Could a single gene be responsible for diabetes? In a new study from the University of Illinois at Chicago School of Medicine, researchers show that deficiencies in one beta cell gene can inhibit the body’s ability to control blood sugar uptake. The findings could inspire new treatment against the chronic condition that currently affects millions of people around the world.

When we eat, beta cells in the pancreas secrete the hormone insulin, allowing blood glucose to be absorbed and converted into energy. But for people with diabetes, something in this process backfires, and the blood glucose begins to rise uncontrollably. Patients must for this reason keep a close eye on their glucose levels throughout the day, and inject insulin in response to fluctuations. The new study, which is published in the journal Diabetes, sought to identify a potential genetic basis of this disorder.

According to Bellur S. Prabhakar, previous epidemiological work has illuminated a strong link between type 2 diabetes and a mutation in MADD –– a beta cell believed to be involved in a variety of adverse health outcomes, including cancer. To investigate this link, Prabhakar and his colleagues designed an experiment with mice missing this gene.

The team found that, in mice without the gene, cells tasked with insulin secretion did not do their job properly. Although the cells were packed with the hormone, something appeared to prevent them from releasing it. "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 press release. "The cells were producing plenty of insulin, they just weren't secreting it." 

From this, the researchers concluded that type 2 diabetes –– or, adult-onset diabetes –– may stem from deficiencies in a single gene. Even if their production of insulin is high, this type of diabetic cannot handle glucose fluctuations, as the necessary beta cell-response is simply not there. "Without the gene, insulin can't leave the beta cells, and blood glucose levels are chronically high,” Prabhakar told reporters.

Curing The Incurable

The current study exemplifies the emergence of potential genetic targets that may one day allow physicians to treat conditions currently considered incurable. The most significant example of 2013 is arguably a Washington University School of Medicine study in which researchers show that the same 127 genetic mutations drive the tumor growth in 12 major types of cancer. Hopefully, these efforts will lead to new, effective therapies for cancers, diabetes, neurodegenerative disease, and other treatment-resistant disorders.

For Prabhakar and his colleagues, the next step is to develop a drug that helps a mutated MADD gene back on track. "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," they wrote.

According to the National Institutes of Health (NIH), diabetes currently affects about 25.8 million Americans, or about 8.3 percent of the population. Complications include damage to eyes, kidneys, and nerves as well as an elevated risk of heart disease and stroke. To learn more about the condition and how to manage it, visit the NIH’s online database.

Source:  L.-c. Li, Y. Wang, R. Carr, C. S. Haddad, Z. Li, L. Qian, J. Oberholzer, A. V. Maker, Q. Wang, B. S. Prabhakar. “IG20/MADD Plays a Critical Role in Glucose-Induced Insulin Secretion.” Diabetes, 2013