Will ‘diabetic’ fruit flies lead to new treatments?

Scientists have mapped the signaling processes insulin uses in fruit flies. The finding sheds light on how diabetes may alter these processes in humans.

An estimated one-third of the US population has diabetes or the elevated blood sugar associated with pre-diabetes. The study suggests fruit flies may be able to help address this issue. Insulin signaling is an important process for these creatures; past studies have shown that the natural hormone insulin controls growth and development of the fly.

Additionally, fruit flies raised on a high-sugar diet consisting solely of bananas can actually develop a diabetic-like state, with metabolic dysfunction similar to humans, says David Arnosti, biochemistry professor and director of the Gene Expression in Development and Disease Initiative at Michigan State University and the study’s senior author.

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As an extension of these past findings, Yiliang Wei, a graduate student in Arnosti’s lab and study coauthor, focused on the insulin receptor protein, which binds to insulin and regulates its effects.

“This regulation is similar to the volume control on a hearing aid,” Arnosti says. “If you turn it way down, it doesn’t matter how loud someone shouts at you.”

If the volume is too far down, this low expression may be linked to diabetes as well as Alzheimer’s disease. Cranking up the volume, or overexpression, may actually give cancer cells a growth advantage. Balancing that expression sweet spot, so to speak, involves some complex circuitry—molecular wiring discovered by the team.

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Little was known about how levels of this protein were regulated before the researchers mapped its controlling circuits. One surprising finding was the large number of genetic switches controlling expression of the receptor, which had been previously assumed to possess rather simple regulation. The structure and function of this circuitry is likely to have been sculpted by evolutionary selection.

The researchers predict that the human gene will be similarly regulated, which could open a new chapter in diabetes research to find ways to modulate insulin signaling through control of the receptor, Arnosti says.

The National Institutes of Health funded the research, which appears in the journal Development.

Source: Michigan State University

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