Using animal models, the researchers discovered that pancreatic islet cells transplanted into the liver fail not only because of immune rejection, but also because of overexposure to toxic fats that are synthesized by the surrounding liver cells and flood the pancreatic transplants. Their findings appear in the September issue of the journal Diabetes.
To date, a few hundred people have received transplants of complexes of pancreatic cells, called islets. The islets are implanted in the liver, where they at first make insulin, but over months or years their production often declines.
“By understanding how fat affects these cells, maybe we can improve islet transplant and make it last a bit longer,” said Dr. Roger Unger, professor of internal medicine at UT Southwestern and senior author of the study.
During islet transplantation, the pancreatic cell complexes are injected into a large vein that feeds into the liver, where they lodge. Cells within the islets, called beta cells, then produce insulin. The person receiving the transplant must take anti-rejection drugs.
Dr. Unger said that after two years, 87 percent of recipients must resume taking insulin, a problem that has led clinicians to investigate if the anti-rejection drugs are at fault, or if some other mechanism is at work.
In the current study, UT Southwestern researchers tested the hypothesis that fats in the liver might be killing the beta cells. The liver receives its blood supply directly from the digestive system, which provides a rich concentration of fats and sugars to the transplanted islet cells – conditions the cells would not be exposed to in their normal environment in the pancreas. The researchers also theorized that the insulin that each islet produced might stimulate fat production around itself, adding to the problem.
The researchers first injected rats with a drug that kills pancreatic beta cells in order to mimic human insulin-dependent, or juvenile, diabetes (type 1), a condition in which beta cells are unable to produce insulin. They then transplanted beta cells into the animals’ livers. Fat accumulations were found around islets four weeks after transplantation. Insulin levels declined, and the animals died at 15 weeks.
Another group of similar rats was then exposed to one of two conditions that reduce body fat – a restricted diet or administration of leptin, a hormone that decreases appetite and increases metabolism. In both cases, more beta cells survived. Rats that had received leptin also showed the highest survival rate of beta cells.
Because the differences among the groups of rats could be traced to the amount of fat, and no anti-rejection drugs had been given, the results validate their theory that fat was the culprit in killing the beta cells, Dr. Unger said.
These results also suggest that diet and weight control might enable transplanted beta cells in humans to survive longer or avoid destruction, he said.
“This seems very easy to prevent, but it’s not being targeted by researchers,” he said.
Dr. Unger said the study could also serve as a model for death of beta cells in non-insulin-dependent, or adult-onset, diabetes (type 2), a condition that is associated largely with obesity. His group is now working with other researchers at UT Southwestern to determine if excess fat is killing cells in obese humans.
Aline McKenzie | EurekAlert!
Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung
Scientists reveal source of human heartbeat in 3-D
07.08.2017 | University of Manchester
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).
The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
16.08.2017 | Physics and Astronomy
16.08.2017 | Materials Sciences
16.08.2017 | Interdisciplinary Research