"Estrogen is thought to have an important anti-diabetic effect. Women rarely contract the disease before they reach the menopause when their estrogen levels decrease dramatically," says Albert Salehi who heads the research group at Lund University Diabetes Centre in Malmö that made the discovery.
Suspected a third receptor
"We came across GPR30, the third, lesser known estrogen receptor, when we observed that the pharmacological blocking of traditional estrogen receptors did not have a significant effect on the capacity of estrogen to release insulin. The effect of estrogen on insulin secretion was not affected even in cases where these receptors were genetically knocked out. We began to suspect that insulin cells contain a third receptor," says Albert Salehi who has worked with estrogen and diabetes for several years.
Twofold effect
Insulin deficiency is generally considered to be the cause of type 2 diabetes. A substance able to increase the capacity of insulin cells to release insulin would counteract the disease. "We developed our theory and showed through animal experiments that the G-1 substance, which stimulates the GPR30 receptor but not the other two receptors, has a twofold effect. The release of insulin is stimulated when blood glucose rises and the secretion of glucagon, which raises blood glucose levels, is inhibited", explains Albert Salehi.
The group arrived at similar results during preliminary experiments using human insulin cells.
Developing a more potent substance
The G-1 substance is not as effective as estrogen, but experiments show that the principle works. The next step is to further develop new substances that are more potent than G-1. "In order to avoid side-effects, it is important that the substance only stimulates the GPR30 receptor. Such a substance could potentially become an effective drug for women with type 2 diabetes," Albert Salehi observes.
Counteracts inflammation
In the lab, the group has also shown that the protective effect of estrogen is due to the fact that the hormone forcibly counteracts the low intensity inflammation that in the long run kills off insulin cells in persons with type 2 diabetes. "We have seen that cell survival rates increase by several hundred percent when we use estrogen to suppress inflammation. The same effect is achieved by stimulating the GRP30 receptor," says Albert Salehi.
Contraceptive pills and weight gain
Finally, it is worth noting that weight gain is a common side-effect in healthy women who use contraceptive pills that contain estrogen. The reason for this weight gain is increased insulin release which, in turn, leads to increased hunger and appetite. "If it’s possible to stimulate the GPR30 receptor in an insulin cell without affecting the other two receptors, it can also be suppressed. It should then be possible to decrease undesirable weight gain resulting from the use of contraceptive pills," says Albert Salehi.
These data are published in the Molecular and Cellular Endocrinology journal.
Activation of G protein-coupled receptor 30 modulates hormone secretion and counteracts cytokine-induced apoptosis in pancreatic islets of female mice
http://www.sciencedirect.com/science/journal/03037207
For more information, please contact: Albert Salehi, +46 40 39 11 62, mobile +46 704 88 29 78
S_Albert [dot] Salehi [at] med [dot] lu [dot] se