Work by Michigan Technological University biologist Xiaoqing Tang is yielding new insights into how a tiny snippet of genetic material can promote healthy insulin production in mice.
Her work may eventually lead to new therapies for the treatment of diabetes, a disease that affects nearly 26 million Americans and causes myriad health problems, including heart disease, kidney failure and stroke. Diabetes results when the pancreas does not produce or release enough insulin into the blood stream or when cells fail to respond to the hormone.
The genetic material in question is a microRNA molecule called miR-30d, which is the same in mice and people. MicroRNA, or miRNA, attaches to long RNA molecules and prevents them from making proteins.
Proteins are the building blocks of life, but they can also cause serious problems; think of the plaques that develop in the brains of Alzheimer's patients.
One such protein is a tumor necrosis factor, which is involved in cell death and can trigger the production of another problematic protein, called MAP4K4, which blocks the formation of insulin when cells are under adverse conditions. MAP4K4 throws a wrench into the works by interfering with production of an important protein named MafA that binds to DNA and is an essential part of the insulin-making pathway.
In a series of experiments, Tang and her research team showed how miR-30d can counteract the tumor necrosis factor-triggered production of MAP4K4 and help the pancreas make more insulin.
First, they compared pancreas cells from diabetic mice with those of wild mice and found that the diabetic cells have much less miR-30d.
Second, using genes they created in their lab, they made cells that produce extra amounts of miR-30d. Those cells doubled the amount of the good protein MafA and generated much more insulin, showing that miR-30d works at least in part by activating MafA in the pancreas.
Finally, they added the tumor necrosis factor to those cells with the extra miR-30d. Unlike regular cells, which had MafA production blocked by the tumor necrosis factor, the super cells managed to keep on producing MafA, though not as much as before.