downstream of PI3K, we overexpressed a downstream kinase, Akt/PKB. Overexpression of activated Akt did not affect apoB levels as shown by immunoblotting and radiolabelling experiments in hepatic cell lines McArdle RH-7777 or HepG2. To test the involvement of the mitogen-activated protein kinase (MAPK) pathway in the insulin effect, the MAPK kinase, MEK, was inhibited using chemical inhibitors in HepG2 cells. Blocking the MAPK pathway alone decreased cellular and secreted apoB, and the insulin effect was blocked in MEK-inhibited cells. Therefore, the insulin effect on apoB appears to involve molecules upstream of Akt in the PI3K pathway, and apoB may be regulated by the MAPK pathway with a mechanism independent from insulin. |
