Misfolded Protein Aggregates May Induce Type 2 Diabetes

A misfolded pancreatic protein may drive symptoms of type 2 diabetes, according to a new study published by The Journal of Experimental Medicine. The study also suggests that the protein may be spread by a mechanism similar to prion diseases, including Creutzfeldt-Jakob disease or mad cow disease.

The CDC recently reported that more than 30.3 million Americans have type 2 diabetes or prediabetes. While many factors have been linked to the condition, the cause of diabetes is unknown.

The authors found that more than 90% of patients with diabetes have abnormal protein deposits in their pancreatic islets, which are clusters of misfolded islet amyloid polypeptide (IAPP), according to the study.

The role of IAPP clusters in diabetes is currently unknown, but the authors hypothesize that they might kill beta cells that produce insulin. If proven, it could mean that type 2 diabetes is similar to Alzheimer’s disease, Parkinson’s disease, and prion diseases, in that it is driven by misfolded protein aggregates, according to the study.

“Until now, this concept has not been considered,” said senior author Claudio Soto, PhD. “Our data therefore opens up an entirely new area of research with profound implications for public health. This 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.”

A major component of these conditions is that a few aggregates act as “seeds” that cause other proteins to misfold until the clusters grow and damage cells. In prion diseases, the authors report that the seeds can be transmitted to individuals, but it is unclear if that is true in diabetes.

The investigators discovered that injecting small numbers of misfolded IAPP aggregates resulted in the development of protein deposits in the pancreases of mice with human IAPP, according to the study.

The authors observed that within weeks, the mice experienced characteristics of type 2 diabetes, including beta cell death and uncontrolled blood glucose levels. They also discovered that misfolded IAPP could also induce IAPP aggregates in pancreatic islets from healthy human patients, according to the study.

The authors concluded that misfolded IAPP may create aggregates in the pancreas and elicit diabetes symptoms. While the authors noted similarities between diabetes and prion diseases, additional studies are needed to determine if it can be transmitted.

“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,” Dr Soto said.