Fat Development Leads to Pancreatic Cell Transplant Failure

Researchers have found that the failure of pancreatic cell transplants to provide a lasting source of insulin is due in part to the toxic effect of high levels of fats that form in the vicinity of the transplant.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) were seeking factors other than immune rejection that could explain the poor results obtained by pancreatic cell transplant therapy.

The investigators transplanted beta cells into the livers of rats that had been chemically treated to mimic human insulin-dependent, or juvenile diabetes (type 1), a condition in which pancreatic beta cells are unable to produce insulin. Some of the animals were also treated to reduce production of fats, either by restricting diet or by receiving leptin, a hormone that decreases appetite and increases metabolism.

Results published in the September 2007 issue of the journal Diabetes revealed that after an initial increase in insulin production the untreated rats developed fat accumulations within four weeks after transplantation. Insulin levels declined, and the animals died at 15 weeks. In the two treated groups, more beta cells survived with rats that had received leptin, showing the highest survival rate of beta cells.

"By understanding how fat affects these cells, maybe we can improve islet transplant and make it last a bit longer,” said senior author Dr. Roger Unger, professor of internal medicine at the University of Texas Southwestern Medical Center. "This seems very easy to prevent, but it's not being targeted by researchers.”


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University of Texas Southwestern Medical Center