Preventing testosterone signaling in pancreatic beta cells in mice leads to a higher insulin secretion in response to glucose, increasing the risk of type 2 diabetes, according to an article published in the journal Cell Metabolism. The study explains why aging men more often get type 2 diabetes, and suggests that targeting the androgen receptor might protect these men from the disease.
Earlier studies have shown that men with low testosterone levels, a common feature of the aging process, are at increased risk of type 2 diabetes. Previous research has, however, not focused on the androgen receptor, which transmits signals through the male sex hormones testosterone and dihydrotestosterone.
The study, “Extranuclear Actions of the Androgen Receptor Enhance Glucose-Stimulated Insulin Secretion in the Male,” used mice engineered to lack the receptor only in their insulin-producing cells in the pancreas. The mutant mice, along with normal controls, were fed a Western-type diet for nine weeks, and then analyzed with a glucose challenge test.
The mutant mice were found to produce less insulin, both on an empty stomach and after a meal, and had increased blood glucose levels.
To further understand how testosterone affects insulin production, the research team isolated the insulin-producing islet cells from mice and studied them in the lab. The team noted that blocking the androgen receptor with a drug produced the same result as removing the receptor when cells were exposed to glucose. Conversely, treating the cells with dihydrotestosterone activated insulin production after a glucose load.
“We have found the cause — and a potential treatment pathway — for type 2 diabetes in testosterone-deficient men,” said Dr. Mauvais-Jarvis, a Price-Goldsmith professor in the Department of Medicine at Tulane University School of Medicine and senior study author, in a press release. “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.”
Findings also showed that blocking GLP-1, a hormone released when eating and used in diabetes treatment, prevented the insulin-triggering effect of testosterone in both mice and human islets, suggesting that testosterone acts to intensify the effect of GLP-1 on islet cells.