title: In situ phosphorylation of Akt and ERK1/2 in rat mammary gland, colon, and liver following treatment with human insulin and IGF-1.
abstract: High doses of insulin and the insulin analog AspB10 have been reported to increase mammary tumor incidence in female rats likely via receptor-mediated mechanisms, possibly involving enhanced IGF-1 receptor activation. However, insulin and IGF-1 receptor functionality and intracellular signaling in the rat mammary gland in vivo is essentially unexplored. The authors investigated the effect of a single subcutaneous dose of 600 nmol/kg human insulin or IGF-1 on Akt and ERK1/2 phosphorylation in rat liver, colon, and mammary gland. Rat tissues were examined by Western blotting and immunohistochemistry by phosphorylation-specific antibodies. Insulin as well as IGF-1 caused Akt phosphorylation in mammary epithelial cells, with myoepithelial and basal epithelial cells being most sensitive. IGF-1 caused stronger Akt phosphorylation than insulin in mammary gland epithelial cells. Phosphorylation of ERK1/2 was not influenced by insulin or IGF-1. Rather, in liver and mammary gland P-ERK1/2 appeared to correlate with estrous cycling, supporting that ERK1/2 has important physiological roles in these two organs. In short, these findings supported that the rat mammary gland epithelium expresses functional insulin and IGF-1 receptors and that phosphorylation of Akt as well as ERK1/2 may be of value in understanding the effects of exogenous insulin in the rat mammary gland and colon.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Denmark. hhvd@novonordisk.com
authors.forename: Henning
authors.initials: H
authors.lastname: Hvid
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Fels
authors.forename: Rikke K
authors.initials: RK
authors.lastname: Kirk
authors.forename: Inger
authors.initials: I
authors.lastname: Thorup
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Jensen
authors.forename: Bo F
authors.initials: BF
authors.lastname: Hansen
authors.forename: Martin B
authors.initials: MB
authors.lastname: Oleksiewicz
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001940:Breast / Q000166:cytology / Q000187:drug effects; D003106:Colon / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D008321:Mammary Glands, Animal / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3