Effects of hormone therapy on insulin signaling proteins in skeletal muscle of cynomolgus monkeys.
Level 5 - mechanism / opinion, no new human data
Animal experimental study (non-human primates).
PubMed 15219409 · doi:10.1016/j.steroids.2004.02.002
What was done
Ovariectomized cynomolgus monkeys were treated for 2 years across three groups: no hormones (n = 10), conjugated equine estrogens alone (CEE, 0.625 mg/day human equivalent, n = 11), or CEE plus medroxyprogesterone acetate (MPA, 2.5 mg/day human equivalent, n = 12). Biopsies of the rectus femoris muscle were obtained at basal and insulin-stimulated (10 minutes post-intravenous insulin injection) states. Immunoblotting measured protein expression of insulin receptor, IRS-1, IRS-2, PI 3-kinase p85 subunit, and GLUT4, as well as insulin receptor tyrosine phosphorylation.
What was found
Animals receiving CEE + MPA showed significantly reduced skeletal muscle GLUT4 expression (ANOVA P = 0.001). Treatment had no significant effect on protein expression of insulin receptor, IRS-1, IRS-2, or the p85 subunit of PI 3-kinase. Insulin receptor tyrosine phosphorylation displayed a non-significant trend toward reduction with CEE + MPA (ANOVA P = 0.14). Specific baseline and post-treatment protein concentrations or percentage changes were not reported in the abstract.
Why it matters
These findings suggest that down-regulation of skeletal muscle GLUT4 expression may be a primary cellular mechanism underlying the whole-body insulin resistance observed with combined estrogen and progestin hormone therapy.
Limits
The study evaluated a non-human primate model with small group sizes (n = 10–12 per arm). Downstream signaling kinases such as Akt, direct measures of functional glucose transport, and absolute protein quantification values were not reported in the abstract.
Cited by
- supports Progesterone induces hyperinsulinemia, acts on the pancreas and liver, and antagonizes GLUT4 receptor translocation in skeletal muscle to deposit body fat.