Diabetes and the Oxygen Deprived Mouse

Diabetes and the Oxygen Deprived Mouse: Certain oxygen-deprived mice seem to thrive by eating as much as they want, staying lean in the process and avoiding any diabetic symptoms. What scientists learn from these mice may aid in future diabetic care.

According to a press release on the subject these mice, “process fat differently,” said Randall Johnson, professor of biology at the University of California, San Diego, who directed the research, which is published in the April 15 issue of the journal Cell Metabolism. While their normal littermates gain weight, develop fatty livers and become resistant to insulin on a high fat diet, just like overweight humans do, the mutant mice suffered none of these ill effects.”

This report cites a protein called FIH that dictates the response a body has in low oxygen level conditions. The authors of the study indicate drugs can inhibit the protein. The press release stated, “Because the protein influences a wide range of genes involved in development, the scientists were surprised that its deletion improved health.”

“We expected them to die as embryos,” said Na Zhang, a graduate student in Johnson’s lab and lead author of the study. “Then we saw they can survive for a long time.”

“From the beginning I noticed that these mice are smaller, but not sick. These mice seem to be healthy,” Zhang said. The lean mice have a high metabolism, and a common check for insulin resistance, a symptom of diabetes, revealed a super sensitivity to insulin.

“We fed the mice with a very high fat diet – 60 percent fat – just to see how they would respond,” Zhang said. “Mutants can eat a lot, but they didn’t gain a lot of weight. They are less fatty around their middles compared with their littermates.”

In reference to the comparison between the oxygen deprived mutant mice and humans the theory seems to be that with the inhibition of FIH cholesterol levels go down, instances of fatty liver decline and metabolic profiles improve.

Researchers noted that these FIH deprived mice ate more and drank more than mice without the protein deficiency, but according to Johnson the calories went, “To heat generation and an increased heart rate. They also breathe heavily compared with normal mice, taking in 20 to 40% more air. This deep breathing is like exercise for them.”

The protein deficiency was replicated in other mice and found to provide the same response. However, the FIH has to be deprived in virtually all tissue in order to be successful. It was tried in the liver only with limited results.

The press release concludes by saying, “The FIH protein is part of a wide system that responds to low levels of oxygen. The mice behave as if they are breathing thin air. When people travel to higher altitudes, they breathe heavily for a few days, then adjust by producing more oxygen-carrying blood cells. ‘These mice never adjust to the apparent low oxygen,’ Johnson said. ‘They stay in this acute phase of hypoxic response their whole lives.’”

In essence the oxygen deprivation requires more active work to gain the needed oxygen allowing the metabolism to kick into overdrive as the mice develop faster heart rates and quicker breathing techniques. The end result is a greater need for fuel, but a reduced risk for diabetes.

I don’t believe the researchers are suggesting that we cure diabetes by making patients oxygen deprived, but there may be some elements of the research that can assist in the development of new therapies to aid in the struggle against diabetes.