DIABETES could be triggered by a rogue prion-like protein, according to a
controversial new theory.
Garth Cooper, a molecular biologist at the University of Auckland, believes
that adult onset or type II diabetes, which affects tens of millions of people
worldwide, is caused by the misfolding of a protein called amylin. If he’s
right, it could be possible to create a “vaccine” to prevent the disease. “If it
works, it may even allow the insulin-producing cells to regrow,” says
Cooper.
Like insulin, amylin is produced by beta cells in the pancreas. It helps to
regulate glucose use in muscles. At least 90 per cent of people with type II
diabetes have large deposits of amylin fibrils in beta cells. Amylin can kill
beta cells in the test tube, and Cooper says that the rate of cell death closely
matches the build-up of misfolded amylin.
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He has also found that mice given the human gene for amylin develop diabetes
and die. By contrast, mice engineered to produce a slightly different version of
amylin that does not misfold don’t get diabetes.
Cooper, who presented his results last week at the International Union of
Physiological Sciences conference in Christchurch, New Zealand, says amylin
fibrils build up when the molecule misfolds. “The cells appear to be able to
sense these aggregates and switch on a death program,” says Cooper.
These aggregates closely resemble the deposits found in prion diseases such
as vCJD, Cooper says. And if misfolded amylin is added to a solution of normal
amylin, it triggers aggregation, like a prion. There’s no evidence that
misfolded amylin is infectious in the same way as BSE and vCJD, but Cooper says
this can’t be ruled out. “I don’t think you can say for certain that it isn’t
contagious, a la prion. I don’t think we know enough to be sure.”
But not everyone is convinced. “Amylin is controversial,” says Roger Unger, a
diabetes researcher from the University of Texas Southwestern Medical Center. He
points out that amylin is not the only protein that can trigger diabetes in
animals.
The conventional view is that type II diabetes begins when muscle and fat
become resistant to insulin. The body has to increase insulin production to
compensate, eventually killing or exhausting the beta cells, and making insulin
injections necessary. In the vast majority of cases, obesity appears to lead to
the insulin resistance.
“But there are lots of insulin-resistant people walking around—obese
people—who do not get diabetes,” responds Bruce Verchere from the
University of British Columbia, who has worked on amylin. He argues that type II
diabetes must require both insulin resistance and some underlying defect in the
beta cells. “I think the misfolding hypothesis is as good as any other one,” he
says.
However, Unger points out that if you feed normal mice and rats a high-fat
diet they will develop diabetes but don’t get amylin aggregates. Cooper and
Verchere argue that this is not the same as the severe form of disease that
leads to insulin dependence in humans.