Solution to insulin puzzle on track
Researchers have discovered a molecular "train carriage" that plays a key role in transporting glucose into cells, a finding that may help with developing type 2 diabetes treatments.
Scientists know that insulin triggers glucose transporter proteins to move from inside fat and muscle cells to the surface, where they can pump glucose into the cell.
They also know that in people with type 2 diabetes, only 10% of the cell's glucose transporters migrate to the cell membrane after a meal - compared to 80% in healthy people.
The exact molecular machinery involved in this process has long eluded scientists.
Yip and colleagues took a closer look at the link between insulin and a protein, called Myo1c, that had previously been linked to glucose uptake.
They found that Myo1c binds to glucose transporters, causing cells to take up glucose. When Myo1c is removed, the cells are unable to absorb glucose.
Using a high resolution microscope Yip and colleagues found that Myo1c acts like a molecular "train", carrying the glucose transporter proteins to the cell surface, along 'tracks' made of another protein called actin.
"In real time we saw that Myo1c moves with the glucose transporter to the cell surface," says Yip.
Importantly, the researchers found that insulin communicates with Myo1C via messenger chemicals and when these are blocked, the cells do not absorb glucose.
Yip believes people with type 2 diabetes have a communication breakdown between insulin and Myo1c.
If further research shows this communication breakdown does occurs, Yip says researchers may one day be able to find drugs that reinstate it.
Professor Mark Febbraio of the Baker IDI Heart and Diabetes Institute says existing drugs to treat insulin resistance are having limited success.
He says Yip's hypothesis could be proven, but it's important to be cautious and not over-optimistic.
Febbraio says 90% of Type-2 diabetes is linked to obesity, which itself causes insulin resistance.
"If you take a patient with insulin resistance and put them on a lifestyle intervention where they lose weight either by diet or exercise or both, in around 80-90% of cases the insulin resistance will go away," he says.
Febbraio himself is involved in developing an anti-obesity drug that will also combat insulin resistance.
Regardless of whether Yip and colleagues have found a new target for insulin resistance drugs, Febbraio says the new findings are important because so little is understood about how glucose transporters are transported to the cell surface.
"This research adds another piece in the jigsaw puzzle."