By studying one family with rare blood sugar disorders, scientists have identified a gene mutation that can give rise to both high and low blood sugar. This discovery could lead to new treatments for diabetes.

Diabetes is a condition in which the body is unable to produce enough of the hormone insulin, or it cannot use it effectively.

As a result, blood sugar levels become too high.

It is estimated that around 30.3 million people in the United States are living with diabetes. Type 2 diabetes is the most common form, followed by type 1 diabetes.

But there are some rarer forms that account for just 1%–4% of cases in the US. These are known as monogenic diabetes, and they arise from a mutation in a single gene that is passed down from one or both parents.

Such mutations impair the function of beta cells, which are cells in the pancreas that secrete insulin.

One of the commonest forms of monogenic diabetes is maturity onset diabetes of the young, which accounts for approximately 2% of all diabetes cases in the US among people under the age of 20.

For this latest study, lead author Prof. Márta Korbonits—of the William Harvey Research Institute at Queen Mary University of London (QMUL) in the United Kingdom—and her colleagues studied a unique family, some members of which had diabetes, while others had insulinomas, or insulin-producing tumors in the pancreas.

Notably, diabetes is characterized by high blood sugar levels, while insulinomas cause blood sugar levels to become too low. How can both of these conflicting conditions run in the same family?

According to Prof. Korbonits and team, a single gene mutation is to blame.

MAFA mutation uncovered

By analyzing the genomes of the family, the researchers were surprised to find a single mutation in the MAFA gene that was present in both the family members with diabetes and those with insulinomas.

The MAFA gene normally regulates the production of insulin in beta cells. A mutation in this gene leads to the production of an abnormal MAFA protein, which seems to be more abundant in beta cells than normal MAFA proteins.

The researchers were able to confirm the presence of the MAFA gene mutation in another family, which also had members with both diabetes and insulinomas.

Overall, the results indicate that a mutation in the MAFA gene may be a cause of both high and low blood sugar levels, but precisely how the mutation causes such conditions remains unclear.

"We believe," explains first study author Dr. Donato Iacovazzo, also of the William Harvey Research Institute at QMUL, "this gene defect is critical in the development of the disease and we are now performing further studies to determine how this defect can, on the one hand, impair the production of insulin to cause diabetes, and on the other, cause insulinomas."

These results—due to be published in the Proceedings of the National Academy of Sciences—represent the first time that a mutation in the MAFA gene has been associated with disease, and the researchers believe that they could pave the way for new treatments for common and rare forms of diabetes.

"While the disease we have characterized is very rare, studying rare conditions helps us understand more about the physiology and the mechanisms underlying more common diseases. We hope that in the longer-term this research will lead to us exploring new ways to trigger the regeneration of beta cells to treat more common forms of diabetes," said study co-author Prof. Sian Ellard, University of Exeter, UK