At first glance, type 2 diabetes, in which people lose the ability to control their blood glucose levels, doesn’t seem to have any connection to prions or neurodegenerative diseases. But in people who have this form of diabetes, cells of the pancreas amass clumps of a protein known as islet amyloid polypeptide (IAPP), which is very similar to the β amyloid that accumulates in Alzheimer’s disease. Deposits of the protein may eventually kill many of the β cells in the pancreas that manufacture the hormone insulin.
In the new study, neurobiologist and biochemist Claudio Soto of McGovern Medical School at the University of Texas Health Science Center in Houston and colleagues tested whether IAPP alone could instigate diabetes in mice. The researchers began by culturing pancreatic cells from healthy humans and from young mice that had been genetically engineered to synthesize large amounts of human IAPP. When the scientists added material from the pancreases of old engineered mice that already had diabetes, clumps of IAPP sprouted in the cultured cells. The clumps also appeared when the cells were exposed to lab-synthesized IAPP tangles, the scientists report online today in The Journal of Experimental Medicine.
Soto and his team next tested whether they could induce IAPP clumps to form in live mice. Young rodents that had been genetically modified to crank out human IAPP are normally healthy, but when the scientists injected them with synthetic IAPP or with material from the pancreases of diabetic mice, IAPP conglomerations formed in the pancreas. As with prions, a smidgen of misfolded IAPP acts like a seed that spurs new clusters of the abnormal protein to grow.
The scientists then investigated whether inducing IAPP conglomerations in mice sparked the symptoms of type 2 diabetes. It did. The affected animals’ blood glucose concentrations were higher than those of control animals. And like people with diabetes, the animals had abnormal glucose tolerance tests, which measure their ability to metabolize a dose of the sugar. Even more striking, large numbers of β cells died in each rodent’s pancreas.
.Could diabetes spread like mad cow disease? | Science | AAAS