MicroRNA derails protein that blocks insulin production

September 20, 2012 by Marcia Goodrich
MicroRNA derails protein that blocks insulin production
Diabetes, a disease affecting nearly 26 million Americans, results when insulin fails to ferry glucose into cells, causing sugar to accumulate in the blood. Xiaoqing Tang has shed light on the insulin production process.

(Medical Xpress)—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, and stroke. Diabetes results when the does not produce or release enough insulin into the or when cells fail to respond to the hormone.

The in question is a microRNA molecule called miR-30d, which is the same in mice and people. MicroRNA, or miRNA, attaches to long 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 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 from 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.

"What we found with miR-30d is that it can increase cells' ability to make insulin by activating MafA," Tang said. "We've also shown that the tumor necrosis factor–triggered MAP4K4 is a direct target of miR-30d. Based on our data, we think miR-30d probably plays multiple roles, both in enhancing and in protecting cells from the inflammatory effects of ."

Their latest research was published online Sept. 7 in The Journal of Biological Chemistry. The article, "MicroRNA-30d Induces Insulin Transcription Factor MafA and Insulin Production by Targeting Mitogen-Activated Protein 4 Kinase 4 in Pancreatic Beta Cells," was authored by Tang, Xiaomin Zhao and Ramkumar Mohan of Michigan Tech; and Sabire Ozcan of the University of Kentucky.

Tang is now studying transgenic mice that generate extra amounts of miR-30d. "We want to induce diabetes and see if the process slows down in the transgenic mice," she said. "If that happened, it would be great."

The study is in its early stages, but preliminary results are intriguing. The transgenic mice are smaller and leaner than wild mice. Yet they don't seem to have extra insulin in their blood.

"We still don't understand why insulin is low in the blood of the transgenic mice." she said. "It may mean that insulin gets into cells from the blood very quickly. Or, the beta cells in the pancreas may sense that they don't need to produce much insulin. Or maybe it's another process all together. A mouse is much more complicated than a cell line."

Explore further: Scientists use uterine stem cells to treat diabetes

Related Stories

Scientists use uterine stem cells to treat diabetes

September 14, 2011
Controlling diabetes may someday involve mining stem cells from the lining of the uterus, Yale School of Medicine researchers report in a new study published in the journal Molecular Therapy. The team treated diabetes in ...

Researchers identify key role of microRNAs in melanoma metastasis

July 11, 2011
Researchers at the NYU Cancer Institute, an NCI-designated cancer center at NYU Langone Medical Center, identified for the first time the key role specific microRNAs (miRNAs) play in melanoma metastasis to simultaneously ...

Stem cells can beat back diabetes: UBC research

June 27, 2012
University of British Columbia scientists have successfully reversed diabetes in mice using stem cells, paving the way for a breakthrough treatment for a disease that affects nearly one in four Canadians.

Researchers discover protein that may represent new target for treating type 1 diabetes

January 4, 2012
Researchers at Wake Forest Baptist Medical Center's Institute for Regenerative Medicine and colleagues have discovered a new protein that may play a critical role in how the human body regulates blood sugar levels. Reporting ...

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.