Insulin but not ICF-I is required for the maintenance of the adipose phenotype in the adipogenic cell line 1246

The mouse adipogenic cell line 1246 which possesses both insulin and insuli n-like growth factor (IGF-I) receptors was used to investigate the role of IGF-I and insulin on the proliferation of adipocyte precursors and their di fferentiation into mature adipocytes. Results indicate that both insulin an d IGF-I stimulate the proliferation of the 1246 adipocyte precursors with I GF-I being slightly more potent than insulin. Dose-response studies indicat ed that both polypeptides acted at physiological concentrations correspondi ng to binding to their own receptors. In contrast, comparison of-insulin an d IGF-I capacity to stimulate terminal adipose differentiation indicated th at only insulin was active when added at physiological concentrations. IGF- I could not stimulate adipocyte differentiation except at supraphysiologica l concentrations (100 ng/ml and above) permitting its binding to the insuli n receptors on 1246 cells. Time course study of expression of early and lat e markers of adipose differentiation indicated that the induction of marker s such as adipose differentiation-related protein (ADRP), lipoprotein lipas e (LPL) and fatty acid binding protein (FAB) took place even in the absence of insulin. However, the level of early and late differentiation markers d ecreased to a level below the one found in undifferentiated cells when cell s had been maintained in the absence of insulin after differentiation had b een initiated. These data indicate that although insulin is not necessary f or the early onset of the adipose differentiation program, it is stringentl y required for the maintenance of the adipocyte phenotype and cannot be sub stituted by IGF-I.