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Estrogen Treatment Helps To Prevent Type 2 Diabetes

Apr 21, 2018

New research shows how estrogen treatment helps to control blood sugar levels after menopause.

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, which is associated with a lower risk for type 2 diabetes.


Lead researcher 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.

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 up 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. While prior studies have 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.

When 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.

This new study showed us 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 GLP-1, which effects carbohydrate metabolism.

We also know that GLP-1 is also released by the intestine after eating; it encourages insulin secretion, blocks glucagon secretion, and increases feelings of fullness. The gut also produces GLP-1 via the L cells that are similar to the pancreatic alpha cells and its main function is to produce GLP-1. It is already known that GLP-1 provides a crucial role of the intestine in the control of carbohydrate balance and the influence of estrogens on the entire metabolism function.

Estrogen influences metabolism, acting both on pancreatic cells producing GLP1 and on so-called L cells the gut harbors, whose main function is also to produce GLP1.  Diabetes is therefore due to an imbalance between these two hormones, insulin and glucagon.

Estrogen therapy may be beneficial, but it also has been associated with a number of health risks for women who are postmenopausal, such as a greater risk of cardiovascular disease.

Dr. Philippe added that, “if hormonal treatment is taken more than 10 years after menopause, the cardiovascular risk is effectively increased.”  He also added 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.

From epidemiological data, we see an explosion of type 2 diabetes cases for women after menopause. We have seen the surprisingly protective role of estrogens, highlighted by the fact that a woman undergoing hormone replacement therapy has up to 35 percent less risk of developing type 2 diabetes than a woman without treatment. By elucidating how estrogen affects two of the hormones involved in glucose homeostasis, glucagon and GLP1, researchers at the University of Geneva (UNIGE), Switzerland, and at the Geneva University Hospitals (HUG) proved the value of estrogen supplementation from the onset of menopause.

Diabetes experts know that pre-menopausal women are less likely than men to develop type 2 diabetes. However, after menopause, the trend reverses very clearly, highlighting the protective role of women’s sexual hormones and especially estrogens. But what is their specific effect on metabolism? This question was answered by the team led by Jacques Philippe.

The study showed the sensitivity to estrogen on the pancreatic alpha cells, which then secrete less hyperglycemic glucagon, but more GLP1. These results confirm that this hormone stimulates the secretion of insulin, inhibits the secretion of glucagon and induces the feeling of satiety. The lack of GLP1 is therefore an essential and little-understood marker of the onset of diabetes. The role played by GLP1 represents a major explanation of the protection of women regarding diabetes onset before menopause.

Estrogen administration to post-menopausal female mice led the scientists to identify an increased tolerance to glucose, which is correlated to a lower risk of diabetes. However, if the effect on insulin was expected, the effect on glucagon—and especially on GLP1, an intestinal and pancreatic hormone that increases insulin production—was much less.

Practice Pearls:

  • The role GLP-1 plays is essential and little understood.
  • Estrogen therapy could help to prevent type 2 diabetes following menopause.
  • Estrogen targets specific cells in the pancreas and the gut to increase tolerance to glucose and lower the risk of type 2 diabetes.


JCI Insight, DOI: 10.1172/jci.insight.98569