Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Penn study shows how next-generation diabetic drugs could work more selectively

28.01.2005


Understanding molecular double action of tzds to reduce side effects



In an attempt to find a new generation of diabetic drugs that will minimize side effects, researchers at the University of Pennsylvania School of Medicine report a new understanding of how thiazolidinediones (TZDs), widely used diabetic medications, work in fat cells. With yearly sales exceeding billions of dollars, TZDs – such as rosiglitazone maleate (Avandia) and pioglitazone hydrochloride (Actos) – help to maintain diabetics’ blood-sugar levels.

In fat cells, TZDs turn on a small set of genes, which aren’t normally turned on, by targeting the receptor PPARã. To tease out how the medications work specifically, the investigators set out to determine the difference between the genes that are ordinarily turned on in fat cells and the genes that are turned on only when diabetics are given the TZDs.


A new study from the laboratory of Mitchell Lazar, MD, PhD, Director of the Institute for Diabetes, Obesity, and Metabolism at Penn, has found that PPARã can turn genes both on and off. "What regulates it, in this case, is the drug, which is acting as a switch to turn genes on," says Lazar. "This paper shows that we can separate the two different aspects of the drug’s action on fat cells." These findings appear in the January 28th online edition of Genes & Development and will appear in the February 15th print issue.

Knowing how to turn a gene off may permit researchers to develop drugs that would decrease TZD-related side effects such as weight gain and edema. Indeed, preclinical research is already underway to design drugs called SPPARMs, selective PPARã modulators, which would specifically target genes in fat cells that can turn off the molecular pathways that may lead to these serious side effects.

Working with mouse fat cells, Lazar’s study suggests that one way to get gene-selective actions would be to target this ability to turn off genes without affecting the ability to turn others on. "Since these are separate processes, one through one type of molecular action and one through another, our work shows that this is feasible," says Lazar

How would a SPPARM work? TZDs turn genes on and off by working with molecules called coactivators and corepressors. In addition to its beneficial role, TZDs turn fibroblasts into fat cells by enlisting more coactivators than normal, thus leading to weight gain. The goal is to design a SPPARM that will reduce interaction with corepressors, but increase interaction with coactivators, to separate anti-diabetic effects and weight gain.

"We should be optimistic about finding a new type of drug with the same fat-cell target as TZDs, but which is a selective regulator of gene expression in such a way that will increase the benefit-to-risk ratio of the diabetes treatment," says Lazar.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Studies and Analyses:

nachricht The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>