New Diabetes Treatment May Take Inspiration from Genetically Mutated Mice

A team of geneticists has found that a single gene dysfunction in mice results in the creatures developing fasting hypoglycemia, which is one of the major symptoms of type 2 diabetes.

Type 2 diabetes affects roughly 8 percent of Americans and more than 366 million people worldwide. The researcher's discovery may enable a new treatment for diabetes patients to be developed in the future.

The research focused on a gene known as MADD. If the MADD gene is not functioning properly, insulin is not released into the bloodstream to regulate blood sugar levels. People with diabetes do not produce enough insulin or are resistant to its effects.

Previous research has linked a mutation in the MADD gene with type 2 diabetes in Europeans and Han Chinese.

People with this mutation of the MADD gene had high blood glucose and problems of insulin secretion, which are "the hallmarks of type 2 diabetes," according to Bellur S. Prabhakar, professor and head of microbiology and immunology at University of Illinois at Chicago College of Medicine.

Prabhakar and his colleagues studied the MADD mutation by engineering mice with the gene deleted from their insulin-producing beta cells. These genetically altered mice were all found to have elevated blood glucose levels, which the researchers determined was due to insufficient release of insulin.

"We didn't see any insulin resistance in their cells, but it was clear that the beta cells were not functioning properly," Prabhakar said in a statement. "The cells were producing plenty of insulin, they just weren't secreting it," he said.

Prabhakar, who is the lead author of the research paper published in the journal Diabetes, said that the work shows that type 2 diabetes can be directly caused by the loss of a properly functioning MADD gene alone. "Without the gene, insulin can't leave the beta cells, and blood glucose levels are chronically high," he said.

In the future, the researchers plan to look into effects of a drug that allows for the secretion of insulin in MADD-deficient beta cells.

"If this drug works to reverse the deficits associated with a defective MADD gene in the beta cells of our model mice, it may have potential for treating people with this mutation who have an insulin-secretion defect and/or type 2 diabetes," he said.