We’ve seen that Tetrahymena cells cannot exist in a sea of food unless the start-up concentration exceeds 100 ml/cells. While these data suggest Tetrahymena produces some type of growth factor that is endogenously synthesized and secreted, might something produced by a multicellular organism be able to substitute for this protozoan growth factor?

Below are the results from an experiment conducted by Søren Christensen’s lab (1):

The data shown in (A) are cells that are added to media. Note that a starting concentration of 400 and 40 cells/ml leads to cell death, but at 4000 cells/ml, you see growth of the population. The data in (B) show growth at all starting concentrations. So what is different? The researchers simply added human insulin in (B). We’ve seen that mammalian insulin enhances cell division in Hydra and plants, thus, as we would expect from a front-loading perspective, human insulin also can substitute for a Tetrahymena growth factor and stimulate cell survival and division. In fact, insulin appears to function in two different realms of concentration. Here is an excerpt from the study:

Insulin stimulates cell survival and activates proliferation in a biphasic manner at low initial cell densities of T. thermophila in conical culture flasks: at 400 cells/ml it activates proliferation in two separate intervals; down to nanomolar concentrations and again in the low pico- and femtomolar range. The reasons for this pattern are unknown but it is possible that the biphasic response may be due to receptors with different affinity states for insulin as described for insulin receptors in mammalian cell systems (for ref. see Gammeltoft, 1984). If this is true, then the effects of insulin observed at about 10-14 M may be brought about via receptors with a very high affinity to insulin or insulin-related material. One might also construe that the biphasic response may be due to events of an inhibitory/ desensitization action between separate receptor systems. Thus, like e.g. glucagon in hepatocytes (Housley et al., 1987), insulin or insulin-related material in T. thermophila may act through two functionally and presumably structurally distinct receptor populations, which we here call ILR1 and ILR2. ILR1 may be activated in order to stimulate proliferation down to about 10-7 M and inhibit the activity of ILR2 down to about 10-11 M. ILR1 may not be activated at lower concentrations and insulin induces cell survival and proliferation through the activation of ILR2 at about 10-11–10-14 M.

Insulin has some other interesting effects on Tetrahymena cells and we’ll look at these next time.

1. Figure from Søren T. Christensen, Helene Quie, Kåre Kemp And Leif Rasmussen. 1996. Insulin Produces A Biphasic Response In Tetrahymena Thermophila By Stimulating Cell Survival And Activating Proliferation In Two Separate Concentration Intervals. Cell Biology International 20: 437–444.