In situ phosphorylation of akt and ERK1/2 in rat mammary gland, colon, and liver following treatment with human insulin and IGF-1

Henning Hvid; Johannes J. Fels; Rikke K. Kirk; Inger Thorup; Henrik Michael Elvang Jensen; Bo F.  Hansen; Martin B.  Oleksiewicz

doi:10.1177/0192623311406936

In situ phosphorylation of akt and ERK1/2 in rat mammary gland, colon, and liver following treatment with human insulin and IGF-1

Henning Hvid, Johannes J. Fels, Rikke K. Kirk, Inger Thorup, Henrik Michael Elvang Jensen, Bo F. Hansen, Martin B. Oleksiewicz

14 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Toxicologic Pathology
Vol/bind	39
Udgave nummer	4
Sider (fra-til)	623-640
Antal sider	18
ISSN	0192-6233
DOI	https://doi.org/10.1177/0192623311406936
Status	Udgivet - jun. 2011

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10.1177/0192623311406936

https://journals.sagepub.com/doi/pdf/10.1177/0192623311406936

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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.",

author = "Henning Hvid and Fels, {Johannes J.} and Kirk, {Rikke K.} and Inger Thorup and Jensen, {Henrik Michael Elvang} and Hansen, {Bo F.} and Oleksiewicz, {Martin B.}",

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TY - JOUR

T1 - In situ phosphorylation of akt and ERK1/2 in rat mammary gland, colon, and liver following treatment with human insulin and IGF-1

AU - Hvid, Henning

AU - Fels, Johannes J.

AU - Kirk, Rikke K.

AU - Thorup, Inger

AU - Jensen, Henrik Michael Elvang

AU - Hansen, Bo F.

AU - Oleksiewicz, Martin B.

PY - 2011/6

Y1 - 2011/6

N2 - 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.

AB - 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.

U2 - 10.1177/0192623311406936

DO - 10.1177/0192623311406936

M3 - Journal article

C2 - 21558470

SN - 0192-6233

VL - 39

SP - 623

EP - 640

JO - Toxicologic Pathology

JF - Toxicologic Pathology

IS - 4

ER -

In situ phosphorylation of akt and ERK1/2 in rat mammary gland, colon, and liver following treatment with human insulin and IGF-1

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