How fructose is transported into our cells could lead to treatments for cancer, obesity, and diabetes.
Adam Rifkin stashed this in Science!
To see what the real discovery is, you have to go to the linked abstract on nature.com.
The altered activity of the fructose transporter GLUT5, an isoform of the facilitated-diffusion glucose transporter family, has been linked to disorders such as type 2 diabetes and obesity.
So it's not that we've newly discovered GLUT5's purpose, it's that they found out it acts strangely in certain diseases.
GLUT5 is also overexpressed in certain tumour cells, and inhibitors are potential drugs for these conditions.
This is notable because fructose is almost exclusively metabolized by liver cells (assuming we're not talking only about liver cancer). So why would we see lots of GLUT5 anywhere other than the liver?
On the basis of a comparison of the inward-facing structures of GLUT5 and human GLUT1, a ubiquitous glucose transporter, we show that a single point mutation is enough to switch the substrate-binding preference of GLUT5 from fructose to glucose.
And here it is. Certain diseases can apparently re-task the fructose transporter GLUT5 to move glucose instead, which all the cells in the body can utilize. Also, the number of transporters is increased. This is just a mechanism to get more glucose into the cells faster, which makes sense when you see the diseases linked to this. Seems like a strange workaround to use a fructose transporter instead of more GLUT1, but hey, it's a mutation.
The bit about cancer inhibitors is promising. Cancer is repurposing GLUT5 so it can grow faster. Your body doesn't need fructose in any capacity, so if you completely block GLUT5 through your entire body, you can slow cancer growth without hurting normal cells.
My expertise is in pancreatic cancer, and the shunting of fructose into an adipogenesis pathway (fat-creation) as opposed to glucose-based energy generation, is an emerging disease-development mechanism in pancreatic cancer.
Our understanding is that this abnormally high amount of fructose->fat conversion, mediated by the endocrine AND exocrine components of pancreas, causes chronic pancreatitis. This chronic inflammatory environment is pro-tumorigenic, and may lead to the development of adenocarcinoma. Given our high consumption of fructose this could be a significant contributor to the rapid increase in pancreatic cancer over the past 40 years or so.
If we could block even a portion of fructose metabolism that is going on in our bodies we would be happier, healthier, skinnier, and most likely less prone to cancer.
Every time you eat a cheeseburger you have a single bout of acute pancreatitis, which literally destroys the pancreas. The next few days will involve the cleanup and repair back to a pristine pancreas. This happens all the time and it's OK. But, when it becomes a chronic condition then the inflammation never stops.
This results in scarring, desmoplasia, and lots of free-radicals, which induce mutations. Once you have a loss of function mutation in p53 (global tumor suppressor) and a gain of function mutation in RAS (a master regulator of proliferation & migration) then you are well on your way to pancreatic cancer. Specific mutations in these two genes are sufficient to explain 50-90% of all pancreatic cancers. More mutations eventually inevitably occur during this tumorigenic process.
The big mystery is why the B-cells (antibody producing white blood cells) in this inflamed pancreas begin to protect the emergent tumor. It has been demonstrated that the very immune cells in charge of identifying tumor cells suddenly start doing the opposite. They secrete cytokines and immunoregulatory factors that tell the immune system to back off: "everything looks fine here." Presumably the tumor is secreting something that tells these B-cells to become protumorigenic rather than antitumorigenic. It's a common theme in many cancers - immunoregulatory microenvironment.
The other big problem is all the scar tissue (desmoplasia) that is created during tumor development. All this extra stuff causes the blood vessels to collapse. This creates a low-oxygen environment that promotes further mutations and provides a strong selective pressure for the most aggressive mutations that further tumorigenesis.
What's more, it's very difficult to get chemotherapy administered IV to actually get inside the tumor because of these collapsed blood vessels.
The pancreas is just the perfect environment for inflammation-mediated tumorigenesis.