High Blood Sugar Can Trigger Infections in Diabetes

Researchers have discovered that molecular mechanism could produce dangerous infections in the feet and hands of patients with uncontrolled diabetes.

A team of investigators from Case Western Reserve University revealed how 2 dicarbonyls—methylglyoxal (MGO) and glyoxal (GO) change the structure of human beta-defensn 2 (hBD-2) peptides, which hinder the peptides’ ability to fend off infection as well as inflammation.

The authors collaborated on a series of experiments that compared the mass spectra, the potential for killing bacteria, and the immune cell-attracting ability of dicarbonyl-treated hBD-2 with untreated hBD-2. This beta-defensin, they note, was initially exposed to the activities of MGO and GO, both of which increase in individuals with high blood sugar. Mass spectral analysis demonstrated that MGO was the more reactive of the dicarbonyls, and bacteria-killing and chemotactic experiments were subsequently performed by exposing hBD-2 to MGO.
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The researchers compared the mass spectra for the dicarbonyl-exposed hBD-2 with untreated hBD-2. In the dicarbonyl-exposed hBD-2, the team found the dicarbonyl irreversibly binds to 2 positively charged arginine amino acids located near the surface of the hBD-2 peptide, in addition to binding to several other amino acid residues. They also compared dicarbonyl-treated hBD-2 to untreated hBD-2, in terms of their ability to kill gram-negative bacteria, finding that untreated hBD-2 is effective at killing the bacteria, while dicarbonyl-exposed hBD-2 hampered this defensin’s ability to defend against bacteria.

“It would be premature to suggest that our findings can influence or be directly incorporated into the treatment protocol used by the primary care physician in the treatment of soft tissue infections, including those of the hand and foot in diabetic patients,” says study co-author Wesley Williams, PhD, of the department of biological sciences at Case Western Reserve University School of Dental Medicine.

While the study results show “a dramatic loss in antimicrobial peptide function with respect to the beta-defensin family of peptides, it must be remembered that our findings have not been demonstrated in animals or patients,” says Williams, noting that the molecular mechanism described in this research has been “well-characterized in some other proteins.”

Thus, “our findings illustrate the ubiquitous role that hyperglycemia plays in the clinical presentation of diabetic pathologies,” he says. “Physicians are well aware of the dangers of high blood sugar to human health. Our findings simply notify the physician that difficulty in infection control may not simply be due to vascular issues, but perhaps also to the direct effect of hyperglycemia on the function of specific components of the immune system.”

—Mark McGraw

Reference

Kiselar J, Wang X, et al. Modification of β-Defensin-2 by Dicarbonyls Methylglyoxal and Glyoxal Inhibits Antibacterial and Chemotactic Function In Vitro. PLOS ONE. 2015.