Insulin and Insulin-Like Growth Factors Stimulate Deoxyribonucleic Acid Synthesis in PC 12 Pheochromocytoma Cells

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Abstract
The effects of insulin and insulin-like growth factors (IGFs) on the replication of PC12 pheochromocytoma cells were investigated. Incubation of PC12 cells for 2-3 days in low (0.3%) serum medium decreased [3H]thymidine incorporation into PC12 cell DNA to approximately 30% of that in control (15% serum) medium. Incubation of the cells in low serum medium also slowed the growth of the cultures and increased the percentage of cells in the G0/G1 phase of the cell cycle. Addition of insulin to cells in low serum medium increased [3H]thymidine incorporation into the cells, increased the number of cells in PC12 cultures, and decreased the percentage of cells in the G0/G1 phase of the cell cycle. IGF-I and IGF-II also increased [3H]thymidine incorporation into PC12 cells incubated in low serum medium. IGF-I (EC50, .apprx. 0.3 nM) was a more potent stimulus of [3H]thymidine incorporation than was insulin (EC50, .apprx. 3.5 nM). These data suggest that insulin and IGFs are growth factors for PC12 cells, and that the growth-promoting effects of these agents may be mediated by a type I IGF receptor on PC12 cells.