In Situ Phosphorylation of Akt and ERK1/2 in Rat Mammary Gland, Colon, and Liver Following Treatment with Human Insulin and IGF-1

• Published in: Toxicologic pathology 2011-06, Vol.39 (4), p.623-640
• Main Authors: Hvid, Henning, Fels, Johannes J., Kirk, Rikke K., Thorup, Inger, Jensen, Henrik E., Hansen, Bo F., Oleksiewicz, Martin B.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Breast - cytology; Breast - drug effects; Colon - drug effects; Epithelial Cells - drug effects; Female; Humans; Immunohistochemistry; Insulin - pharmacology; Insulin-Like Growth Factor I - pharmacology; Liver - drug effects; Mammary Glands, Animal - drug effects; Medical sciences; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Receptor, IGF Type 1 - metabolism; Signal Transduction - drug effects; Toxicology
• ISSN: 0192-6233; 1533-1601
• DOI: 10.1177/0192623311406936

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.