Insulin but not IGF-I is required for the maintenance of the adipose phenotype in the adipogenic cell line 1246 |
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Authors: | Ginette Serrero Nancy Lepak |
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Institution: | (1) Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy and Program of Oncology, Marlene and Stewart Greenebaum Cancer Center of the University of Maryland, 21201-1180 Baltimore, Maryland;(2) Present address: Trudeau Institute, 12983 Saranac Lake, New York |
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Abstract: | Summary The mouse adipogenic cell line 1246 which possesses both insulin and insulin-like growth factor I (IGF-I) receptors was used
to investigate the role of IGF-I and insulin on the proliferation of adipocyte precursors and their differentiation into mature
adipocytes. Results indicate that both insulin and IGF-I stimulate the proliferation of the 1246 adipocyte precursors with
IGF-I being slightly more potent than insulin. Dose-response studies indicated that both polypeptides acted at physiological
concentrations corresponding to binding to their own receptors. In contrast, comparison of insulin and IGF-I capacity to stimulate
terminal adipose differentiation indicated that only insulin was active when added at physiological concentrations. IGF-I
could not stimulate adipocyte differentiation except at supraphysiological concentrations (100 ng/ml and above) permitting
its binding to the insulin receptors on 1246 cells. Time course study of expression of early and late markers of adipose differentiation
indicated that the induction of markers such as adipose differentiation-related protein (ADRP), lipoprotein lipase (LPL) and
fatty acid binding protein (FAB) took place even in the absence of insulin. However, the level of early and late differentiation
markers decreased to a level below the one found in undifferentiated cells when cells had been maintained in the absence of
insulin after differentiation had been initiated. These data indicate that although insulin is not necessary for the early
onset of the adipose differentiation program, it is stringently required for the maintenance of the adipocyte phenotype and
cannot be substituted by IGF-I. |
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Keywords: | proliferation adipose differentiation adipocyte adipocyte precursors insulin insulin-like growth factor I |
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