<p>Toll-like Receptors as a Potential Drug Target for Diabetes Mellitus and Diabetes-associated Complications</p>

Abstract

Diabetes mellitus (DM) is a chronic endocrine disease distinguished by hyperglycemia due to disturbance in carbohydrate or lipid metabolism or insulin function. To date, diabetes, and its complications, is established as a global cause of morbidity and mortality. The intended aim during the management of diabetes is to maintain blood glucose close to normal because the majority of patients have poor control of their elevated blood glucose and are highly prone to severe macrovascular and microvascular complications. To decrease the burden of the disease and its complications, scientists from various disciplines are working intensively to identify novel and promising drug targets for diabetes and its complications. Increased and ongoing investigations on mechanisms relating to diabetes and associated complications could potentially consider inflammatory cascades as a promising component of the strategy in the prevention and control of diabetes and its complications. The potential of targeting mediators of inflammation like toll-like receptors (TLRs) are part of current investigation by the scientific community. Hence, the aim of the present review is to discuss the role of TLRs as a potential drug target for diabetes and diabetes associated complications.

In vitroandin silicoanalysis proving DPP4 inhibition and diabetes associated gene network modulation by a polyherbal formulation –Nisakathakadi Kashaya

“…A cluster of 23 genes were identified as common among all diabetic complications and included markers such as TNF, TLR4, CCL2, SOD1, TGFβ and SOD2, all of which are deregulated and involved in various stages of diabetic pathogenesis (Huang et al, 2018; Yehualashet, 2020; Zhao et al, 2020; Tesch, 2008; Pickering et al, 2018).…”

“…The results of Venn analysis as observed (Fig-7A) showed that 37 proteins were common among all the diabetes associated diseases and diabetic complications. Proinflammatory markers like NFKB1 and TNFα, characteristic of the insulin resistance were present in the cluster along with lipid regulatory and obesity-linked PPARα and PPARγ [26-28] The other critical markers were insulin signalling molecules like AKT1 and PI3K, demonstrating that these core pathways involved in diabetic pathogenesis can be regulated by multitargeted action of NK [26]. One of the overlap categories in the Venn analysis is obesity, fatty liver and diabetic complications which has 27 shared proteins.…”

Toll like receptor 4 gene Asp299Gly polymorphism increases the risk of diabetic microvascular complications: a meta analysis

“…The activation of Nuclear factor-kappa B(NF-κB) was induced by regulating the dependent or independent signaling pathways of Myeloid differentiation factor 88(MyD88) [ 30 ]. TLR4/MyD88/NF-κB signaling pathway leads to the increase of downstream pro-inflammatory cytokines and adhesion molecules, participate in the occurrence of inflammatory reactions [ 31 ], and cause the pathological changes such as vascular extravasation or increased vascular permeability, vascular obstruction, and degeneration and pathological changes of neovascularization, thus leading to the occurrence and development of DMI [ 32 , 33 ]. Activation of the TLR4 signaling pathway mediates the inflammatory response, which is associated with TLR4 gene polymorphism [ 34 ].…”

Markers, pathways, and current evidence for periodontitis-associated insulin resistance: A narrative review

“…This impairs insulin secretion and insulin sensitivity in β-cells of pancreatic islets and peripheral tissues, respectively [ Table 1 ]. [ 14 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 ]…”