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Islet & Pancreas Transplant Archives
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Fat: Pronounced Guilty in Death of Transplanted Beta Cells

Linda von Wartburg
14 September 2007
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When islet cells are transplanted into a person, they don't go into their usual home in the pancreas. Instead, they're injected into the portal vein, the large vein that feeds the liver with rich fats and sugars from the digestive system.

After the islet cells come to rest in the liver, their beta cells spring into action and begin making insulin. As time passes, unfortunately, less and less insulin is forthcoming.

Eighty-seven percent of human transplant recipients have to start taking insulin again a mere two years after the procedure. Something is knocking the beta cells out of commission, and that something, according to a recent study, is fat.

To reach their conclusion, the study authors first created a little herd of type 1 rats by killing off the rats' beta cells. Then they transplanted beta cells into the rats' livers without using anti-rejection drugs. Four weeks later, fat had accumulated around the islets. Insulin levels began to drop, and the rats died at fifteen weeks.

To test whether fat was the guilty party in the beta cells' demise, the scientists put another group of transplanted rats on a fat-restricted diet. A third group was given leptin, a hormone that reduces fat levels by quelling appetite and upping metabolism. In both groups, but especially in the leptin group, more beta cells survived. The differences in the beta cell survival rates among the three groups was directly linked to the amount of fat to which they were exposed.

The researchers concluded that the liver's blood supply is so rich in fats that it's actually toxic to the transplanted beta cells. They also theorized that the insulin produced by the beta cells provokes the liver to synthesize fat around the islets, thus sealing their doom.

Now the researchers are investigating whether it's fat that's killing beta cells in obese people with type 2 diabetes. Meanwhile, they advise that a fat-restricted diet might prolong the lives of transplanted beta cells in humans.

Source: Utah Southwestern Medical Center


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