Hormonal
Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women by impairing the phosphorylation of protein kinase C-zeta (PKCz) downstream of PI3-kinase, without affecting upstream IRS-1 or mitogenic signaling pathways.
For women with high androgen levels (such as in PCOS), excess testosterone can directly interfere with how fat cells respond to insulin. This happens not by blocking the main insulin signal, but by disrupting a specific downstream step (PKCz) required for glucose uptake. This suggests that managing androgen levels may be crucial for improving insulin sensitivity in these individuals.
We conclude that (1) T, or an androgenic metabolite of T, induces insulin resistance in adipocytes of women, selective for metabolic signaling pathways; (2) this defect is via AR; and (3) the defect in signaling is independent of phosphatidyl-inositol 3-kinase activation and involves impaired phosphorylation of PKCz.
Why this rating
In vitro study using human cells; strong mechanistic evidence but lacks in vivo clinical trial confirmation of the specific pathway in humans.
Source
Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women
A. Corbould · Journal of Endocrinology · 2007
DOI 10.1677/joe.1.07070
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