Researchers have a viewpoint that estrogen, a female hormone, has the potential to decrease the insulin resistance and control the blood glucose. The new study proving this point is published in the journal named Diabetes.
Metabolic Effect of Estrogen
The motivation behind pursuing this research was an observational study that was previously conducted and had accidentally discovered a link between menopause and a reduced incidence of diabetes type 2.
Moreover, various animal and clinical studies have established a strong association between the deficiency of estrogen and an increase in metabolic disorders.
Postmenopausal women tend to show increased insulin sensitivity and a reduced prevalence of diabetes type 2, as compared to men of equivalent age. However, this advantage tends to vanish once a woman hits her menopausal age. That is when her glucose homeostasis gets disrupted, particularly due to the reduction in the levels of estrogen in the blood.
However, the research has not been able to indicate the mechanism that allows these connections to get established.
Moreover, using estrogen as a potential treatment for diabetes type 2 and other metabolic dysfunctions without any proper understanding of the mechanisms can lead to serious side effects. For example, diseases like blood clots, heart attacks, breast cancer, and stroke are the most common problems that often occur due to estrogen therapy.
This is why it is very important to develop an understanding of the tissue-specific action of estrogen and the mechanisms involved in its metabolic regulation. Once the scientists understand this mechanism, it will help in the development of the estrogen mimics which may provide therapeutic benefits without causing any side effects.
The Role of Foxo1 in Metabolic Effects of Estrogen
In this new study, the scientists set out to understand the links by which estrogen tends to regulate gluconeogenesis by interacting with hepatic Foxo1, a gene also known as forkhead box O1.
Gluconeogenesis can be described as a process through which glucose is synthesized. This gene encodes a certain transcription factor or a protein that can activate or deactivate other types of genes.
Foxo1 is considered as the primary target of insulin signaling that regulates the metabolic homeostasis in the body as a response to the oxidative stress. It also carries an important role in the regulation of glucose generation with the help of insulin signaling. It is also an important component of the cascades of insulin signaling that help regulate growth, differentiation, and metabolism of the cells.
In order to investigate the role of this gene and how it reacts with estrogen, the researchers studied female mice with no ovaries, normal male mice, and male and female mice in which Foxo1 gene had been removed from the liver.
The researchers utilized a subcutaneous implant that was releasing estrogen in the mice. This implant was found to improve the insulin sensitivity and suppress gluconeogenesis in the male mice in addition to the female mice with no ovaries.
However, it did not affect the mice in which the Foxo1 gene was not present. This indicates that this gene is essential for estrogen to suppress the process of gluconeogenesis.