title: Insulin receptor-deficient cells as a new tool for dissecting complex interplay in insulin and insulin-like growth factors.
abstract: Cell systems derived from knockout mice for the insulin receptor (IR) or the IGF-1 receptor (IGF-1R) represent unique tools for dissecting complex interplay in the actions of insulin and insulin-like growth factors through their cognate versus non-cognate receptor. In this study, we used a fibroblast cell line derived from IR-deficient mice to investigate metabolic and mitogenic effects of IGF-1 and insulin. IGF-1 was able to stimulate glucose uptake, glucose incorporation into glycogen and thymidine incorporation in such cells. Phosphatidylinositol 3-kinase and mitogen-activated protein kinase, two enzymes of major metabolic-mitogenic signaling pathways, were activated upon stimulating these cells with IGF-1. All these effects were also achieved when IR-deficient cells were stimulated with insulin. Thus, IGF-1R can represent an alternative receptor through which insulin might exert some of its effects.
authors.affiliation: Institut Cochin de Génétique Moléculaire, INSERM U257, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Lamothe
authors.forename: A
authors.initials: A
authors.lastname: Baudry
authors.forename: C T
authors.initials: CT
authors.lastname: Christoffersen
authors.forename: P
authors.initials: P
authors.lastname: De Meyts
authors.forename: J
authors.initials: J
authors.lastname: Jami
authors.forename: D
authors.initials: D
authors.lastname: Bucchini
authors.forename: R L
authors.initials: RL
authors.lastname: Joshi
mesh_terms: D000818:Animals; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000378:metabolism; D011972:Receptor, Insulin / Q000172:deficiency* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
chemical_list: D007328:Insulin; D008934:Mitogens; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D013936:Thymidine