A new study suggests type 2 diabetes progresses, or perhaps begins, in a manner similar to prion diseases like mad cow disease.
A new study shows that key symptoms of type 2 diabetes (T2D) can be induced using a mechanism similar to that of prion diseases like Creutzfeldt-Jakob disease (mad cow disease). The findings could point the way to new treatment options, and may have implications for our understanding of how the disorder begins.
Researchers from the McGovern Medical School at the University of Texas Health Science Center, in Houston, published a study this month reporting that the main features of T2D can be sparked by misfolded pancreatic protein aggregates.
Misfolded protein aggregates also act as a trigger in prion diseases, causing the transformation of normal proteins into abnormal proteins and resulting in the buildup of toxic substances that ultimately destroy neurons in the brain, Claudio Soto (pictured), PhD, a professor of neurology at the University of Texas, said.
These protein aggregates can transmit prion diseases from animal to human or human to human.
Soto runs a lab focused on neurodegenerative disorders associated with misfolded protein aggregates in the brain. He and his colleagues decided to look at T2D because past research has suggested that the loss and dysfunction of beta cells in diabetics may be related to the accumulation in the pancreas of misfolded islet amyloid polypeptide (IAPP), a 37-amino-acid peptide hormone mainly produced by beta cells. Soto said 90% of T2D patients have aggregates of misfolded IAPPs, and these aggregates begin to accumulate even before diagnosis of the disease.
“Interestingly, IAPP aggregates share similar structural features and mechanism of aggregation with prion aggregates,” Soto said. “Thus, our working hypothesis was that pancreatic IAPP aggregates can be transmitted by a prion-like mechanism, leading to some clinical and pathological abnormalities typical of T2D.”
Soto and his colleagues tested the hypothesis by injecting small amounts of these aggregates into mice expressing human IAPP. The mice soon began showing symptoms of T2D, such as the loss of pancreatic beta cells and increased glucose levels.
The researchers also found that depositing small amounts of misfolded IAPP into pancreatic islets isolated from healthy human donors sparked the formation of large IAPP aggregates.
“Our results showing that induction of IAPP misfolding is sufficient to produce the main symptoms of the disease in the absence of any other process (such as high-fat diet or disruption of insulin signaling) suggest that IAPP misfolding and aggregation has an important role in the pathogenesis of T2D,” Soto said.
In theory, Soto’s research suggests that T2D could actually be transmittable from human to human, but Soto said the research is too experimental and too early to draw such a broad conclusion.
However, the study does provide important information that could steer researchers to develop therapies to better control or stop the disease and its effects.
“We believe development of agents that can prevent IAPP aggregation or capture already formed IAPP aggregates will not only stop further damage of the islets but also may restrict the spreading of disease pathology from islet to islet,” Soto said.
The study could also help doctors more quickly detect the disease.
“Indeed, the prion-like feature of IAPP aggregates may be utilized to develop a test that can detect people who might be on the way to develop the disease through a simple blood test," Soto said.
The study, “Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism,” was published this month in The Journal of Experimental Medicine.