Modulation of toll-like receptors by insulin.

Toll-like receptors (TLRs) are first-line molecules for initiating the innate immune responses and mediating functional activation in immune effector cells. A family of 10 functional human TLRs altogether can recognize the ligands that do not exist in the host and initiate the inflammatory cascades. This triggers the production of inflammatory cytokines, chemokines, and interferons. Overactivation of innate immunity might lead to immune-mediated inflammatory disorders. Besides that, TLRs are currently viewed as active participants in the cross-communication between immunity and metabolic health. Recent data directly implicate the activation of inflammatory pathways in the pathogenesis of type 1 and type 2 diabetes, atherosclerosis, obesity, and also cancer. The following approaches to develop new TLR drugs have been undertaken: generating TLR agonists/antagonists, creating monoclonal antibody to TLRs, blocking the key molecules in the signaling pathways, down-modulating TLR signaling. In this article, we briefly review the involvement of TLRs in diseases associated with metabolic alterations, underscoring the modulation of TLRs by insulin. (C) 2011 Lippincott Williams & Wilkins, Inc.