Gene discovery could help find new treatments for diabetes

Scientists identified a gene mutation leading to high and low blood sugar levels. This discovery could aid the search for new methods for allowing the regeneration of beta cells.

The MAFA gene mutation was found to play a role in both insulinomatosis and diabetes

Scientists find a gene mutation leading to high and low blood sugar levels. This discovery could help find new methods for allowing the regeneration of Beta cells, necessary for the most common types of diabetes.

An estimated 30.3 million individuals in the United States live with diabetes, a condition where the body is unable to produce enough insulin or to use it effectively. Type 2 diabetes is its most common type, followed by type 1 diabetes. The rarer forms of diabetes account for only 1-4% of cases in the United States. Among these is a condition known as monogenic diabetes, which arises from a genetic mutation that impairs the function of beta cells located in the pancreas.

Professor Marta Korbonits, from the William Harvey Research Institute at Queen Mary University of London (QMUL) and her colleagues studied a family where some members have diabetes, insulinomas, or insulin-producing tumors in the pancreas. Diabetes causes blood sugar to rise, while insulinomas cause it to become too low. According to the research team, one single mutation is to blame.

The study aimed to determine the family’s genetics behind these conditions. By analyzing their genomes, the team discovered the MAFA gene in the family members, with autosomal dominant inheritance of diabetes mellitus or insulimatosis. The missense MAFA mutation was identified through exome sequencing and was also found in a second unrelated family that has the same clinical phenotype of diabetes and insulinomatosis. The missense mutation leads to familial insulinomatosis or diabetes by impacting the MAFA protein stability and transactivation ability.

Since the gene causes both insulinomatosis and diabetes, the research team believes that the gene is critical to help in the development of new treatment for the disease. They hope that this research will help pave the way to exploring new ways to trigger the regeneration of beta cells to treat more common forms of diabetes.

Iacovasso D, Flanagan SE, Walker E, et al. MAFA missense mutation causes familial
 insulinomatosis and diabetes mellitus. Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2018. Doi:10.1073/pnas.1712262115