Indian-American leads new potential treatment for diabetes
Houston: In a significant discovery, a team of researchers led by an Indian-American has found that a single gene dysfunction in mice results in developing fasting hypoglycemia, one of the major symptoms of Type 2 diabetes.
The discovery by researchers, led by Prof. Bellur S Prabhakar, focused on a gene MADD for the study and may enable a new potential treatment for diabetes patients.
If MADD is not functioning properly, insulin is not released into the bloodstream to regulate blood sugar levels, said Prabhakar, professor and head of microbiology and immunology at University of Illinois at Chicago.
In previous work, 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 in Europeans and Han Chinese.
People with this mutation had high blood glucose and problems of insulin secretion - the "hallmarks of type 2 diabetes", Prabhakar said.
But it was unclear how the mutation was causing the symptoms, or whether it caused them on its own or in concert with other genes associated with Type 2 diabetes.
To study the role of MADD in diabetes, Prabhakar and his colleagues 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," Prabhakar said.
Examination of the beta cells revealed that they were packed with insulin. "The cells were producing plenty of insulin, they just weren't secreting it," he said.
Prabhakar said that the work shows that Type 2 diabetes can be directly caused by the loss of a properly functioning MADD gene alone.
"Without the gene, insulin can't leave the beta cells, and blood glucose levels are chronically high," he said.
In the future, the researchers plan to look into effects 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.
Type 2 diabetes affects roughly 8 per cent of Americans and over 366 million people worldwide. It can cause serious complications, including cardiovascular disease, kidney failure, loss of limbs and blindness.
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