Elevation of cyclic AMP levels in mouse embryonic stem cells by insulin related peptides.
The preimplantation mammalian embryo has been shown to respond to exogenous insulin-like growth factors and insulin itself, however, the most quantitatively important source of these peptides and the receptors through which they exert their effects are unclear. Whilst the type 1 insulin-like growth factor (IGF) receptor is believed to act primarily through tyrosine phosphorylation of the substrate protein alpha IRS-1, evidence for a signalling role for the type 2 receptor is disputed, some evidence pointing to mediation through G protein-dependent calcium ion flux. We have examined the response of murine embryonic stem cells, as a model for the cells of the preimplantation embryo, to IGF-I, IGF-II, insulin and analogs of IGF-II: R6 IGF-II and des (1-6) IGF-II. In response to all of these peptides, except R6 IGF-II, elevation of intracellular cyclic AMP occurs. As R6 IGF-II binds with higher affinity to the type 2 receptor than canonical IGF-II or IGF-I, and insulin fails to interact, this suggests that the elevation of cyclic AMP in response to the other insulin related peptides (IRPs) is not through the type 2 receptor. We conclude that either the type 1 receptor has a previously uncharacterized direct or indirect effect on intracellular cyclic AMP levels, or that there is a further, as yet uncharacterized, receptor active in embryonic stem cells.
Parkin
M D
MD
Department of Anatomy, University of Cambridge, UK.
McNulty
S
S
Schofield
P N
PN
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D004622:Embryo, Mammalian / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D005260:Female; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D011247:Pregnancy; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D017527:Receptor, IGF Type 2 / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D011972:Receptor, Insulin / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*
D007328:Insulin; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D000242:Cyclic AMP; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D002118:Calcium