Fatty diets behind onset and severity of diabetes

Scientists have linked high-fat diets to a sequence of molecular events responsible for the onset and severity of diabetes.

In studies spanning mice and humans, the team discovered a pathway to disease that is activated in pancreatic beta cells, and then leads to metabolic defects in other organs and tissues, including the liver, muscle and adipose (fat). Together, this adds up to diabetes.

“We were initially surprised to learn how much the pancreatic beta cell contributes to the onset and severity of diabetes,” said Jamey D. Marth, Ph.D., director of the Centre for Nanomedicine, who led the study.

“The observation that beta cell malfunction significantly contributes to multiple disease signs, including insulin resistance, was unexpected. We noted, however, that studies from other laboratories published over the past few decades had alluded to this possibility,” he added.

In healthy people, pancreatic beta cells monitor the bloodstream for glucose using glucose transporters anchored in their cellular membranes.

In this newly discovered pathway, high levels of fat were found to interfere with two key transcription factors—proteins that switch genes on and off.

The transcription factors are normally required for the production of an enzyme called GnT-4a that modifies proteins with a particular glycan (polysaccharide or sugar) structure.

Proper retention of glucose transporters in the cell membrane depends on this modification, but when the transcription factors aren’t working properly, GnT-4a”s function is greatly diminished.

So when the researchers fed otherwise normal mice a high-fat diet, they found that the animals’ beta cells could not sense and respond to blood glucose.

Preservation of GnT-4a function was able to block the onset of diabetes, even in obese animals.

The findings were published online August 14 in Nature Medicine.

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