Netrin as a Novel Biomarker and Its Therapeutic Implications in Diabetes Mellitus and Diabetes-Associated Complications

Abstract

Diabetes is a multifactorial metabolic syndrome and is one of the shared long-lasting illnesses globally. It is linked to long-term microvascular and macrovascular complications that contribute to disability, compromised quality of life, and reduction in lifespan, which eventually leads to death. This disease is not only incurring significant economic burden but also adversely affects the patients, caregivers, communities, and the society at large. The interruption of diabetes progress and its complications is a primary focus of scientific communities. In spite of various diagnostic modalities for diabetes, there is a limited marker to investigate the risk and progress of its complications. Netrin has recently received more attention as a biomarker of diabetes and a broader range of long-term complication. Therefore, the impetus of this review is to exhaustively discuss the role of Netrin as a potential biomarker and its therapeutic implication in diabetes and diverse sets of microvascular and macrovascular complications of diabetes. It also discourses the possible mechanisms of Netrin for the said pharmacological effect for a better understanding of the development and progression of diabetes and its complications in relation to this protein. It enables protective measures to be applied at the subclinical stage and the responses to preventive or therapeutic measures to be scrutinized. Besides, it might also facilitate the appraisal of novel therapeutic options for diabetes and various complications through modifying the endogenous Netrin and provide surrogate endpoints for intervention.

Potential Effect of Hydroxychloroquine in Diabetes Mellitus: A Systematic Review on Preclinical and Clinical Trial Studies

“…Type II diabetic patients might require insulin in addition to oral hypoglycemic agents, which is consistently augmented the side effects [7]. In addition, population-wide lifestyle modification, along with early diagnosis and cost-effective treatment of DM, is required to save lives and/or prevent devastating diabetesrelated complications [2,8].…”

<p>Plasma Adipsin as a Biomarker and Its Implication in Type 2 Diabetes Mellitus</p>

“…16,17 However, these diagnostic tools are associated with reduced sensitivity and/or specificity to detect diabetes in its early stage. 18 To overcome such problems different newer diagnostic methods were developed by targeting endogenous proteins such as Leptin, TNF-alpha, C-reactive protein (CRP), 19 Netrin, 20 Thioredoxin-interacting protein (TXNIP). 3 But, these novel methods have been also associated with increased cost.…”

<p>Targeting Netrin-1 and -4 as a Novel Diagnostic Parameter and Treatment Option for Diabetic Retinopathy</p>

“…30,31 Among them, Netrin was studied by various experimental and clinical models. 7,19,24,32,33 The level of Netrin protein in the plasma has been positively correlated with DR. As compared with the normal controls, the level of Netrin was markedly increased in the early phase of DR. As shown in Table 1, different experimental studies revealed that the level of Netrin in the cornea increased substantially at the early phase of DR ( Table 1).…”

“…2 Due to that protein mostly found in nerve endings were used as indicators for changes which occurred in the system. 7 Among them, Netrin has been recently considered as a novel biomarker and therapeutic agent for DR. Netrin-1…”

“…3,6 DR is characterized by specific loss of pericytes, which leads to an augmented blood vessel permeability, and the development of new blood vessels (retinal neovascularization). 7 In addition, stiffening of the membrane in the eye and apoptosis of endothelial cells are detected during the pathogenesis, which collectively contributes to the damage of the blood-retinal barrier. Moreover, marked loss of endothelial cells and pericytes leads to upregulation of vascular endothelial growth factor (VEGF) by activating hypoxia-inducible factor 1 (HIF-1).…”