Biol. Pharm. Bull. 28(11) 2040—2045 (2005)

sue components such as bone, cartilage, the hematopoietic supporting stroma and adipocytes. Among cell types, the adipocytes are perhaps the most abundant stromal cell phenotype in adult human bone marrow. Generally, adipocytes play an important role in systemic lipid metabolism and also contribute to adiposity, insulin resistance and atherogenesis. Gimble et al. have reviewed the function of bone marrow adipocytes and proposed four hypotheses: (1) a passive role, simply occupying excess space in the bone marrow cavity; (2) an active role in systemic lipid metabolism; (3) a localized energy reservoir in the bone marrow; (4) direct contribution to the promotion of hematopoiesis and an influence on osteogenesis. However, the function of adipocytes in bone marrow is still controversial. The stromal cell line MC3T3-G2/PA6 (PA6) was established from mouse clavaria as preadipocytes having the capacity to convert to mature adipose cells. Greenberger reported that corticosteroids accumulated lipids in primary cultured mammalian bone marrow preadipocytes, but insulin did not. In addition, the adipogenesis in PA6 cells is also markedly accelerated by the addition of dexamethasone, but insulin is not required for the process. Insulin is a major hormone controlling critical energy functions such as glucose and lipid metabolism. Its effects result from insulin binding to a membrane receptor (insulin receptor), which is expressed highly on insulin target tissues, such as the liver, muscles and adipocytes. The binding leads to its receptor autophosphorylation and then to tyrosine phosphorylation of substrate proteins, such as insulin receptor substrates (IRSs). These allow for the formation of macromolecular complexes close to the receptor. The two main transduction pathways are the phosphatidylinositol 3kinase (PI3K) pathway and the mitogen-activated protein kinase (MAPK) pathway. The MAPK pathway is considered to be involved in nuclear effects, proliferation and differentiation, while the PI3K pathway plays a major role in insulin functions, mainly via activation of the Akt cascade. Activation of Akt stimulates glycogen synthesis, protein synthesis, cell survival, inhibition of lipolysis, and glucose uptake. However, nothing is known about insulin signaling in bone marrow adipocytes, which are unresponsive to insulin in the adipogenesis process. Therefore, we assessed insulin signaling and its functions, such as glucose uptake and the inhibition of lipolysis, in adipocytes differentiated from bone marrow preadipocyte PA6 cells.