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

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

Study reveals key molecular link in major cell growth pathway

October 19, 2017
A team of scientists led by Whitehead Institute has uncovered a surprising molecular link that connects how cells regulate growth with how they sense and make available the nutrients required for growth. Their work, which ...

Inflammation trains the skin to heal faster

October 18, 2017
Scars may fade, but the skin remembers. New research from The Rockefeller University reveals that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, ...

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.