How Does Estrogen Help in Controlling Type 2 Diabetes?

Type 2 Diabetes is one of the most important health problems all over the world.

About 84 million people in the United States live with prediabetes, a condition where blood sugar levels are very high but not high enough to warrant a diagnosis of type 2 diabetes.

Usually, prediabetes occurs in people with insulin resistance – a condition in which cells in some vital organs do not respond well to insulin and therefore do not absorb enough glucose from the blood.

A Hormone That May Reduce Insulin Resistance and Glucose Production

Are there?

Researchers believe that estrogen has the potential to do this, thereby reducing the prevalence of type 2 diabetes.

Currently, more than 100 million people in the United States live with diabetes or prediabetes, and estimates suggest that more than 30 million adults have type 2 diabetes.

Shaodong Guo, associate professor of Nutrition and Food Science at Texas A&M University, College Station, led the new research. The study was published in Diabetes, the journal of the American Diabetes Association.

You can reach our article for estrogen and other female hormones.

Why Should We Study the Metabolic Effect of Estrogen?

Guo explains the motivation for the study, saying that previous observational research has revealed less of a link between the incidence of type 2 diabetes and premenopausal women.

Also, clinical and animal studies have found a strong link between estrogen deficiency and metabolic disorders.

“Premenopausal women show increased insulin sensitivity and a reduced incidence of type 2 diabetes compared with age-equivalent men,” Guo said. “However, this advantage disappears after menopause with impaired glucose homeostasis, in part due to reduced circulating estrogen.”

However, researchers have yet to elucidate the mechanisms responsible for these links.

Also, estrogen-blind use as a potential treatment for type 2 diabetes and other prediabetes metabolic dysfunctions can cause serious side effects. For example, stroke, breast cancer, blood clots, and heart attack are some of the health risks associated with estrogen therapy.

“This is why it is so important to understand the tissue-specific effect of estrogen and its molecular mechanism in metabolic regulation,” Guo said.

“Once this mechanism is understood, it will aid in the development of targeted estrogen mimics that could provide therapeutic benefits without the unwanted side effects.”

Foxo1 Mediates Estrogen Metabolic Effects

In the new study, the researchers “wanted to understand the mechanism by which estrogen regulates gluconeogenesis by interacting with hepatic Foxo1,” cited the lead researcher for a gene also called forklift box O1.

Gluconeogenesis describes the synthesis process by which glucose is produced.

The Foxo1 gene encodes a transcription factor or a type of protein that helps activate or deactivate other genes.

“Foxo1” is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress, the US National Library of Medicine reports.

As Guo explains, “Foxo1 has an important role in regulating glucose production through insulin signaling. It is an essential component of insulin signaling cascades that regulate cellular growth, differentiation, and metabolism.”

To investigate the role of the gene and how it interacts with estrogen, the researchers studied male mice, ovariectomized female mice, and both male and female mice whose Foxo1 genes were transplanted in the liver.

The researchers used an estrogen-secreting subcutaneous implant in mice. This implant improved “insulin sensitivity and suppressed gluconeogenesis” in male mice as well as ovariectomized female mice.

However, the implant did not affect rodents with knocked out liver-specific Foxo1 genes. “This suggests that Foxo1 should be effective at suppressing gluconeogenesis for estrogen,” Guo explained.

“We also showed that estrogen suppresses hepatic glucose production through activation of estrogen receptor signaling, which may be independent of the insulin receptor substrates Irs1 and Irs2.”

“This reveals an important mechanism for estrogen in regulating glucose homeostasis,” says Guo. The beneficial effects of estrogen on glucose homeostasis may be controlled by liver-specific Foxo1-mediated gluconeogenesis, rather than promoting glucose uptake into the muscles.

Therapeutic and Dietary Effects of Estrogen in Type 2 Diabetes

Guo explained the therapeutic implications of the findings: “Identification of the tissue-specific effects of estrogen and direct targets of estrogen receptors will facilitate the development of new selective ligands that prevent obesity without promoting type 2 diabetes, cardiovascular disease, and abnormal sex characteristics or breast cancer.”

Finally, the researcher also commented on the dietary results of the study. Some foods, such as soybeans, tofu, and miso soup, contain phytoestrogens that can have the same beneficial effects on metabolic health.

“It provides a fundamental understanding that dietary intervention can play an important role in controlling obesity, diabetes, and related chronic diseases,” says Guo.

“Investigated the role of estrogen in the control of glucose homeostasis, which has a profound impact on our understanding of obesity and diabetes, as well as potential dietary interventions.”

Shaodong Guo, Ph.D.

MedicalNewsToday, How can estrogen help control type 2 diabetes?, 2019

Reference

https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/prediabetes-insulin-resistance

https://www.cdc.gov/media/releases/2017/p0718-diabetes-report.html

http://diabetes.diabetesjournals.org/content/early/2018/11/21/db18-0638

https://www.nhlbi.nih.gov/files/docs/pht_facts.pdf

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