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Chronic Exposure to Superantigen May Influence T2DM Risk

Chronic exposure to superantigens, such as Staphylococcus aureus, may play a role in impaired glucose metabolism and the development of type 2 diabetes in the overweight and obese.

Chronic exposure to superantigens, such as Staphylococcus aureus, may play a role in impaired glucose metabolism and in the development of type 2 diabetes in the overweight and obese, according to the results of a study in rabbits published recently.

According to researchers led by Bao G. Vu, of the department of microbiology at the University of Iowa, “this outcome can be traced back to the ability of superantigens to cause insulin resistance through inducing chronic systemic inflammation and lipolysis.”

Previous research has shown that S. aureus is associated with life-threatening infections in humans, including toxic shock syndrome and pneumonia, among others. Researchers have hypothesized that the presence of S. aureus may also be associated with the development of type 2 diabetes among obese individuals. In previous work, Vu and colleagues showed that S. aureus toxic shock syndrome toxin -1 (TSST-1) was associated with proinflammatory cytokines.

To explore this association between TSST-1 and diabetes further, Vu and colleagues challenged rabbits with a sublethal dose of TSST-1 or saline for 6 weeks and then monitored glucose metabolism weekly. After the 6-week period, the pancreas was extracted and tissue samples from three areas were selected for RNA extraction.

Those rabbits administered TSST-1 were found to have gradually reduced ability to metabolize glucose compared with the control group of rabbits. The difference in metabolism was not present until after the first 2 weeks of TSST-1 administration.

The researchers also found that although there was no difference in weight between the two groups of rabbits, animals administered TSST-1 had higher levels of tumor necrosis factor-alpha (TNF-α) and endotoxin levels in the circulation, indications of chronic inflammation in vivo.

“Prolonged exposure of rabbits to TSST-1 induced chronic inflammation, elevated the endotoxin levels in the circulation, and impaired glucose tolerance, all of which are conditions seen in [type 2 diabetes] patients,” the researchers wrote.

Next, Vu and colleagues looked at the influence of TSST-1 on adipocytes in vivo and found that rabbits exposed to TSST-1 had significantly upregulated levels of interleukin (IL)-6, IL-8, TNF-α, and monocyte chemoattractant protein-1 transcript levels when compared with control rabbits.  

“Collectively, TSST-1 induced proinflammatory signal (IL-6, IL-8, and TNF-α) production in adipocytes, which could contribute directly to the development and maintenance of the chronic systemic inflammation observed in rabbits,” the researchers wrote.

Finally, the researchers explored whether chronic exposure to TSST-1 was associated with insulin resistance. They tested whether adipocytes could take up glucose after exposure to TSST-1 and found that after 6 weeks exposure, the rabbits absorbed significantly less 2-deoxy-D-glucose than those rabbits in the control group.


Reference: Vu BG, et al. Chronic superantigen exposure induces systemic inflammation elevated bloodstream endotoxin, and abnormal glucose tolerance in rabbits: possible role in diabetes. mBio 2015:6(2):e02554-14.