New research strengthens the idea that estrogen therapy could help to prevent type 2 diabetes following menopause, after it identified the mechanisms by which the hormone helps to control blood sugar levels.

In a study of postmenopausal mice and human cells, researchers found that estrogen targets specific cells in the pancreas and the gut to increase tolerance to glucose.

This is associated with a lower risk of type 2 diabetes.

Study leader Jacques Philippe, who is a diabetes specialist currently working at the University of Geneva's Faculty of Medicine in Switzerland, and colleagues recently reported their results in the journal JCI Insight.

It is estimated that around 30.3 million people in the United States—or around 9.4% of the population—are living with diabetes, which is a condition that causes blood glucose levels to become too high.

Type 2 diabetes—which arises when the body struggles to effectively use insulin, the hormone that regulates blood sugar—accounts for approximately 90%–95% of all diabetes cases.

Previous research has suggested that after menopause, women may face a greater risk of type 2 diabetes. This has been attributed to hormonal changes, such as a reduction in estrogen levels.

Following on from such studies, scientists have investigated whether or not estrogen replacement therapy could help to prevent type 2 diabetes among postmenopausal women, and many studies have produced positive results.

That being said, the exact mechanisms by which estrogen may protect against type 2 diabetes have been unclear—until now.

Estrogen targets pancreatic and gut cells

For their study, Philippe and colleagues administered estrogen to postmenopausal mice.

While previous studies have primarily focused on how estrogen affects the insulin-producing cells of the pancreas, this latest study also looked at how the hormone impacts cells that produce glucagon, which is a hormone that increases blood glucose.

"Indeed," says Philippe, "if the pancreas secretes insulin, it also secretes glucagon, a hormone with the opposite effect: insulin captures sugar, while glucagon releases it. Diabetes is therefore due to an imbalance between these two hormones controlling the sugar level in the blood."

The new study revealed that the alpha cells of the pancreas, or cells that secrete glucagon, are highly sensitive to estrogen; the hormone causes them to release less glucagon, but more of a hormone called GLP1.

And, notably, GLP1 is also released by the intestine after eating; it encourages inulin secretion, blocks glucagon secretion, and increases feelings of fullness.

"Indeed, the gut harbors cells called the L cells that are very similar to pancreatic alpha cells and whose main function is precisely to produce GLP1," explains first study author Sandra Handgraaf, also of the Faculty of Medicine at the University of Geneva.

"We also observed a strong increase in the production of GLP1 in the gut cells," she explains, "thus proving the crucial role of the intestine in the control of carbohydrate balance and the influence of estrogens on the entire metabolisms at stake."

The researchers were able to confirm their results in human cell lines.

Estrogen therapy may be beneficial

Hormone replacement therapy has been associated with a number of health risks for women who are postmenopausal, such as a greater risk of cardiovascular disease.

"[...] if hormonal treatment is taken more than 10 years after menopause, the cardiovascular risk is effectively increased," notes Philippe.

However, he adds that undergoing estrogen replacement therapy for only a few years shortly after menopause does not appear to raise cardiovascular risk. It could also help to reduce the risk of type 2 diabetes.

"In the context of diabetes, an estrogenic treatment allows to avoid, in all cases, the explosion of female diabetes cases. These treatments, well-administered, can really add value for women's health."

—Jacques Philippe