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
One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center
The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.
New Manufacturing Technologies for New Products
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
22.06.2017 | Life Sciences
22.06.2017 | Materials Sciences
22.06.2017 | Materials Sciences