Type 2 diabetes affects hundreds of millions of people worldwide, and the incidence rate is still rising. In a new study, researchers from the University of Texas Southwestern Medical Center reported that the typical female sex hormone estrogen can stimulate vascular endothelial cells to deliver insulin to muscles, thus reducing blood sugar and preventing type 2 diabetes. This discovery may eventually lead to new treatments for type 2 diabetes. The relevant research results have recently been published in the journal Nature Communications, with the title of the paper being "Endothalial ER α Promotes glucose tolerance by enhancing endothermic insulin transport to skeletal muscle.
Philip Shaul, M.D., a professor of pediatrics and director of the Center for Pediatric Pulmonary and Vascular Biology at the University of Texas Southwest Medical Center and co author of the paper, said, "This study on mice reveals a new mechanism that enhances insulin delivery to muscles, where 80% of the body's glucose is processed
Scientists have long known that estrogen seems to prevent type 2 diabetes, a disease characterized by high blood sugar, caused by the loss of insulin function in the body organ that controls blood sugar.
For example, the risk of type 2 diabetes in women who enter menopause after natural menopause or through surgical removal of estrogen producing ovaries is significantly higher than that in premenopausal women, and this risk can usually be reduced through hormone replacement therapy. Similarly, the estrogen receptor, which regulates the role of estrogen in cells, mutates and becomes inactive, making men more susceptible to this disease.
Although the metabolic effects of estrogen on muscle and adipose tissue have been fully demonstrated, its impact on vascular endothelial cells is still unknown. In order to learn more information, Dr. Shaul and his colleagues conducted a study on mice, selectively removing estrogen receptors from vascular endothelial cells through genetic technology. Like humans carrying estrogen receptor mutations, male mice with this change developed rodent type 2 diabetes.
In female mice with ovariectomy and high-fat diet (in healthy mice, estrogen treatment can reverse type 2 diabetes), selective silencing of estrogen receptor gene in vascular endothelial cells leads to complete loss of estrogen's anti diabetic effect. These experiments indicate that estrogen receptors play a crucial role in reducing blood sugar in the endothelial cells of male and female mice.
Further experiments conducted in cultured vascular endothelial cells in vivo have shown that when estrogen stimulates estrogen receptors on the surface of vascular endothelial cells, insulin is easily transferred from one side of these cells to the other. In mice, this effect causes insulin to enter skeletal muscle from the blood, which consumes the majority of glucose in the body.
Scientists have long known that estrogen seems to prevent type 2 diabetes, a disease characterized by high blood sugar, caused by the loss of insulin function in the body organ that controls blood sugar.
For example, the risk of type 2 diabetes in women who enter menopause after natural menopause or through surgical removal of estrogen producing ovaries is significantly higher than that in premenopausal women, and this risk can usually be reduced through hormone replacement therapy. Similarly, the estrogen receptor, which regulates the role of estrogen in cells, mutates and becomes inactive, making men more susceptible to this disease.
Although the metabolic effects of estrogen on muscle and adipose tissue have been fully demonstrated, its impact on vascular endothelial cells is still unknown. In order to learn more information, Dr. Shaul and his colleagues conducted a study on mice, selectively removing estrogen receptors from vascular endothelial cells through genetic technology. Like humans carrying estrogen receptor mutations, male mice with this change developed rodent type 2 diabetes.
In female mice with ovariectomy and high-fat diet (in healthy mice, estrogen treatment can reverse type 2 diabetes), selective silencing of estrogen receptor gene in vascular endothelial cells leads to complete loss of estrogen's anti diabetic effect. These experiments indicate that estrogen receptors play a crucial role in reducing blood sugar in the endothelial cells of male and female mice.
Further experiments conducted in cultured vascular endothelial cells in vivo have shown that when estrogen stimulates estrogen receptors on the surface of vascular endothelial cells, insulin is easily transferred from one side of these cells to the other. In mice, this effect causes insulin to enter skeletal muscle from the blood, which consumes the majority of glucose in the body.
Endothelial ER α Does not affect insulin induced recruitment of capillaries in skeletal muscle. Image from Nature Communications, 2023, doi: 10.1038/s41467-023-40562-w.
After careful observation, it was found that a protein called sorting nexin 5 (SNX5) played a crucial role in this process. These authors found that using genetic technology to turn off this protein in vascular endothelial cells can lead to the loss of estrogen's ability to stimulate insulin transport, which is similar to the effect of removing estrogen receptors.
Dr. Shaul said that these findings collectively indicate that the effect of estrogen on vascular endothelial cells is crucial for delivering insulin to skeletal muscles, whether in female or male mice, where insulin can reduce glucose. Further research is needed to determine where the estrogen that promotes insulin transport to muscles in males comes from. He said that through the use of mechanisms conducive to insulin transport in vascular endothelial cells, scientists may eventually develop new treatments for type 2 diabetes.
Dr. Shaul said that these findings collectively indicate that the effect of estrogen on vascular endothelial cells is crucial for delivering insulin to skeletal muscles, whether in female or male mice, where insulin can reduce glucose. Further research is needed to determine where the estrogen that promotes insulin transport to muscles in males comes from. He said that through the use of mechanisms conducive to insulin transport in vascular endothelial cells, scientists may eventually develop new treatments for type 2 diabetes.
