Here’s a paper that will not calm anyone down about the possibility of prion-like diseases. Those, as many will know, are spread by misfolded proteins that, on contact, template others to follow their example. I last wrote about this field a couple of years ago, when examples appeared of transmissable amyloid pathology in humans, spread by surgical instruments. This latest work (commentary here at Science) is also amyloid-related, specifically IAPP (islet amyloid polypeptide). That forms a protein aggregate that’s commonly found in the pancreatic tissue of patients with type 2 diabetes, and as is usual in these things, no one’s ever been sure if diabetes gives you amyloid (the majority view over time) or if amyloid gives you diabetes (a hypothesis that’s apparently been gaining ground – here’s a review from the same group).
Alarmingly, this paper has evidence for the latter case. If you take mice that are transgenic for the human form of IAPP, and inject them with pancreatic homogenate containing the IAPP aggregate, they rapidly start showing deposits of the same protein precipitate themselves. And then they start developing symptoms strongly reminiscent of diabetes: elevated glucose levels, impaired glucose tolerance, changes in beta-cell mass, and so on. The same thing happens with injections of purified synthetic IAPP, so it’s not some other factor in the pancreatic mixture. Otherwise, there were no abnormalities in either gross organ pathology or histopathology. Injecting other amyloidogenic proteins (such as tau) had no effect.
So how does this fit in with the widely accepted view that insulin resistance is a key factor in type 2 diabetes? The authors think it’s all part of the same picture – insulin resistance might come on first (through mechanisms that are very much open to argument), but the forced overproduction of insulin that it brings on also produced more IAPP, giving the aggregation a chance to really kick in and cause still more damage.
The big question is whether this mechanism is actually operating out here in the real world. It would seem difficult to transmit pancreatic proteins from one person to another, wouldn’t it? On the other hand, it’s hard to know just how much of the protein aggregate one needs to be exposed to for trouble to start. I would tend to be skeptical of this as a means for type 2 diabetes to actually spread in the population, since it would seem that environmental and genetic factors are enough to explain things, patient by patient. I mean, you look at the figures for obesity over the last few decades, and it’s hard to make the case for diabetes being this mysterious scourge that came out of nowhere. But I can’t rule this idea out completely, and I definitely think it needs more investigation. At the very least, it could be telling us how diabetic pathology might spread inside any given individual, once it gets going.