An unusual patient is helping scientists study diabetes.
In a paper published today, Stanford researchers report a new way to use fruit flies to sort through the complicated genetics of Type 2 diabetes.
Type 2 diabetes, once known as adult-onset diabetes, is the most common form of diabetes and affects millions of Americans. The condition is partly genetic, and past studies have uncovered many possible risk genes associated with the disease.
Problem is, scientists don’t understand enough about these genes to know which ones are the real culprits.
“There are scores of these genes that have been linked but not proven to have a causative role in diabetes,” said Seung Kim, a professor at the Stanford School of Medicine and the senior author of the study. “No one really knows what most of those [genes] do.”
Although it’s possible to study the genes in mice or in human cells, Kim says it's extremely laborious and expensive. He thinks fruit flies will offer researchers an easier, faster and cheaper way to study the genes.
Type 2 diabetes is characterized by the body’s inability to properly create or respond to insulin, a molecule that regulates blood sugar. Practically all animals, including fruit flies, use insulin to control how they metabolize sugar. And while flies may seem a far cry from humans, Kim says they are a reasonable experimental stand-in for studying the disease.
To study diabetes in flies, Kim first needed a way to monitor the insulin in the tiny creatures' blood.
“Because the size of a fruit fly is obviously very small, it doesn’t have much blood,” Kim explained. “Measuring insulin in fruit flies has been a real challenge in the field, and something we’ve been trying to overcome for several years.”
Kim and his team figured out how to add a molecular label to fruit fly insulin that allowed them to reliably measure very low levels of insulin in extremely small samples of fly blood.
They are now using this technique to study different risk genes associated with Type 2 diabetes. In the current study, they examined two such genes. One gene controlled how much insulin was produced in the fly, while the other regulated the amount of insulin circulating in the fly’s blood. These results provide useful information about how each gene could uniquely relate to diabetes.
“I think this a very nice example of using the power of Drosophila [fruit fly] genetics to try to gain insights into human disease,” said Michael German. German is the Clinical Director of the UCSF Diabetes Center and was not involved in the study.
German points out that fruit flies are just the first step toward figuring out how diabetes works in humans. “Ultimately anything that you find out from flies you then have to confirm in mammals and in humans,” he said.
But using flies as an experimental model is a good starting point.
“I think that sometimes people undervalue these kinds of models,” says German. “They really are remarkably powerful, and we can find things in these models that we would never find if we just tried to study humans, or if we just tried to study mice.”
Moving forward, Kim will use his fruit fly system to study the many human genes associated with Type 2 diabetes. His experiments will help researchers prioritize which genes to focus on in more challenging experimental systems -- such as mouse and human cells -- to ultimately develop new approaches to treating diabetes.
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