{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:46:32Z","timestamp":1778827592129,"version":"3.51.4"},"reference-count":63,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>Diabetes develops predominantly in males in experimental models, and extensive evidence suggests that 17\u03b2-estradiol (E2) modulates progression of diabetes in humans. We previously developed a severely diabetic transgenic (Tg) mouse model by \u03b2-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+5\u03b1-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 \u03b2-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+5\u03b1-DHT-treated female ICER-Tg mice showed an elevation of blood glucose without any decrease of \u03b2-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 (5\u03b1-DHT) promotes insulin resistance in females, whereas E2 improves insulin sensitivity in severely diabetic male mice.<\/jats:p>","DOI":"10.1210\/en.2016-1261","type":"journal-article","created":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T18:17:37Z","timestamp":1474481857000},"page":"4691-4705","source":"Crossref","is-referenced-by-count":29,"title":["Effects of 17\u03b2-Estradiol and Androgen on Glucose Metabolism in Skeletal Muscle"],"prefix":"10.1210","volume":"157","author":[{"given":"Akari","family":"Inada","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Life Science (A.I., Y.N.), Institute of Biomedical Research and Innovation, Kobe 650-0047, Japan;"},{"name":"Department of Diabetes and Genes (A.I., O.I.), Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuharu L.","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Health Promotion Sciences (N.L.F.), Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oogi","family":"Inada","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Genes (A.I., O.I.), Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuki","family":"Higaki","sequence":"additional","affiliation":[{"name":"Faculty of Sports and Health Science (Y.H.), Fukuoka University, Fukuoka 814-0180, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuro","family":"Furuichi","sequence":"additional","affiliation":[{"name":"Institute for Physical Activity (Y.H.), Fukuoka University, Fukuoka 814-0180, 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