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
Usher syndrome: Gene therapy restores hearing and balance
25.09.2017 | Institut Pasteur
MRI contrast agent locates and distinguishes aggressive from slow-growing breast cancer
25.09.2017 | Case Western Reserve University
Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.
Graphene is up to the job
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
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
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...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
26.09.2017 | Information Technology
26.09.2017 | Physics and Astronomy
26.09.2017 | Life Sciences