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Nobel Prize Winner Proposes New Theory for Cause of Type 2 Diabetes

Evidence points to lack of biological oxidants (February 28)

At 85, Nobel laureate James D. Watson, the co-discoverer of the double-helix structure of DNA, continues to advance intriguing scientific ideas. His latest, a hypothesis on the causation of type 2 diabetes, appeared online February 28 in The Lancet and will be published in that journal’s March 1 issue.

Watson’s hypothesis suggests that diabetes, dementias, cardiovascular disease, and some cancers are linked to a failure to generate sufficient biological oxidants, called reactive oxygen species (ROS). Watson also argues the case for a better understanding of the role of exercise in helping to remedy this deficiency.

“The prevalent view of type 2 diabetes,” Watson says, “is that an excess of intracellular oxidation causes inflammation, which in turn kills cells in pancreatic tissue.” Proper function of those cells, it is well understood, is critical for the maintenance of normal blood glucose levels.

Over the last several years, Watson has been puzzling out an alternative view. He does not question that pancreatic tissue in people with type 2 diabetes is inflamed — but he does present a novel theory of why. “The fundamental cause, I suggest, is a lack of biological oxidants, not an excess,” he says.

The body’s cells cannot survive without making both oxidants and antioxidants. “There is a delicate balance” between the two, Watson observes. Physical exercise prompts the body to make large numbers of oxidants (ROS molecules). In the endoplasmic reticulum (ER) of cells, one such “species,” the oxidant hydrogen peroxide (H2O2), helps forge disulfide bonds that stabilize proteins as they fold.

When there is not enough oxidation in the ER, Watson says, proteins emerge unfolded and cannot function. This, he proposes, causes the inflammation that harms the pancreas, sometimes causing type 2 diabetes. Hence, Watson suggests, exercise, which promotes oxidation, may have a beneficial effect on individuals with high blood sugar.

Sources: Cold Spring Harbor Laboratory; February 27, 2014.

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