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Could Type 2 Diabetes Be Transmissible ?
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A new study has found a prion-like mechanism that drives type 2 diabetes.

Although the findings are preliminary, new research suggests that type 2 diabetes may be transmissible in a way that is similar to prion disorders such as "mad cow disease."
Type 2 diabetes affects more than 420 million people worldwide, its causes remain largely unknown. However, a new study has uncovered a novel mechanism that may drive the disease. The discovery could change the way we approach type 2 diabetes, both from a research perspective and from a therapeutic point of view.

More specifically, the study investigates the possibility that type 2 diabetes might be caused by a misfolding of islet amyloid polypeptide protein (IAPP).
The research was led by Claudio Soto at the McGovern Medical School in Houston, TX, which is part of the University of Texas Health Science Center in Houston.
The findings, published in The Journal of Experimental Medicine, show that type 2 diabetes shares similarities with a group of transmissible neurodegenerative diseases known as "prion diseases."
Examples of such diseases include bovine spongiform encephalopathy - popularly known as "mad cow disease" - or its human equivalent, Creutzfeldt-Jakob disease.

IAPP in type 2 diabetes
Previous research has shown that up to 80 percent of all type 2 diabetes patients have an accumulation of IAPP in the pancreas' islets. These are small clusters of cells inside the pancreas, which contain, among other cells, insulin-producing beta cells.

IAPP is a peptide hormone that is secreted together with insulin by the pancreatic beta cells. While the effect of this excessive IAPP in type 2 diabetes is not fully known, it is believed that it damages the beta cells, stopping them from producing the insulin that the body needs to lower blood sugar levels.

Examining the 'prion-like' mechanism
Prion diseases get their name from the excessive accumulation of an abnormal form of a so-called prion protein - that is, a cellular protein that occurs naturally in the body. This abnormal form of the prion protein is generated through a mechanism called misfolding. Normally, proteins gain their functional shape through a process referred to as folding.
But when they do not fold correctly, or "misfold," these proteins clump together, forming aggregates such as the ones found in Alzheimer's disease, Parkinson's disease, Huntington's disease, and other neurodegenerative conditions.

Moreover, in some of these diseases, a few of the misfolded proteins can act as "seeds" that trigger other proteins to misfold. In these diseases, the seeds - or abnormal prions - can transmit from one person, or animal, to another.

Prion-like mechanism may cause diabetes
For their research, Soto and his team designed a mouse model wherein the mice's pancreases were genetically modified to express human IAPP.
They injected misfolded IAPP into these mice and found that it triggered the formation of protein deposits, or aggregates, in the mice's pancreases.
Additionally, the mice developed type 2 diabetes symptoms within weeks of having IAPP injected: they lost beta cells and had high blood sugar levels.
Furthermore, the researchers examined the effect of misfolded IAPP in pancreatic islet cultures, taken from healthy humans. There, too, misfolded IAPP triggered the formation of large IAPP aggregates.
Therefore, it appears that misfolded IAPP can, in fact, cause aggregates in a way that is similar to infectious prion disorders.

Although there have been numerous cases of patients who developed type 2 diabetes after organ transplantation, the authors caution against jumping to conclusions.

"Considering the experimental nature of the models and conditions utilized in this study, the results should not be extrapolated to conclude that type 2 diabetes is a transmissible disease in humans without additional studies," Soto warns.

He further comments on the significance of the findings, saying, "Until now, this concept has not been considered. Our data, therefore, [open] up an entirely new area of research with profound implications for public health."

"Perhaps more important than a putative inter-individual transmission, the prion-like mechanism may play a key role in the spreading of the pathology from cell to cell or islet to islet during the progression of type 2 diabetes." - Claudio Soto



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