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
Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research