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鈥檚
right, it could be possible to create a 鈥渧accine鈥� to prevent the disease. 鈥淚f it
works, it may even allow the insulin-producing cells to regrow,鈥� 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.
Advertisement
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鈥檛 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. 鈥淭he cells appear to be able to
sense these aggregates and switch on a death program,鈥� 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鈥檚 no evidence that
misfolded amylin is infectious in the same way as BSE and vCJD, but Cooper says
this can鈥檛 be ruled out. 鈥淚 don鈥檛 think you can say for certain that it isn鈥檛
contagious, a la prion. I don鈥檛 think we know enough to be sure.鈥�
But not everyone is convinced. 鈥淎mylin is controversial,鈥� 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.
鈥淏ut there are lots of insulin-resistant people walking around鈥攐bese
people鈥攚ho do not get diabetes,鈥� 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. 鈥淚 think the misfolding hypothesis is as good as any other one,鈥� he
says.
However, Unger points out that if you feed normal mice and rats a high-fat
diet they will develop diabetes but don鈥檛 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.