The Role of Toll-Like Receptors in Diabetes-Induced Inflammation: Implications for Vascular Complications.
Diabetes confers an increased risk for both microvascular and macrovascular complications. Numerous studies have reported increased levels of biomarkers of inflammation that could predispose to vascular complications. The pattern recognition receptors of the innate immune response, such as Toll-like receptors (TLRs), especially TLR2 and TLR4, have been incriminated in both atherosclerosis and insulin resistance. Studies have reported increased expression and activity of these receptors in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus. Most recently, knockout of TLR2 has been shown to attenuate the proinflammatory state of T1DM and the progression of diabetic nephropathy. The increased activity of TLRs in diabetes could be the result of a conspiracy of both endogenous and exogenous ligands. Biomediators of increased TLR2 and TLR4 activity include tumor necrosis factor-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1, and type 1 interferons. Modulating these TLRs could be beneficial in forestalling diabetic complications given the pivotal role of inflammation in both microvascular and macrovascular complications.
Laboratory of Atherosclerosis and Metabolic Research, UC Davis Medical Center, Sacramento, CA, 95817, USA, ijialal@ucdavis.edu.
Ishwarlal
I
Jialal
Harmeet
H
Kaur