Effects of hormone therapy on insulin signaling proteins in skeletal muscle of cynomolgus monkeys

Steroids
Melanie K ShadoanJanice D Wagner

Abstract

We have previously shown that hormone therapy (HT) with medroxyprogesterone acetate (MPA) alone or in combination with conjugated equine estrogens (CEE) impairs insulin sensitivity. In the current study, we sought to determine if the effect of MPA on whole body insulin sensitivity is associated with alterations in insulin signaling proteins in skeletal muscle. Ovariectomized cynomolgus monkeys were treated for 2 years with either no hormones (n = 10), CEE (0.625 mg/day human equivalent, n = 11) or CEE + MPA (2.5 mg/day human equivalent, n = 12). At the end of the study, biopsies of rectus femoris muscle were flash frozen in the basal and insulin-stimulated (10 min post-intravenous insulin injection) state. Immunoblotting revealed that CEE + MPA monkeys had significantly less glucose transporter 4 (GLUT4) expression (ANOVA P = 0.001), but there was no significant treatment effect on expression of insulin receptor, insulin receptor substrate (IRS)-1, IRS-2, or the p85 subunit of phosphatidylinositol 3-kinase (PI 3-K). There was a tendency for decreased insulin receptor tyrosine phosphorylation with CEE + MPA treatment (ANOVA P = 0.14). These deficiencies in skeletal muscle insulin signaling likely contribute to the unfavorable ch...Continue Reading

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Citations

Jun 29, 2006·ILAR Journal·Janice E WagnerJay R Kaplan
Jun 17, 2008·Metabolism: Clinical and Experimental·Janice D WagnerMichael R Adams
May 22, 2007·Metabolism: Clinical and Experimental·Melanie K ShadoanJanice D Wagner
Jan 22, 2011·Metabolism: Clinical and Experimental·Patrick A RoweJanice D Wagner
Apr 17, 2021·Journal of Diabetes Research·Xiu WangWeina Hu

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