Discovery of the mechanism that connects low testosterone with diabetes could lead to better treatments for men as they age.
A new study explains why men with low levels of testosterone are at increased risk for type 2 diabetes (T2D), and it could lead to better treatment.
The study, published in Cell Metabolism, shows for the first time that testosterone deficiency decreases insulin production, according to Franck Mauvais-Jarvis, MD, PhD, of Tulane University’s School of Medicine.
Tests done with mice revealed that those bred without the androgen receptor for testosterone all developed lower insulin secretion, which led to glucose intolerance relative to a control group of mice fed the same diet, but who had the androgen receptor.
“We have found the cause—and a potential treatment pathway—for type 2 diabetes in testosterone deficient men,” said Mauvais-Jarvis, senior author on the paper.
“Our study shows that testosterone is an anti-diabetic hormone is men. If we can modulate its action without side effects, it is a therapeutic avenue for type 2 diabetes,” he said.
The findings have important implications, because testosterone in men often drops after age 40, and these men are at greater risk for developing T2D. The findings confirm what physicians have seen on their own—if they treat low testosterone, it improves diabetic status.
To gain greater understanding of the mechanism, researchers conducted a comparative experiment: they administered testosterone and glucose directly onto a set of human pancreatic islet cells that had been treated with an androgen receptor inhibitor, as well as a set of murine islet cells without androgen receptors.
In both sets, the islet cells displayed decreased insulin production compared to islet cells whose receptor to testosterone was not inhibited or missing.
Another experiment with both murine and human islet cells showed that testosterone’s insulin-producing effects were blocked by inhibiting glucagon-like peptide-1 (GLP-1), which is already on the market as a diabetes therapy.
Navarro G, Xu W, Jacobson DA, et al. Extranuclear actions of the androgen receptor enhance glucose-stimulated insulin secretion in the male [published online April 28, 2016]. Cell Metab. 2016; DOI: http://dx.doi.org/10.1016/j.cmet.2016.03.015