The study could help identify new treatments for type 2 diabetes in the large number of men with low testosterone due to age or prostate cancer therapies, researchers said.
"We have found the cause - and a potential treatment pathway - for type 2 diabetes in testosterone-deficient men," said Franck Mauvais-Jarvis from Tulane University in the US.
"Our study shows that testosterone is an anti-diabetic hormone in men. If we can modulate its action without side effects, it is a therapeutic avenue for type 2 diabetes," said Mauvais-Jarvis.
Researchers used specially bred male mice with pancreatic beta cells lacking the receptor to testosterone (the androgen receptor). They fed them a Western diet rich in fats and sugar and tested their response to glucose.
The mice without androgen receptors all developed lower insulin secretion, leading to glucose intolerance compared with normal mice in the control group, researchers said.
To better understand how testosterone interacted with insulin production within the pancreas, researchers administered testosterone and glucose directly to human islet cells treated with an androgen receptor inhibitor and islets cells harvested from mice without androgen receptors.
In both cases the islet cells showed decreased insulin production compared to islet cells whose receptor to testosterone was not inhibited or missing, researchers said.
Further experiments in cultured mouse and human islet cells showed the insulin-producing effect of testosterone could be abolished by inhibiting glucagon-like peptide-1 (GLP-1), a hormone the body produces after a meal, they said.
The study suggests that testosterone amplifies the islet impact of the hormone, which is currently used as a diabetes treatment, researchers said. The findings were published in the journal Cell Metabolism.

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