Mouse model developed at UT Southwestern mimics hyperglycemia, aids in diabetes research

"This model allows us to get a transcriptional signature, a fingerprint, of how beta cells fend off the pharmaceutical stimulus we provide to prompt cell death," Dr. Scherer said. "In other words, it provides a way to identify the most critical factors that protect against beta cell death and to potentially find ways to increase these factors in people with type 1 diabetes."

The key, Dr. Scherer said, is that the process researchers use to kill beta cells is very targeted.

"It creates very little inflammation, so we can eliminate specific cells with minimal collateral damage," he said. "The other nice aspect is that we can do it in a very dose-dependent way, so we can ablate, or kill, just a few cells, or we can ablate almost all of them."

Dr. Scherer said this model lends itself to studying conditions of temporary hyperglycemia such as gestational diabetes, a condition in which pregnant women who have never had diabetes develop hyperglycemia. Gestational diabetes usually disappears after pregnancy, but it is not clear whether these transient bouts of elevated glucose can cause permanent damage in the vasculature that persists even after normal glucose levels have been restored.

Dr. Zhao Wang, a postdoctoral researcher at UT Southwestern and lead author of the study, said the strength of the PANIC-ATTAC mouse as a research tool lies partly in the ability to test how specific pharmaceuticals impact beta-cell regeneration.

"We can test which drugs can more rapidly repair the damage," Dr. Wang said. "We can also test which drugs are protective. That's probably more important physiologically because it allows us to screen for interventions that could protect beta cells during the early stages of diabetes to slow down and prevent the onset of hyperglycemia."

Other UT Southwestern researchers involved in the study were Dr. Laurent Gautron, postdoctoral researcher; Dr. Todd Schraw, former postdoctoral researcher; and Dr. Joel Elmquist, professor of internal medicine. Researchers from the Albert Einstein College of Medicine and Merck Research Laboratories also participated.

The work was supported by the Juvenile Diabetes Research Foundation, the National Institutes of Health, and the American Heart Association.

Visit http://www.utsouthwestern.org/endocrinology to learn more about UT Southwestern's clinical services in endocrinology.

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Dr. Philipp Scherer -- http://www.utsouthwestern.edu/findfac/professional/0,2356,92752,00.html

Dr. Joel Elmquist -- http://www.utsouthwestern.edu/findfac/professional/0,2356,80436,00.html