Featured Research

from universities, journals, and other organizations

Turbo-charged gut hormones: Doubling down against diabetes

Date:
November 13, 2012
Source:
Technische Universitaet Muenchen
Summary:
Researchers may have overcome one of the major challenges drug makers have struggled with for years: Delivering powerful nuclear hormones to specific tissues, while keeping them away from others.

A collaboration between scientists in Munich, Germany and Bloomington, USA may have overcome one of the major challenges drug makers have struggled with for years: Delivering powerful nuclear hormones to specific tissues, while keeping them away from others.

The teams led by physician Matthias Tschöp (Helmholtz Zentrum München, and Technische Universität München) and chemist Richard DiMarchi (Indiana University) used natural gut peptides targeting cell membrane receptors and engineered them to carry small steroids known to act at the cell nucleus. DiMarchi and Tschöp hoped that such "turbo-charged" hormone hybrids would only deliver their steroid inside cells, where their specific peptide receptor was expressed at the surface.

Both teams had been working together for years to discover new ways to treat obesity and diabetes. They therefore started out with the gut hormone glucagon-like peptide-1, which is known to act at pancreas and brain cells to improve insulin secretion, blood glucose, and body weight. They engineered these peptides to reversibly bind the female sex steroid, estrogen, which is also known to confer powerful metabolic benefits at some of the same target cells. In the past, pharmacologists had been unable to utilize such benefits as high doses of systemic estrogen can also powerfully affect reproductive organs and increase cancer risk.

Using their GLP-1/estrogen-conjugates however, DiMarchi and Tschöp found that they were able to multiply metabolic benefits in mice, without apparent side effects on estrogen-sensitive reproductive organs such as the uterus. They also found no impact of their "turbo-charged" gut peptides on growth of estrogen-sensitive tumors. Genetic studies at the same time however uncovered clear estrogen effects in pancreas and brain tissue of mice treated with the new combination drug candidate, indicating that the collaborating teams had indeed succeeded with targeted delivery of steroids.

"Our novel GLP-1/estrogen molecules seem to outperform more traditional therapeutics in mouse models of obesity and type 2 diabetes" says Brian Finan, scientist at the Helmholtz Zentrum München and first author of the study published online in the journal Nature Medicine. "What we are even more excited about" he adds "is the opportunity to use targeted steroid hormone for other diseases, where side effects had prevented therapeutic use in the past. "There is still a lot we don't know about the mechanistic details," cautions Matthias Tschöp, director of the Helmholtz Institute for Diabetes and Obesity "but if they proof safe enough for clinical use, these molecules could offer transformative potential."


Story Source:

The above story is based on materials provided by Technische Universitaet Muenchen. Note: Materials may be edited for content and length.


Journal Reference:

  1. Brian Finan, Bin Yang, Nickki Ottaway, Kerstin Stemmer, Timo D Müller, Chun-Xia Yi, Kirk Habegger, Sonja C Schriever, Cristina García-Cáceres, Dhiraj G Kabra, Jazzminn Hembree, Jenna Holland, Christine Raver, Randy J Seeley, Wolfgang Hans, Martin Irmler, Johannes Beckers, Martin Hrabě de Angelis, Joseph P Tiano, Franck Mauvais-Jarvis, Diego Perez-Tilve, Paul Pfluger, Lianshan Zhang, Vasily Gelfanov, Richard D DiMarchi, Matthias H Tschöp. Targeted estrogen delivery reverses the metabolic syndrome. Nature Medicine, 2012; DOI: 10.1038/nm.3009

Cite This Page:

Technische Universitaet Muenchen. "Turbo-charged gut hormones: Doubling down against diabetes." ScienceDaily. ScienceDaily, 13 November 2012. <www.sciencedaily.com/releases/2012/11/121113122042.htm>.
Technische Universitaet Muenchen. (2012, November 13). Turbo-charged gut hormones: Doubling down against diabetes. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2012/11/121113122042.htm
Technische Universitaet Muenchen. "Turbo-charged gut hormones: Doubling down against diabetes." ScienceDaily. www.sciencedaily.com/releases/2012/11/121113122042.htm (accessed July 24, 2014).

Share This




More Health & Medicine News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Newsy (July 23, 2014) — An 8-year-old boy helped his younger brother, who has a rare genetic condition that's confined him to a wheelchair, finish a triathlon. Video provided by Newsy
Powered by NewsLook.com
Thousands Who Can't Afford Medical Care Flock to Free US Clinic

Thousands Who Can't Afford Medical Care Flock to Free US Clinic

AFP (July 23, 2014) — America may be the world’s richest country, but in terms of healthcare, the World Health Organisation ranks it 37th. Thousands turned out for a free clinic run by "Remote Area Medical" with a visit from the Governor of Virginia. Duration: 2:40 Video provided by AFP
Powered by NewsLook.com
Stone Fruit Listeria Scare Causes Sweeping Recall

Stone Fruit Listeria Scare Causes Sweeping Recall

Newsy (July 22, 2014) — The Wawona Packing Company has issued a voluntary recall on the stone fruit it distributes due to a possible Listeria outbreak. Video provided by Newsy
Powered by NewsLook.com
Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Newsy (July 22, 2014) — The 83 new genetic markers could open dozens of new avenues for schizophrenia treatment research. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins