A defect in a single gene can cause insulin to not be released into the bloodstream, leading to type to diabetes, a scientist recently found.
A research team led by Bellur S. Prabhakar, professor and head of microbiology and immunology at University of Illinois at Chicago College of Medicine, found that dysfunction in a single gene called MADD in mice causes fasting hyperglycemia - one of the major symptoms of type 2 diabetes.
In a healthy person, beta cells in the pancreas secrete the hormone insulin in response to increases in blood glucose after eating. Prabhakar isolated several genes from human beta cells, including MADD, which is also involved in certain cancers.
"Small genetic variations found among thousands of human subjects revealed that a mutation in MADD was strongly associated with type 2 diabetes. People with this mutation had high blood glucose and problems of insulin secretion - the hallmarks of type 2 diabetes," said Prabhakar.
To study the role of MADD in diabetes, Prabhakar and his team developed a mouse model in which the MADD gene was deleted from the insulin-producing beta cells.
All such mice had elevated blood glucose levels, which the researchers found 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," said the study reported online in the journal Diabetes.
"The cells were producing plenty of insulin, they just weren't secreting it," it added.
Prabhakar now hopes to investigate the effect 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.