Regulation of the cell cycle by insulin and IGF1
Author: Pierre De Meyts, MD, PHD, F.A.C.E.
An increase in the number of cells growing in cell culture is the result of two opposing effects: an increase in the number of cells that traverse the cell cycle and divide into two daughter cells (mitosis), or a decrease in the number of cells that die, principally through programmed cell death (apoptosis), or both.
In this section we will review the mechanisms that control the cell cycle, while apoptosis will be discussed in another section.
Human serum contains two sets of growth factors that function synergistically to promote cell growth through the G0-G1 traverse. “Competence factors” such as platelet-derived growth factor or fibroblast growth factor commit cells to enter the division cycle and render them competent to respond to “progression factors” such as IGF-I (or its substitute insulin at high concentrations). These observations, together with others, suggest that insulin has a “permissive” role that is additive to other growth factors.
IGFs and insulin regulate the cell cycle inhibitor cyclin G2. Unlike classical cyclins that promote cell cycle progression, cyclin G2 causes cell cycle arrest at the G1/S transition. Cyclin G2 is markedly downregulated by insulin, insulin analogues, IGF-I in L6 myoblasts overexpressing the insulin receptor, and in several other cell types.
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