Differential effect of insulin treatment on decreased levels of beta-defensins and Toll-like receptors in diabetic rats

Many infections are associated with diabetes, as the ability of the body to fight pathogens is impaired. Recently, altered levels of defensins and polymorphism in Toll-like receptors (TLRs), two crucial components of the innate immune system, have been associated with diabetes. To study the functionality of the innate immune system during diabetes, we measured the expression levels of rat beta-defensin I (rBD-1), rBD-2, rTLR2, and rTLR4 in the kidney, lung, liver, and brain of streptozotocin-induced diabetic rats with and without insulin treatment. In the kidneys of diabetic rats, lower levels of rBD-1, rTLR2, and rTLR4 were found. These low levels could be restored with insulin treatment. In contrast, rBD-2 was highly induced in the lungs of diabetic rats, most likely, as a result of a pro-inflammatory response. In the liver and brain of diabetic rats, lower levels of TLRs and/or defensins could not be restored with insulin treatment. Our findings suggest for the first time that high blood glucose and/or insulin deficiency abrogates the expression level of the innate immune system components, defensins and TLRs, explaining the recurrent infections during diabetes. These findings may lay the grounds for future design of novel treatments that will induce defensins and TLRs and, as a result, bolster the immune system in diabetic patients. (c) 2006 Elsevier Ltd. All rights reserved.