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, 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.
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 insulin production and in protecting cells from the inflammatory effects of tumor necrosis factor."
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."
Journal reference: Journal of Biological Chemistry
Provided by Michigan Technological University
- Insulin-releasing switch discovered Mar 15, 2011 | not rated yet | 0
- Scientists use uterine stem cells to treat diabetes Sep 14, 2011 | not rated yet | 0
- Researchers identify key role of microRNAs in melanoma metastasis Jul 11, 2011 | not rated yet | 0
- Researchers discover mechanism of insulin production that can lead to better treatment for diabetes Nov 12, 2009 | not rated yet | 0
- Stem cells can beat back diabetes: UBC research Jun 27, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research May 23, 2013 | 5 / 5 (1) | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research May 23, 2013 | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research May 23, 2013 | 3 / 5 (1) | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research May 23, 2013 | 5 / 5 (3) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research May 23, 2013 | 5 / 5 (2) | 0
(HealthDay)—Animals make great companions for senior citizens, but elderly people who always drive with a pet in the car are far more likely to crash than those who never drive with a pet, researchers have ...
3 hours ago | not rated yet | 0
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
11 hours ago | 5 / 5 (2) | 5
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
11 hours ago | not rated yet | 1
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...
11 hours ago | not rated yet | 0
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
11 hours ago | not rated yet | 0