Estrogens stimulate endothelial cells to improve insulin delivery, a key discovery in battle against type 2 diabetes
In addition to their classic reproduction functions, estrogens have a powerful impact on glucose homeostasis.
In rodents and female primates, ovariectomy causes glucose intolerance and insulin resistance, especially in the context of diet -induced obesity, but these effects are reversed with these hormones.
In this sense, the UT Southwestern Medical Center scientists team discovered that this hormone stimulates cells that cover blood vessels to administer insulin to the muscles, which reduces blood sugar and protects against type 2 diabetes.
The findings, published in Nature Communications, could eventually lead to new therapies for this ailment, a disease that affects hundreds of millions of people worldwide and that continues to increase their prevalence.It is that this study in mice revealed a new mechanism that improves insulin delivery to the muscles, where 80% of body glucose is eliminated.
It has long known that estrogen seems to protect against type 2 diabetes, a disease characterized by high levels of blood sugar, or glucose, caused by a loss of insulin action in the body organs that control theblood sugar.For example, women who pass through natural menopause or enter this state through surgery to remove estrogen producers have a significantly higher risk of type 2 diabetes than premenopausalHormonal replacement.
Similarly, men with mutations that inactivate estrogen receptors, which mediate their action in cells, also are more likely to develop this condition.Although the metabolic effects of estrogen on muscle and adipose tissue have been well documented in the past, their effect on endothelial cells, which cover blood vessels, were unknown.For more information, it was decided to study mice in which the estrogen receiver was selectively eliminated from endothelial cells through a genetic technique.
Like humans who carry a mutation of the estrogen receptor, male mice with this alteration developed a form of type 2 diabetes. In the female to which the ovaries were removed and followed a diet rich in fats, the selective silencingFrom the estrogen receptor gene in endothelial cells it resulted in a complete loss of estrogen antidiabetic actions.
These works showed that in both sexes, the estrogen receiver plays a fundamental role in endothelial cells to reduce blood glucose.Other cultivation cell experiments showed that when estrogen stimulates receptors in endothelial cells, insulin is easily transported from one side to the other.In mice, this effect caused the movement of insulin from the bloodstream to the skeletal muscle, which consumes the vast majority of body glucose.
A closer look showed that a protein known as classifying nexin 5 (SNX5) plays a key role in this process.The researchers verified that the use of a genetic technique to deactivate this protein in endothelial cells caused the same loss of estrogen capacity to stimulate insulin transport as the elimination of estrogen receptors.
Together, these findings indicate that both in men and women, the action of estrogen on endothelial cells isCriticism to bring insulin to skeletal muscles, where it reduces glucose.More work is needed to determine where estrogen comes from the transport of insulin to the muscles in men.By taking advantage of these mechanisms, scientists will eventually develop new therapies to treat type 2 diabetes.
*Philip Shaul, study leader, Pediatrics professor and director of the Pediatric Center for Pulmonary and Vascular Biology in UT Southwestern.
