Single enzyme triggers diabetes, says study

A single enzyme promotes the obesity-induced oxidative stress in the pancreatic cells that leads to pre-diabetes and diabetes, researchers have discovered. The drugs that can interfere with this enzyme can prevent or even reversing diabetes.

The enzymatic action by 12-lipoxygenase (12-LO) is the last step in the production of certain small molecules that harm the cell.

"Our research is the first to show that 12-LO in the beta cell is the culprit in the development of pre-diabetes, following high fat diets," said principal investigator Raghavendra Mirmira from Indiana University's school of medicine, Indianapolis.

For the study, researchers genetically engineered mice that lacked the gene for 12-LO exclusively in their pancreas cells.

Mice were either fed a low-fat or high-fat diet.

Both the control mice and the knockout mice on the high fat diet developed obesity and insulin resistance.

The investigators also examined the pancreatic beta cells of both knockout and control mice.

Those from the knockout mice were intact and healthy while those from the control mice showed oxidative damage, demonstrating that 12-LO and the resulting hydroxyeicosatetraenoic acid (HETEs) caused the beta cell failure.

HETEs harm the mitochondria, which then fail to produce sufficient energy to enable the pancreatic cells to manufacture the necessary quantities of insulin.

The fatty diet used in the study comprised mostly saturated (bad) fats.

According to Mirmira, the unsaturated and mono-unsaturated fats are unlikely to have the same effects.

The research was published online in the journal Molecular and Cellular Biology.