Monday, March 19, 2018

Does Amyloid Clog Beta Cells?

When the beta cells produce insulin, they also produce a protein called IAPP. This stands for islet amyloid polypeptide, and the IAPP is secreted along with the insulin. IAPP is also known as amylin.

Amyloids are proteins that tend to clump when present in excess, and various amyloids contribute to diseases such as Parkinson's (alpha-synuclein clumps) and Alzheimer's (beta-amyloid clumps). The IAPP also clumps, and this causes the beta cells to decline and eventually die, resulting in diabetes.

Now researchers have found where the clumping occurs. It seems be in the tubes that let newly synthesized proteins leave the site of their synthesis (the endoplasmic reticulum) and emerge into the cytoplasm. When these tubes are clogged, insulin can't be released and the whole system gets gummed up.

One interesting thing is that the clumping of amyloids occurs more often when the proteins are present in excess. This means that if you're producing a lot of insulin, you're also producing a lot of IAPP, and the probability of amyloid clumping increases.

"What happens is that as demand for insulin increases, you get more and more IAPP production, and the more you make, the more likely it is to aggregate,” says the lead author of the cited paper Can Kayatekin. “So, the idea is that as you make more IAPP, it starts poisoning the very cells that are producing it.”

Now, what makes you produce a lot of insulin? Eating a lot of carbohydrate, of course. So this could be one way in which high-carbohydrate diets can increase the risk of diabetes.

However, ascertaining where the clogging occurs wasn't the only thing these researchers found. They also found an unclogger called STE24 in yeast and ZMPSTE24 in humans that snips off the clogging IAPP and opens up the channel again. This article has a nice illustration of the declogger.

This research like so much, alas, has no immediate application except to confirm the idea that a very high carbohydrate diet is probably not good for anyone. Sometimes it's the basic research that eventually leads to real advances in treatment, and further research could lead to methods of getting  unclogging enzymes to beta cells so insulin production could go on as it should.

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