(Press-News.org) An enzyme called 12-LO promotes the obesity-induced oxidative stress in the pancreatic cells that leads to pre-diabetes, and diabetes. 12-LO's enzymatic action is the last step in the production of certain small molecules that harm the cell, according to a team from Indiana University School of Medicine, Indianapolis. The findings will enable the development of drugs that can interfere with this enzyme, preventing or even reversing diabetes. The research is published ahead of print in the journal Molecular and Cellular Biology.
Nearly 40 percent of Americans—more than 120 million people—have diabetes or pre-diabetes. Diabetes results when the pancreas fails to produce sufficient insulin to remove sugar from the blood.
"We surmised that when individuals eat high fat foods and become overweight, the beta cells of their pancreases fail to produce sufficient insulin," says principal investigator Raghavendra Mirmira. In earlier studies, these researchers and their collaborators at Eastern Virginia Medical School showed that 12-LO (which stands for 12-lipoxygenase) is present in these cells only in people who become overweight.
The harmful small molecules resulting from 12-LO's enzymatic action are known as HETEs, short for hydroxyeicosatetraenoic acid. HETEs harm the mitochondria, which then fail to produce sufficient energy to enable the pancreatic cells to manufacture the necessary quantities of insulin.
For the study, the investigators genetically engineered mice that lacked the gene for 12-LO exclusively in their pancreas cells. Mice were either fed a low-fat or high-fat diet.
Both the control mice and the knockout mice on the high fat diet developed obesity and insulin resistance. The investigators also examined the pancreatic beta cells of both knockout and control mice, using both microscopic studies and molecular analysis. Those from the knockout mice were intact and healthy, while those from the control mice showed oxidative damage, demonstrating that 12-LO and the resulting HETEs caused the beta cell failure.
Mirmira notes that fatty diet used in the study was the Western Diet, which comprises mostly saturated—"bad"—fats. Based partly on a recent study of related metabolic pathways, he says that the unsaturated and mono-unsaturated fats—which comprise most fats in the healthy, relatively high fat Mediterranean diet—are unlikely to have the same effects.
"Our research is the first to show that 12-LO in the beta cell is the culprit in the development of pre-diabetes, following high fat diets," says Mirmira. "Our work also lends important credence to the notion that the beta cell is the primary defective cell in virtually all forms of diabetes and pre-diabetes."
INFORMATION:
The manuscript can be found online at http://bit.ly/asmtip0814b. The final version of the article is scheduled for the October 2014 issue of Molecular and Cellular Biology.
Molecular and Cellular Biology is a publication of the American Society for Microbiology (ASM). The ASM is the largest single life science society, composed of over 39,000 scientists and health professionals. Its mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.
Single enzyme is necessary for development of diabetes
2014-08-14
ELSE PRESS RELEASES FROM THIS DATE:
Parasitic worms sniff out their victims as 'cruisers' or 'ambushers'
2014-08-14
It has been speculated that soil-dwelling parasitic worms use their sense of smell to find suitable hosts for infection. Research published on August 14th in PLOS Pathogens comparing odor-driven behaviors in different roundworm species reveals that olfactory preferences reflect host specificity rather than species relatedness, suggesting that olfaction indeed plays an important role in host location.
To study worm olfaction, Elissa Hallem, from the University of California Los Angeles, USA, and colleagues examined the host-seeking strategies and sensory behaviors of different ...
Drugs that flush out HIV may impair killer T cells, possibly hindering HIV eradication
2014-08-14
Histone deacetylase (HDAC) inhibitors have shown promise in "flushing out" HIV from latently infected cells, potentially exposing the reservoirs available for elimination by cytotoxic T lymphocytes (CTL), also called killer T cells. However, findings published on August 14th in PLOS Pathogens now suggest that treatment with HDAC inhibitors might suppress CTL activity and therefore compromise the "kill" part of a two-pronged "flush-and-kill" HIV eradication strategy.
At least three different HDAC inhibitors, romidepsin, panobinostat, and SAHA, are under investigation as ...
