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Protein the "Perfect Storm" for Diabetes and Possible Cure

Posted: Wednesday, July 29, 2009

Researchers have found that the damaging substance begins showing up well before diabetes begins and rises along with blood sugar as the disease progresses. This may be a new target to provide a possible cure for Type 2 diabetes.

In diabetics, factory cells in the pancreas that pump out insulin also produce a destructive substance that can eventually kill the cells that produced it. In a new San Antonio-led study using autopsy results of 150 baboons that died of natural causes, researchers have found that the damaging substance begins showing up well before diabetes begins and rises along with blood sugar as the disease progresses.

The scientists also showed that the same protein is linked to an increase in other cells in the pancreas that tell the liver to make even more blood sugar, creating a "perfect storm" of Type 2 diabetes.

The findings, also help explain why damage to the insulin-producing beta cells occurs in prediabetics, those whose blood sugars are higher than normal but are not considered as having full-blown diabetes.

Baboons become obese and develop Type 2 diabetes like humans. As baboons at Southwest Foundation for Biomedical Research died, they were examined for protein deposits formed by a hormone called islet-amyloid polypeptide, or IAPP.

Those protein deposits kill off the insulin-producing beta cells that also make IAPP.

At the same time, the deposits also seem to lead to growth of alpha cells in the pancreas that produce glucagon -- a substance that tells the liver to release stored blood sugar between meals. But it's not clear if the protein itself creates more alpha cells or if it somehow leads to other changes in the pancreas that allow the alpha cells to thrive.

"When you have an imbalance like in this situation, this is the perfect storm," said Dr. Franco Folli, associate professor of medicine at the University of Texas Health Science Center and the paper's senior author.

"You have a condition in which the beta cells die and the alpha cells proliferate. This is the balance that is basically necessary to have the onset of Type 2 diabetes."

While the protein was present in animals whose blood sugar was only slightly high, it rose along with blood sugar as the disease progressed, Folli said.

Some prediabetics already show signs of eye and kidney damage, and experts have wrestled with how to treat them. An endocrinology group recently developed the first treatment guidelines for this group. And Dr. Ralph DeFronzo, chief of the diabetes division at the health science center and one of the study's co-authors, has argued that many prediabetics should be treated to prevent the beta cells from being destroyed.

Folli said researchers are looking at IAPP as a possible new target for drug treatment, although no known drug affects IAPP levels.

"This is a new pathway to be targeted for a cure for Type 2 diabetes," he said.