Protein discoveries are good news for type 2 diabetes treatment

by Barbara Hewitt on July 29, 2014

Type 2 diabetics have an excess of a protein called islet amyloid polypeptide, or IAPP, which could contribute to the destruction of insulin producing cells in the pancreas, scientists have discovered.

What causes this accumulation of IAPP in pancreatic beta cells of people with diabetes has remained a mystery, but a team of researchers from the Larry L. Hillblom Islet Research Centre in the United States may have found an answer in autophagy, a process that clears damaged and toxic proteins from cell.


IAPP may contribute to the destruction of insulin producing cells in the pancreas

Led by Dr. Peter Butler, professor of medicine at the University of California Los Angeles, the study found that autophagy prevents the accumulation of toxic forms of IAPP in people who do not have type 2 diabetes. In those with Type 2 diabetes, the process appears to not work properly, contributing to the destruction of beta cells. As the body’s insulin producers, beta cells play a key role in maintaining healthy blood sugar levels.

“Only a few previous studies have reported that autophagy is important for beta cell function and survival. Those studies, however, were not conducted to address the role of this process in the regulation of the amyloidogenic protein, which is an important contributor to type 2 diabetes,” said co-author Safia Costes, a research scientist at the Hillblom Center.

Investigators found that autophagy plays a role in clearing IAPP from pancreatic beta cells by using three experimental models: pancreatic beta cells, isolated pancreatic islets from mice that express the human form of IAPP, and human islets.

To corroborate the findings, the researchers also developed a novel mouse model that was deficient for autophagy specifically in beta cells with expression of the human form of islet amyloid polypeptide. They found that mice that had beta cells in which autophagy didn’t work properly showed elevated levels of toxic IAPP, which led to the death of the beta cells. As a result, those mice developed diabetes.

“The goal of our work is to understand the cellular mechanisms responsible for beta cell destruction so that we can identify the best targets for beta cell protection. This would aid the development of the next generation of treatments as well as combination therapies for type 2 diabetes,” explained Costes.

The study also confirmed similarities between type 2 diabetes, Alzheimer’s and other neurodegenerative diseases that are marked by an accumulation of toxic forms of amyloid proteins, she pointed out. “This demonstrates the importance of autophagy in clearing out these harmful proteins to prevent both type 2 diabetes and Alzheimer’s,” she added.

Meanwhile, scientists have discovered that a protein which is already naturally produced in the body has cured type 2 diabetes in mice; they are confident that it could be easily replicated in humans.

The protein, called FGF1, already plays a role in human cell growth and tissue repair, but never usually enters the bloodstream. However, a team at the Salk Institute in La Jolla, California, found that when the protein was injected into a muscle and interacted with blood, it dramatically reduced blood sugar levels in the mice.

Crucially, the protein also seems to reverse the root cause of type 2 diabetes, making the metabolic system react to insulin when it had been failing to do so.

In obese mice with the disease, just one injection of the protein restored blood sugar levels to a healthy range for more than two days and continued treatment restored it completely.

‘”This is a big deal as this treatment is very simple to make. It offers a new method to control glucose, in a powerful way. The fact that simply reintroducing the protein to the body in a different way had such an impact was quite surprising,” said the institute’s Professor Ronald Evans.

The opinions expressed in this article do not necessarily reflect the views of the Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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