A study conducted at the University of Wisconsin-Madison has identified a gene that could increase susceptibility to diabetes in those who carry it. Researchers discovered the gene in obese mice; it controls a protein called tomosyn-2, which decreases insulin production by the pancreas. The findings were published in the journal “PLoS Genetics,” which published by the Public Library of Science.
Beta cells in the pancreas are responsible for making and releasing insulin into the bloodstream, where it removes glucose from the blood and carries it into cells so that it can be used as energy. Type 1 diabetes is characterized by a lack of insulin while Type 2 diabetes causes an individual to be insulin-resistant. Both diseases cause a wide variety of complications, becoming more severe if they go untreated.
Alan Attie of the University of Wisconsin-Madison headed the study. He commented that the discovery of the gene could be an important development but it’s uncertain whether the gene can be targeted by therapeutics to effectively combat diabetes in insulin.
“It’s too early for us to know how relevant this gene will be to human diabetes, but the concept of negative regulation is one of the most interesting things to come out of this study and that very likely applies to humans,” said Attie.
Researchers used obese mice in the study, which require more insulin to lower blood glucose levels than mice of a normal weight — and the same is true of humans.
“If you can produce that extra insulin – and most people do – you’ll be okay,” said Attie. “You will avoid diabetes at the expense of having to produce and maintain a higher insulin level.”
According to Attie, however, being overweight means that the body is less able to produce the extra insulin required to eliminate elevated glucose levels.
“Most of the type 2 diabetes that occurs in humans today would not exist were it not for the obesity epidemic,” he said.
Researchers on the study compared diabetes-susceptible and diabetes-resistant mice. They found that a single amino acid accounted for the destabilization of tomosyn-2 in the diabetes-resistant mice. That one mutation allowed the diabetes-resistant mice to produce additional insulin to meet the increased demands of obesity.
While the onset of diabetes is a complex process and it is unlikely that a single gene could be targeted to elminate the disease altogether, genetic research into diabetes can eventually illuminate the processes and allow researchers to develop therapies that cut off diabetes at the source. Many scientists agree that genetic factors play about a 50 percent role in an individual’s risk of developing diabetes.
“This study shows the power of genetics to discover new mechanisms for a complex disease like type 2 diabetes,” said Sushant Bhatnagar, co-lead author of the study.
“Now we know there are proteins that are negative regulators of insulin secretion,” said Attie. “Very likely they do the same thing in human beta cells, and it motivates us to move forward to try to figure out the mechanisms behind that negative regulation.”
The researchers disclosed that they had no competing interests that could have affected the results of the study. Attie and his research team bred mice and kept records of results for over a decade to arrive at their findings.