Are Prions Involved with Type 2 Diabetes?

[BillTre]

This Science news article discusses mouse research which indicates prion involvement.
Prion like clumps of islet amyloid polypeptide are found in humans with type 2 diabetes.
When injected into healthy mice amyloid clumps formed and the mice developed diabetic symptoms.

Prions are mis-folded versions of a normally encoded protein that can propagate their mis-folded weirdness to otherwise normal proteins encoded by the same gene. They are involved in brain diseases like Mad Cow Disease, Kuru, and Creuztfeldt-Jacob disease.
If transferred to a different individual, prions can propagate their disease state to the new hosts (if the new animal has the normal protein present).

 

[Ygggdrasil]

Here's a link to the relevant publication:
Mukherjee et al. 2017 Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism. J. Exp. Med. Published online Aug 1, 2017. doi:10.1084/jem.20161134

Abstract:

Although a large proportion of patients with type 2 diabetes (T2D) accumulate misfolded aggregates composed of the islet amyloid polypeptide (IAPP), its role in the disease is unknown. Here, we show that pancreatic IAPP aggregates can promote the misfolding and aggregation of endogenous IAPP in islet cultures obtained from transgenic mouse or healthy human pancreas. Islet homogenates immunodepleted with anti-IAPP–specific antibodies were not able to induce IAPP aggregation. Importantly, intraperitoneal inoculation of pancreatic homogenates containing IAPP aggregates into transgenic mice expressing human IAPP dramatically accelerates IAPP amyloid deposition, which was accompanied by clinical abnormalities typical of T2D, including hyperglycemia, impaired glucose tolerance, and a substantial reduction on β cell number and mass. Finally, induction of IAPP deposition and diabetic abnormalities were also induced in vivo by administration of IAPP aggregates prepared in vitro using pure, synthetic IAPP. Our findings suggest that some of the pathologic and clinical alterations of T2D might be transmissible through a similar mechanism by which prions propagate in prion diseases.

 

[jim mcnamara]

@BillTre - are you positing transmission of Type II somehow? I do not think the research supports that. Just to be clear.

 

[BillTre]

@BillTre - are you positing transmission of Type II somehow? I do not think the research supports that. Just to be clear.

I am not proposing that type 2 diabetes is normally caused by transmission of these amyloid clumps, however it does seem to occurring in mouse experiments where it is injected.
I am however concerned about possible accidental transmission of it through things like transplants. I am currently a recovery technician for an eyebank and am aware of the safeguards they use. Organ transplants are a well known way for potential infectious agents and cancers to be tranfered from one (dead) individual to another. Thus donors are carefully screened for many potential problems which rule them out as donors. These include certain diseases, cancers, and most relevant here, prion based (or associated) diseases like Mad Cow disease, Kuru, Alzheimer disease, Parkinson's disease, and similar brain diseases. Type 2 diabetes is not yet on that list since this finding was only recently reported.
I suspect that will change fairly soon.

 

[Fervent Freyja]

I think this study implies that it has found the mechanism for how some diseases may propagate from cells to other cells, organ tissues, and systems through misfolded proteins during the disease process. I think it’s really just describing a phenomenon that occurs at a scale of proteins sizes here, of 2-10 nm, so this is giving us one of the smallest scale correlations with disease yet. This is likely the primary mechanism in which some diseases spread throughout one individual and one therapeutic treatment for it could be protein aggregation quality control. They could have selected a different disease to study in order to show the same findings. It also makes me wonder if aggregation of misfolded proteins could be correlated with the aging process. The study claims itself an exciting find, but I think it’s near groundbreaking! So much more could be done if only it weren't for the current limitations in imaging or detecting misfolded proteins and also diagnosing prion diseases en vivo.

A neat read: The theoretical bio-physical model for protein misfolding

As an aside, It does bring about the question of whether or not many known diseases, like diabetes, where misfolded proteins are involved, could also be considered an infectious transmittable disease acquired in certain circumstances and whether or not it threatens public health. But then, I think more studies need to determine whether or not this only happens under experimental conditions. To me, the experimental conditions in this study don't seem to mimic any manner in which a person could naturally acquire enough of the misfolded proteins to cause diabetes- short of an organ transplant or type of blood transfusion. I would like to see some studies done for oral transmission. I do now wonder whether any misfolded protein in prion-diseased plants, foods, or animals can be infectious by ingesting them. I also wonder if misfolded proteins are transferred to a fetus during pregnancy and if the mother has a condition like diabetes and whether or not that transfer can be correlated with developing diabetes later on. If so, could therapy be done in utero to lessen the likelihood of developing it?

 

[BillTre]

I would like to see some studies done for oral transmission. I do now wonder whether any misfolded protein in prion-diseased plants, foods, or animals can be infectious by ingesting them.

There was plenty of concern about oral transmission of Mad Cow disease when that scare was going on.
Oral transmission to cows and humans was fro eating meat and neural tissue.