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New insulin-decreasing hormone discovered, named for goddess of starvation

530468355_133d4da701_zLimos, the Greek goddess of starvation, must have relied on limostatin, the eponymous hormone recently discovered by Stanford researchers, to survive hunger.

She was clearly not well fed. As Ovid writes: "Her hair was coarse, her face sallow, her eyes sunken, her lips crusted and white; her throat scaly with scurf. Her parchment skin revealed the bowels within..."

Limostatin slashed her insulin levels, keeping nutrients in her blood so they could be used. Without limostatin, humans develop diabetes-like symptoms such as low blood sugar and a tendency toward obesity.

From our press release describing the Stanford work:

The researchers first discovered limostatin in fruit flies but then quickly identified a protein with a similar function in humans.

“Starvation or famine is an ancient, ever-present specter faced by all living organisms,” said Seung Kim, MD, PhD, professor of developmental biology. “The ways to deal with it metabolically are likely to be ancient and conserved. This research clearly connects the dots between flies and humans, and identifies a new potential way to regulate insulin output in humans.”

The researchers discovered limostatin by following a series of "biological breadcrumbs:"

Kim and his colleagues withheld food from their laboratory fruit flies for 24-28 hours and looked to see which genes were highly expressed during this time. They narrowed the list to those genes that encoded proteins resembling hormones, which are special signaling molecules that circulate throughout the body to affect the function of distant cells. They observed that one of these, limostatin, caused characteristics of insulin deficiency when overexpressed in flies...

Once the researchers had identified the receptor for limostatin in fruit flies, they looked to see if it resembled any human protein. A trail of biological breadcrumbs led them to the receptor for a protein called Neuromedin U. The protein is produced in the brain, and controls a variety of physiological responses including smooth muscle contraction, blood pressure control, appetite and hormone function in humans.

Based on their experiments in fruit flies, Kim and his colleagues expected that Neuromedin U might also be important in insulin regulation. They found that the protein is also expressed in the stomach and intestines, and the Neuromedin U receptor is found on insulin-producing beta cells in the pancreas. Neuromedin U and its receptor appeared to neatly connect nutrient sensing in the gut with insulin-producing cells elsewhere in the body.

Previously: Tiny fruit flies as powerful diabetes model, Beta cell development explored by Stanford researchers and Correspondence on the discovery of insulin
Photo by William Murphy

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