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Updated: Nov 8, 2025

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
Virilizing doses of testosterone decrease circulating insulin levels and differentially regulate insulin signaling in
Kadden H Kothmann1, Victoria Jacobsen1, Emily Laffitte1
1Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas.
Testosterone therapy in transgender men may lead to insulin resistance by suppressing circulating insulin and altering insulin signaling pathways in white adipose tissue. This study in female pigs reveals testosterone
Area of Science:
- Endocrinology
- Metabolic Research
- Translational Medicine
Background:
- Transgender men on testosterone therapy face potential risks of insulin resistance.
- The precise impact of virilizing testosterone on insulin levels and sensitivity in transgender men remains unclear.
- Female pigs serve as a translational model to investigate these effects.
Purpose of the Study:
- To assess the acute effects of virilizing testosterone on serum insulin concentrations.
- To examine insulin signaling pathways in key metabolic tissues (liver, skeletal muscle, white adipose tissue).
- To provide insights into potential mechanisms of insulin resistance in transgender men.
Main Methods:
- Female pigs received intramuscular testosterone cypionate or a control vehicle.
- Blood samples were collected serially to measure hormone and metabolite levels.
- Tissue analysis (liver, skeletal muscle, white adipose tissue) was performed at the study's end.
Main Results:
- Virilizing testosterone concentrations were associated with decreased serum insulin and C-peptide levels.
- Testosterone upregulated insulin-signaling pathway components in the liver but suppressed signaling in white adipose tissue.
- Altered protein phosphorylation in white adipose tissue suggests impaired insulin sensitivity.
Conclusions:
- Acute exposure to virilizing testosterone suppresses circulating insulin and alters insulin signaling in metabolic tissues.
- Downregulation of insulin signaling in white adipose tissue may contribute to insulin resistance.
- Findings suggest potential mechanisms for insulin resistance observed in transgender men undergoing hormone therapy.
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