Mutant gene protein may reveal origin of diabetes

Certain mutant gene proteins in the pancreas can turn normal gene proteins bad and lead to insulin deficiency, according to the University of Michigan Health System.

In neonatal diabetes, insulin gene mutations cause misfolding of some proinsulin proteins in pancreatic beta cells. Proinsulin proteins are the precursors of the hormone insulin, which the body needs to convert glucose to energy.

The University of Michigan researchers discovered that these misfolded mutant proteins also cause misfolding of normal proinsulin proteins in beta cells. They hypothesize that this misfolding blocks insulin production.

“Once the 'good' proinsulin turns 'bad,' it cannot be made into insulin and so the beta cells, and then the whole animal, become insulin deficient. The insulin deficiency causes diabetes and from there, things get worse and worse,” said Peter Arvan, MD, PhD, the study's senior author and chief of Metabolism, Endocriniology and Diabetes at the University of Michigan Medical School.

These findings suggest that all forms of diabetes could possibly originate in these mutant genes. The researchers hope that this early research might eventually lead to advances in therapies for diabetes, in particular the development of medicines that protect normal insulin-producing proteins in people with both type 1 and type 2 diabetes.

Proteins are molecules arranged in a particular order as determined by genes. They typically fold into specific shapes. Some scientists believe that misfolding may play a role in common diseases.

In type 1 diabetes, the body does not produce insulin. Only about 5 percent of people with diabetes have type 1 disease. It's usually diagnosed in children and young adults.

The vast majority of Americans living with diabetes have type 2 diabetes. In this type, the body does not produce enough insulin or the cells ignore the insulin needed.

About 25.8 million people in the United States have diabetes. Officials estimate that 7 million people living with diabetes are not diagnosed. About 79 million people have prediabetes.

Source: University of Michigan Health System

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