Research from Texas A&M University published in the journal 'Diabetes', provide insights into the mechanism by which estrogen can decrease insulin resistance and the production of glucose, reducing the incidence of type 2 diabetes mellitus. "In this study, we investigated the role of estrogen in control of glucose homeostasis, which has a profound impact on our understanding of obesity and diabetes as well as potential dietary interventions," said Dr. Shaodong Guo, primary study investigator and Texas A&M AgriLife Research scientist in the department of nutrition and food science in College Station.

Guo said recent research on the prevalence of T2DM has shown gender-related differences, especially a reduced incidence of the disease in premenopausal women. Studies have shown a strong correlation between estrogen deficiency and metabolic dysfunction. Estrogen deficiency or impaired estrogen signaling is associated with insulin resistance and faulty regulation of metabolic homeostasis, which contributes to the development of T2DM and obesity in both human and animal models. But the exact contribution of the tissue-specific action of estrogen to metabolic changes and underlying mechanisms have not yet been elucidated.

Guo noted there is also a potential risk of breast cancer or stroke as a side effect of estrogen therapy, which is a significant roadblock to its use as a therapeutic agent. In their study, Guo and other researchers investigated the action of estrogen on glucose homeostasis in male and ovariectomized female control and liver-specific Foxo1 knockout mice.

"We wanted to understand the mechanism by which estrogen regulates gluconeogenesis by means of interaction with hepatic Foxo1," he explained. "Foxo1 has an important role in the regulation of glucose production through insulin signaling. It is an important component of insulin-signaling cascades regulating cellular growth, differentiation and metabolism."

The study results support the hypothesis that improvement of glucose homeostasis by estrogen is regulated by hepatic Foxo1-mediated gluconeogenesis rather than by promoting muscle glucose uptake. The results may also help explain why premenopausal women have a lower incidence of T2DM than age-equivalent men and suggest that targeting the estrogen receptor ERa can be a potential approach to modulate glucose metabolism and prevent diabetes. "The identification of tissue-specific actions of estrogen and direct targets of estrogen receptors will facilitate the development of novel selective ligands that prevent Type 2 diabetes, cardiovascular disease and obesity without promoting abnormal sex characteristics or breast cancer," Guo said.

Guo also noted that some foods, such as soybeans, contain a certain amount of phytoestrogens, which can function in a similar way to that of estrogen, regulating bodily glucose metabolism and insulin sensitivity. "This study provides some important insights into the molecular and physiological mechanism of metabolic diseases and provides a fundamental understanding that dietary intervention can play a crucial role in controlling obesity, diabetes and associated chronic diseases," he said.

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