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Blind cavefish seem to ignore insulin without health consequences


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The Mexican tetra comes in different flavors. In normal river habitats, it’s a small, standard-looking, silvery fish. But some groups within the species have made their home in dark, food-scarce caves. Evolution has quickly rid these groups of their resource-hungry eyes and turned them into pinkish, chubby, blind cavefish—with a bunch of metabolic changes that help them survive in the extreme environment.


A paper in Nature this week reports that the cavefish are resistant to insulin, a condition that can cause damage on its own and is often a precursor to diabetes. But the fish somehow don’t suffer the same kinds of tissue damage that humans do when we have insulin resistance. The authors of the paper, led by Harvard geneticist Misty Riddle, report on how they tried to get to the bottom of the genetic mutations that contribute to this metabolic mystery. Their results show just how much variety exists in how different species respond to insulin—and that studying these fish more could help our understanding of diabetes.

High blood sugar

After you eat something, your blood sugar rises, and your pancreas releases insulin to deal with the increase. The insulin binds to specialized receptors, found on the surfaces of muscle, fat, and liver cells, telling them to absorb glucose from the blood. In between meals when blood glucose levels drop, a different hormone (glucagon) prompts the liver to release its stored glucose back into the blood.


These processes get disrupted by diabetes. In type II diabetes, not enough insulin is produced, or the body doesn’t properly recognize the insulin it makes. The result is insulin resistance, and it means high blood glucose levels persist for longer periods of time. This eventually leads to tissue damage and the host of health problems that come along with type II diabetes.


That is, unless you’re a cavefish, apparently. Adapting to their dark, food-scarce environment has pushed these fish to develop metabolic eccentricities: they have reduced circadian rhythms and lower oxygen consumption, and they store more fat than their surface-dwelling brethren. Riddle and her colleagues have even discovered a new metabolic oddity: cavefish have glucose levels that are all over the map.


After exploring a few possible explanations for this, the researchers dug into published genome sequencing data, finding that the cavefish have a genetic mutation that changes their insulin receptors and leaves them resistant to it. Humans with the same mutation have a severe and dangerous form of insulin resistance known as Rabson-Mendenhall syndrome.


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