STUDIES ON GROWTH-PROMOTING ACTION OF INSULIN - MITOGENIC ACTIVITY OFINSULIN AND ITS ANALOGS IN MOUSE MAMMARY-TUMOR CELLS

Growth-promoting action of insulin and its analogues was studied in th e mouse mammary tumor cell line GR2H6 by measuring H-3-thymidine incor poration. The mitogenic activity of the analogues obtained by shorteni ng of C-terminus of insulin B chain decreased with stepwise removal of terminal residues, and [A3Leu]insulin was approximately 1000 times le ss potent than insulin. However, the despentapeptide(B26-B30) insulin( DPI) showed a strikingly higher mitogenic activity at high concentrati ons; the detected maximal effect of DPI was 136% more than that of ins ulin. These results demonstrate that the C-terminal area of the B chai n and the N-terminal alpha-helix of the A chain are important for the mitogenic activity of insulin. A region corresponding to the growth-pr omoting function of insulin and a model of DPI action are proposed and discussed.