Plants may use newly discovered language to communicate, Virginia Tech scientist discovers
2014-08-14
VIDEO:
This time-lapse video shows how the parasitic plant dodder attacks tomatoes. But beyond stealing nutrients from the host plants, a Virginia Tech researcher has discovered that the two plants also...
Click here for more information.
A Virginia Tech scientist has discovered a potentially new form of plant communication, one that allows them to share an extraordinary amount of genetic information with one another.
The finding by Jim Westwood, a professor of plant pathology, ...
Human contribution to glacier mass loss on the increase
2014-08-14
This news release is available in German.
The ongoing global glacier retreat causes rising sea-levels, changing seasonal water availability and increasing geo-hazards. While melting glaciers have become emblematic of anthropogenic climate change, glacier extent responds very slowly to climate changes. "Typically, it takes glaciers decades or centuries to adjust to climate changes," says climate researcher Ben Marzeion from the Institute of Meteorology and Geophysics of the University of Innsbruck. The global retreat of glaciers observed today started around the middle ...
Seven tiny grains captured by Stardust likely visitors from interstellar space
2014-08-14
Since 2006, when NASA's Stardust spacecraft delivered its aerogel and aluminum foil dust collectors to Earth, a team of scientists has combed through the collectors in search of rare, microscopic particles of interstellar dust.
The team now reports that they have found seven dust motes that probably came from outside our solar system, perhaps created in a supernova explosion millions of years ago and altered by eons of exposure to the extremes of space. They would be the first confirmed samples of contemporary interstellar dust.
"They are very precious particles," ...
Memories of errors foster faster learning
2014-08-14
Using a deceptively simple set of experiments, researchers at Johns Hopkins have learned why people learn an identical or similar task faster the second, third and subsequent time around. The reason: They are aided not only by memories of how to perform the task, but also by memories of the errors made the first time.
"In learning a new motor task, there appear to be two processes happening at once," says Reza Shadmehr, Ph.D., a professor in the Department of Biomedical Engineering at the Johns Hopkins University School of Medicine. "One is the learning of the motor ...
Harnessing the power of bacteria's sophisticated immune system
2014-08-14
Bacteria's ability to destroy viruses has long puzzled scientists, but researchers at the Johns Hopkins Bloomberg School of Public Health say they now have a clear picture of the bacterial immune system and say its unique shape is likely why bacteria can so quickly recognize and destroy their assailants.
The researchers drew what they say is the first-ever picture of the molecular machinery, known as Cascade, which stands guard inside bacterial cells. To their surprise, they found it contains a two-strand, unencumbered structure that resembles a ladder, freeing it to ...
Message to parents: Babies don't 'start from scratch'
2014-08-14
There's now overwhelming evidence that a child's future health is influenced by more than just their parents' genetic material, and that children born of unhealthy parents will already be pre-programmed for greater risk of poor health, according to University of Adelaide researchers.
In a feature paper called "Parenting from before conception" published in today's issue of the top international journal Science, researchers at the University's Robinson Research Institute say environmental factors prior to conception have more influence on the child's future than previously ...
A self-organizing thousand-robot swarm
2014-08-14
Cambridge, Mass. – August 14, 2014 – The first thousand-robot flash mob has assembled at Harvard University.
"Form a sea star shape," directs a computer scientist, sending the command to 1,024 little bots simultaneously via an infrared light. The robots begin to blink at one another and then gradually arrange themselves into a five-pointed star. "Now form the letter K."
The 'K' stands for Kilobots, the name given to these extremely simple robots, each just a few centimeters across, standing on three pin-like legs. Instead of one highly-complex robot, a "kilo" of robots ...
Molecular engineers record an electron's quantum behavior
2014-08-14
A team of researchers led by the University of Chicago has developed a technique to record the quantum mechanical behavior of an individual electron contained within a nanoscale defect in diamond. Their technique uses ultrafast pulses of laser light both to control the defect's entire quantum state and observe how that single electron state changes over time. The work appears in this week's online Science Express and will be published in print later this month in Science.
This research contributes to the emerging science of quantum information processing, which demands ...