Drugs that treat diabetes may also be effective against some cancers. In todays Journal of Biology, researchers at the University of Dundee report the discovery of an unexpected link between diabetes and Peutz-Jeghers syndrome, a hereditary disease that increases the risk of suffering from cancer.
The Dundee team were looking for a protein that activates AMPK, an enzyme that reduces blood glucose levels and is a target for drugs commonly used in treating Type 2 diabetes.
They hoped that this protein would be a target for new anti-diabetes drugs, and their search ended with an enzyme called LKB1. Surprisingly, a lack of LKB1 is a known cause of Peutz-Jeghers syndrome, in which the risk of developing some cancers is 15 times higher than normal.
"It was totally unexpected," said Dario Alessi, one of the research team leaders. "LKB1 was thought of as a tumour suppressor gene, and AMPK was involved in diabetes. No one thought that there could be a link between the two."
Grahame Hardie, the second team leader, said: "The idea that LKB1 might switch on AMPK came from work I did on a related system in the simple single-cell organism brewers yeast. [...] The idea that LKB1 might be the key was a genuine Eureka moment, especially when I realised that Dario Alessi already worked on it and had all of the expertise necessary to test the idea."
Having identified the LKB1 enzyme in yeast, the Dundee team looked for its counterpart in rat liver extracts that could activate AMPK. They not only identified the rat version of LKB1, but also found two proteins that bind to LKB1 and enhance its activity. When the researchers removed LKB1 from the extract, they found that the extract could no longer activate AMPK, consistent with LKB1 being the activating enzyme.
LKB1 normally acts to prevent tumour growth. The way that it does this was unclear until now, but this research suggests that its tumour-preventing properties may be dependent on its ability to activate AMPK. This would make sense as active AMPK not only reduces blood glucose levels, but can also inhibit cell division and the production of molecules required for cell growth.
Patients with Type 2 diabetes commonly have high levels of glucose in their bloodstreams. Active AMPK reduces these by inducing muscles to take up glucose from the blood, and inhibiting glucose production. Some common anti-diabetes drugs target AMPK, increasing its activity. Intriguingly, the researchers found that one such drug, metformin, the active ingredient of the glucophage medicine, was ineffective in cells that contained no LKB1. Alessi said: "It is not yet clear whether metformin directly activates LKB1, our research didnt test this. It is one of the things to find out in the future." However, he believes that drugs which activate LKB1 could be more effective at treating diabetes than current therapies.
Although metformin would be ineffective against Peutz-Jeghers syndrome, as the tumours would not have any LKB1, virtually all other tumours retain their LKB1 activity. Alessi explains: "An exciting possibility is that metformin could be used for treating some forms of cancer. Metformin is the most widely used diabetes drug in the world. It will be interesting to see if people on metformin get less cancer - the data must be out there somewhere."
This press release is based on the following article:
Complexes between the LKB1 tumor suppressor, STRADa/b and MO25 a/b are upstream kinases in the AMP-activated protein kinase cascade.
Simon A Hawley, Jerome Boudeau, Jennifer L Reid, Kirsty J Mustard, Lina Udd, Tomi P Makela, Dario R Alessi and D Grahame Hardie.
Journal of Biology 2:28
Published 24th September 2003 16:00 GMT
Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences