'Diabetic flies' can speed up disease-fighting research

November 6, 2013, University of Maryland
Tagging of the human GLUT4 protein in genetically altered fruit flies shows that in response to insulin, GLUT4 travels from cells' interiors to their membranes where it captures glucose. In two forms of microscopy, the fluorescent GLUT4 cells illuminate the flies' cell membranes. Credit: Georgeta Crivat

In a finding that has the potential to significantly speed up diabetes research, scientists at the University of Maryland have discovered that fruit flies respond to insulin at the cellular level much like humans do, making these common, easily bred insects good subjects for laboratory experiments in new treatments for diabetes.

The common fruit fly Drosophila melanogaster looks like a sesame seed with wings, produces offspring by the thousands, and lives for around a month. These creatures don't resemble humans in any obvious way, but they share more than sixty percent of our genetic code. And scientists like UMD's Leslie Pick and Georgeta Crivat are finding that those similarities control basic biological processes that work alike in both species.

Drosophila melanogaster is easy to breed, raise and study in the laboratory, so it's widely used in research. Pick, chairman of the UMD Entomology Department, conducts experiments that use information about the fruit fly's relatively simple genome to illuminate biological processes in humans. Her recent research focuses on whether use the hormone the same way humans and other mammals do.

"We hope to use all the genetic tools we have available for flies, and the fact that we can breed them in huge numbers, very fast, to set up efficient screening tests for assessing new diabetes treatments," Pick said.

In a new study published Nov. 6 in the peer-reviewed online journal PLOS One, Pick and her co-authors found the basic mechanisms that humans use to regulate blood sugar – the process that goes awry in diabetes – are indeed shared with flies.

'Diabetic flies' can speed up disease-fighting research
The fruit fly on the right, genetically altered to disable insulin-like genes and fed a high sugar diet, has symptoms comparable to type 2 diabetes in humans. It is smaller and less able to reproduce than the normal fruit fly on the left, but healthy enough for use in testing diabetes treatments Credit: Jingnan Liu and Hua Zhang

In humans, insulin controls the production and movement of glucose, the form of sugar that fuels mammalian cells. The movement of glucose into individual cells begins when insulin binds to a specialized insulin receptor on a cell. That causes a sugar transporter called GLUT4 to move from the cell interior to its membrane, allowing glucose to flow through the membrane, moving from the bloodstream into the cell. In diabetics, this process fails and sugar accumulates in the blood. In the main types of diabetes - Type 1, in which the body cannot produce insulin, and Type 2, in which the cells stop responding to insulin – high blood sugar levels can gravely damage many organs. The disease is one of the world's most serious health problems.

Fruit flies' systems are very different than humans. Glucose is not their main form of sugar, and they don't have blood like mammals do, so researchers were not sure whether insulin played a role in their cells that is similar to humans. But in a 2009 experiment, Pick and colleagues used genetic engineering techniques to disable five insulin-like fruit fly genes.

The resulting "diabetic flies" had many symptoms of diabetes in humans, Pick said. "They were very, very small and sluggish; they had decreased body fat and higher levels of circulating blood sugar; and they did not reproduce very well." Other researchers trying to understand diabetes have performed similar experiments on mammals, which usually did not survive the genetic alteration, Pick said.

"The flies are not fine, but they do live," Pick said. That meant more diabetes-related experiments, using flies instead of mammals, might be possible.

To be sure, the researchers needed to know whether the cellular processes taking place were the same in both species. Pick and her colleagues turned to Samuel Cushman of the National Institutes of Health, the co-discoverer of the glucose transport process involving GLUT4 in humans. Combining their expertise, the two research teams inserted GLUT4 into fruit flies, using a fluorescent tag to mark the GLUT4 molecules.

To the scientists' surprise, although this protein is foreign to the fruit flies, their cells moved GLUT4 to the cell membrane exactly as human cells do in response to insulin. Under a high powered microscope that picks up the fluorescent GLUT4,"You can actually track its movement onto the cell membrane."

"It's pretty amazing," Pick said. "We hoped that would happen, but there are so many differences between flies and mammals that we ourselves were skeptical."

The researchers' next step is to find the sugar transporter that fills the role of GLUT4 in fruit flies, Pick said, and "to use the fly model to see if we can screen for compounds that promote sugar uptake, alone or working together with insulin, to treat diabetes more effectively."

Explore further: Blocking sugar intake may reduce cancer risk or progression in obese and diabetic people

More information: Georgette Crivat, Vladimir A. Lizunov, Caroline R. Li, Karin Stenkula, Joshua Zimmerberg, Samuel W. Cushman and Leslie Pick, "Insulin stimulates translocation of human GLIUT4 to the membrane in fat bodies of transgenic Drosophila melanogaster," published in PLOS One Nov. 6, 2013. dx.plos.org/10.1371/journal.pone.0077953

Related Stories

Blocking sugar intake may reduce cancer risk or progression in obese and diabetic people

August 1, 2013
Blocking dietary sugar and its activity in tumor cells may reduce cancer risk and progression, according to researchers from the Icahn School of Medicine. The study, conducted in fruit flies and published in the journal Cell, ...

Brain may play key role in blood sugar metabolism and development of diabetes

November 6, 2013
A growing body of evidence suggests that the brain plays a key role in glucose regulation and the development of type 2 diabetes, researchers write in the Nov. 7 issue of the journal Nature. If the hypothesis is correct, ...

Hormone in fruit flies sheds light on diabetes cure, weight-loss drug for humans

August 9, 2012
Manipulating a group of hormone-producing cells in the brain can control blood sugar levels in the body – a discovery that has dramatic potential for research into weight-loss drugs and diabetes treatment.

Team unlocks secrets of diabetes drug: How and why metformin needs to interact with insulin to be effective

November 3, 2013
About 120 million people around the world with Type 2 diabetes – and two million in Canada – take the drug metformin to control their disease.

Glucose uptake relies on newly identified protein

September 6, 2011
All cells need glucose (sugar) to produce the energy they need to survive. High glucose levels in the bloodstream (such as occur after a meal), trigger the pancreas to produce insulin. In turn, muscle and fat cells respond ...

Recommended for you

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

Scientists unleash power of genetic data to identify disease risk

January 16, 2018
Massive banks of genetic information are being harnessed to shed new light on modifiable health risks that underlie common diseases.

Blood-vessel-on-a-chip provides insight into new anti-inflammatory drug candidate

January 15, 2018
One of the most important and fraught processes in the human body is inflammation. Inflammatory responses to injury or disease are crucial for recruiting the immune system to help the body heal, but inflammation can also ...

Molecule produced by fat cells reduces obesity and diabetes in mice

January 15, 2018
UC San Francisco researchers have discovered a new biological pathway in fat cells that could explain why some people with obesity are at high risk for metabolic diseases such as type 2 diabetes. The new findings—demonstrated ...

Obese fat becomes inflamed and scarred, which may make weight loss harder

January 12, 2018
The fat of obese people becomes distressed, scarred and inflamed, which can make weight loss more difficult, research at the University of Exeter has found.

Optimized human peptide found to be an effective antibacterial agent

January 11, 2018
A team of researchers in the Netherlands has developed an effective antibacterial ointment based on an optimized human peptide. In their paper published in the journal Science Translational Medicine, the group describes developing ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.