Effects of 17β-Estradiol and Androgen on Glucose Metabolism in Skeletal Muscle.

Autor:	Inada A; Laboratory of Molecular Life Science (A.I., Y.N.), Institute of Biomedical Research and Innovation, Kobe 650-0047, Japan; Department of Diabetes and Genes (A.I., O.I.), Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Health Promotion Sciences (N.L.F.), Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan; and Faculty of Sports and Health Science (Y.H.) and Institute for Physical Activity (Y.H.), Fukuoka University, Fukuoka 814-0180, Japan., Fujii NL; Laboratory of Molecular Life Science (A.I., Y.N.), Institute of Biomedical Research and Innovation, Kobe 650-0047, Japan; Department of Diabetes and Genes (A.I., O.I.), Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Health Promotion Sciences (N.L.F.), Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan; and Faculty of Sports and Health Science (Y.H.) and Institute for Physical Activity (Y.H.), Fukuoka University, Fukuoka 814-0180, Japan., Inada O; Laboratory of Molecular Life Science (A.I., Y.N.), Institute of Biomedical Research and Innovation, Kobe 650-0047, Japan; Department of Diabetes and Genes (A.I., O.I.), Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Health Promotion Sciences (N.L.F.), Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan; and Faculty of Sports and Health Science (Y.H.) and Institute for Physical Activity (Y.H.), Fukuoka University, Fukuoka 814-0180, Japan., Higaki Y; Laboratory of Molecular Life Science (A.I., Y.N.), Institute of Biomedical Research and Innovation, Kobe 650-0047, Japan; Department of Diabetes and Genes (A.I., O.I.), Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Health Promotion Sciences (N.L.F.), Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan; and Faculty of Sports and Health Science (Y.H.) and Institute for Physical Activity (Y.H.), Fukuoka University, Fukuoka 814-0180, Japan., Furuichi Y; Laboratory of Molecular Life Science (A.I., Y.N.), Institute of Biomedical Research and Innovation, Kobe 650-0047, Japan; Department of Diabetes and Genes (A.I., O.I.), Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Health Promotion Sciences (N.L.F.), Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan; and Faculty of Sports and Health Science (Y.H.) and Institute for Physical Activity (Y.H.), Fukuoka University, Fukuoka 814-0180, Japan., Nabeshima YI; Laboratory of Molecular Life Science (A.I., Y.N.), Institute of Biomedical Research and Innovation, Kobe 650-0047, Japan; Department of Diabetes and Genes (A.I., O.I.), Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Health Promotion Sciences (N.L.F.), Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan; and Faculty of Sports and Health Science (Y.H.) and Institute for Physical Activity (Y.H.), Fukuoka University, Fukuoka 814-0180, Japan.
Jazyk:	angličtina
Zdroj:	Endocrinology [Endocrinology] 2016 Dec; Vol. 157 (12), pp. 4691-4705. Date of Electronic Publication: 2016 Sep 21.
DOI:	10.1210/en.2016-1261
Abstrakt:	Diabetes develops predominantly in males in experimental models, and extensive evidence suggests that 17β-estradiol (E2) modulates progression of diabetes in humans. We previously developed a severely diabetic transgenic (Tg) mouse model by β-cell-specific overexpression of inducible cAMP early repressor (ICER) and found that male ICER-Tg mice exhibit sustained severe hyperglycemia, but female ICER-Tg mice gradually became normoglycemic with aging. This implies that differences in circulating androgen and E2 levels might influence skeletal muscle glucose uptake and glycemic status. Here we examined whether a decrease of androgen or E2 excess can improve muscle glucose uptake in hyperglycemic male ICER-Tg mice and, conversely, whether a decrease of E2 or androgen excess can elevate blood glucose levels and impair muscle glucose uptake in normoglycemic female ICER-Tg mice. We treated hyperglycemic male ICER-Tg mice with orchiectomy (ORX) or ORX+E2 pellet implantation and normoglycemic female ICER-Tg mice with ovariectomy (OVX) or OVX+5α-DHT pellet implantation to alter the androgen to E2 ratio. ORX+E2 treatment of male ICER-Tg mice caused a rapid drop in blood glucose via both a dramatic increase of β-cells and significantly improved muscle glucose uptake due to the induction of glucose transporter type 4 (GLUT4) expression and translocation of GLUT4 to the cell membrane. In contrast, OVX+5α-DHT-treated female ICER-Tg mice showed an elevation of blood glucose without any decrease of β-cells; instead, they showed decreased muscle glucose uptake due to decreased activation of serine/threonine-specific protein kinase AKT and GLUT4 expression. These findings suggest that androgen (5α-DHT) promotes insulin resistance in females, whereas E2 improves insulin sensitivity in severely diabetic male mice.
Databáze:	MEDLINE
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