Diabetes Targeted by New "Hormone Hybrids"

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An team of scientists may have achieved a major milestone in the treatment of diabetes and obesity. The researchers engineered a method to deliver hormones to specific tissues in the body, while keeping them away from others.

The team, led by Dr. Matthias Tschöp, from the Technical University of Munich and the Helmholtz Center, and Richard DiMarchi, a chemist at Indiana University, was able to engineer natural gut peptides to carry small steroids known to act at the cell nucleus. Their hope was to deliver the steroid only inside cells.

The researchers started with a gut hormone that is known to act on pancreas and brain cells to improve insulin secretion, blood glucose, and body weight. They engineered the hormone to reversibly bind estrogen, which is known to provide metabolic benefits at the same target cells. The results show that the team was able to "multiply" the metabolic benefits to mice, without the side effects that large doses of estrogen normally have on reproductive organs, such as an increased cancer risk. Likewise, there was no evident impact on the growth of estrogen-sensitive tumors.

The effect on pancreas and brain tissue in the mice were evident, however. This suggests the researchers have succeeded in the targeted delivery of steroids to specific cells. With more development, the technique could be used to more accurately treat diabetes and metabolic syndrome (high blood pressure, high cholesterol, high blood sugar, and obesity). A study based on the results of the team's experiments has been published in the journal Nature Medicine.

“Our novel GLP-1/estrogen molecules seem to outperform more traditional therapeutics in mouse models of obesity and type 2 diabetes” said Brian Finan, lead author of the study and researcher at the Helmholtz Center. “What we are even more excited about is the opportunity to use targeted steroid hormone for other diseases, where side effects had prevented therapeutic use in the past."

(Image courtesy the Technical University of Munich)

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