Burning More Fat – Less Glucose May Lead To Diabetes

“The circadian clock works by turning certain genes on and off as the 24-hour cycle progresses. HDAC3 is a key connection between the circadian clock and gene expression,” said Sun.

“Our previous work showed that HDAC3 helps the liver alternate between producing glucose and producing lipid. In this work, we studied how HDAC3 controls the use of different fuels in skeletal muscle,” Sun added.

Skeletal muscles, the voluntary muscles, are important in the control of blood glucose in the body. They consume most of the glucose and if they develop insulin resistance and consequently are not able to use glucose, then diabetes likely will develop.

To study the role of HDAC3 in mouse skeletal muscle, Sun and colleagues genetically engineered laboratory mice to deplete HDAC3 only in the skeletal muscles.

Then they compared these knocked out mice with normal mice regarding how their muscles burn fuel.

When normal mice eat, their blood sugar increases and insulin is released, which stimulates muscles to take in and use glucose as fuel.

“When the knocked out mice ate, their blood sugar increased and insulin was released just fine, but their muscles refused to take in and use glucose. Lacking HDAC3 made the mice insulin resistant and more prone to develop diabetes,” Sun said.

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