Researchers draw new findings on cause of insulin resistance

Tue, 10 Jun 2014
Researchers have learned how a high calorie diet leads to low availability of oxygen for cells which in turns leads to increased inflammation, insulin resistance and type 2 diabetes.

The research team, from the University of California, San Diego (UCSD), showed how the sequence of events develop in mice and are confident that a similar process will also occur in humans.

The researchers fed the mice a high fat, high calorie diet to bring on obesity and then monitored a number of changes within the mice. A high calorie diet, together with obesity is known to lead to high levels of lipids in the blood but the researchers went on to observe that the high levels of blood lipids led to a protein called adenine nucleotide translocase 2 (ANT2), in fat cells, being activated.

The activation of this protein uses up oxygen, substantially reducing the amount of oxygen available to the rest of the fat cell. The inadequate availability of oxygen (hypoxia) for the cells triggers a protective response leading to inflammation. Over time, the continual presence of inflammation results in the development of insulin resistance.

The protective sequence of events involves a bit more science. When the fat cells enter a state of hypoxia), this causes a protein called HIF-1alpha to release a further set of proteins called chemokines which set off the inflammation.

The researchers note from their findings that there are two new targets for treatment as a result of their findings. Either to inhibit the activation of ANT2, earlier on in the train of events, or to inhibit the action of HIF-1alpha that starts the inflammatory process.

Whilst inhibiting the response of either of these sets of protein could potentially hold back the development of insulin resistance and type 2 diabetes, the research will be needed to see whether there are other negative outcomes from doing so.
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