Diabetes culprit may be a single enzyme

The enzyme in question–called 12-LO–plays a key role in promoting oxidative stress brought on by obesity in the pancreatic cells, according to a new study that appears ahead of print in the journal Molecular and Cellular Biology.

“We surmised that when individuals eat high-fat foods and become overweight, the beta cells of their pancreases fail to produce sufficient insulin,” principal investigator Raghavendra Mirmira said in a statement.  In previous studies, Mirmira and his colleagues, along with collaborators at Eastern Virginia Medical School, found that 12-LO only exists in the pancreas cells of people who become overweight.

To test the theory that 12-LO is connected to diabetes, investigators at the Indiana University School of Medicine genetically engineered mice that lacked the gene for 12-LO only in their pancreas cells.  Both control mice and knockout mice were divided into two groups each and fed a low-fat or high-fat diet.  In the high-fat diet group, both the control mice and those lacking 12-LO developed obesity and insulin resistance.  When examining the pancreatic beta cells in the mice, researchers found that the beta cells in the knockout mice were intact and healthy, while those from the control mice showed oxidative damage.  This suggests that 12-LO and the resulting HETEs, or hydroxyeicosatetraenoic acid, caused the beta cell failure in the control mice.  HETEs are harmful to the mitochondria, which then cannot generate enough energy to spur insulin production in the pancreatic cells.

REFERENCE:  Fierce BioTech Research; 19 AUG 2014; Emily Mullin

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