Studies on growth-promoting action of insulin: mitogenic activity of insulin and its analogues in mouse mammary tumor cells.
Growth-promoting action of insulin and its analogues was studies in the mouse mammary tumor cell line GR2H6 by measuring 3H-thymidine incorporation. The mitogenic activity of the analogues obtained by shortening of C-terminus of insulin B chain decreased with stepwise removal of terminal residues, and [A3Leu]insulin was approximately 1000 times less potent than insulin. However, the despentapeptide (B26-B30) insulin(DPI) showed a strikingly higher mitogenic activity at high concentrations; the detected maximal effect of DPI was 136% more than that of insulin. These results demonstrate that the C-terminal area of the B chain and the N-terminal alpha-helix of the A chain are important for the mitogenic activity of insulin. A region corresponding to the growth-promoting function of insulin and a model of DPI action are proposed and discussed.
Shi
M
M
State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry, Chinese Academy of Sciences, China.
Feng
Y M
YM
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D007328:Insulin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D013552:Swine; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D007328:Insulin; C048031:insulin, Leu(A3)-