ANTIDIABETIC AGENT PIOGLITAZONE ENHANCES ADIPOCYTE DIFFERENTIATION OF3T3-F442A CELLS

Adipocytes play an important role in normal physiology as a major site for systemic energy homeostasis. In disorders such as diabetes, adipo cyte function is markedly altered. In this study, we investigated the effect of pioglitazone, a novel antidiabetic agent known to lower plas ma glucose in animal models of diabetes mellitus, on cellular differen tiation and expression of adipose-specific genes. Treatment of conflue nt 3T3-F442A preadipocyte cultures for 7 days with pioglitazone (Pio; 1 muM) and insulin (Ins; 0.17 muM) resulted in >95% cell differentiati on into lipid-accumulating adipocytes in comparison with 60-80% cell d ifferentiation by treatment with either agent alone. Analysis of trigl yceride accumulation showed increases of triglyceride content over tim e above untreated preadipocytes by treatment of the cells with Ins, Pi o, and especially with Ins + Pio. Basal glucose transport, as measured by cellular uptake of 2-deoxy-D-[C-14]glucose, was likewise enhanced in a time-dependent manner by treatment of preadipocytes with Ins, Pio , or Ins + Pio, such that a synergistic effect resulted from the combi ned treatment with both agents. It was further determined that RNA tra nscript abundance for genes encoding glucose transporters GLUT-1 and G LUT-4, as well as the adipose-specific genes encoding adipsin and aP2, were increased by the Ins, Pio, or Ins + Pio treatment. Taken togethe r, these findings indicate that pioglitazone is a potent adipogenic ag ent. By promoting differentiation, this agent may move cells into a st ate active for glucose uptake, storage, and metabolism.