<p>Thioredoxin-Interacting Protein as a Novel Potential Therapeutic Target in Diabetes Mellitus and Its Underlying Complications</p>

Abstract

Diabetes mellitus (DM) is a common metabolic disorder which is characterized by a persistent increment of blood glucose. Globally, DM affects millions of people and the prevalence is increasing alarmingly. The critical step in the pathophysiology of DM is the loss of βcells of the pancreas, which are responsible for the secretion of insulin. Thioredoxin-interacting protein (TXNIP) is among the factors that control the production and loss of the pancreatic βcells. TXNIP is an α-arrestin that can bind and inhibit thioredoxin (the antioxidant protein) which is produced in the pancreatic islet after glucose intake. Numerous studies illustrated that elevated TXNIP levels were found to induce β-cell apoptosis; whereas TXNIP deficiency protects against type I and type II diabetes by promoting β-cell survival. Nowadays, TXNIP depletion is becoming a key factor in pancreatic β-cell survival enhancement. In the present review, targeting TXNIP is found to be relevant as a unique therapeutic opportunity, not only to improve insulin secretion and sensitivity, but also ameliorating the long term microvascular and macrovascular complications of the disease. Thus, TXNIP inhibitors that could reduce the expression and/or activity of TXNIP to non-diabetic levels are promising agents to halt the alarming rate of diabetes and its related complications.

TXNIP/TBP-2: A Master Regulator for Glucose Homeostasis

“…Tissue specific physiological role of TXNIP give us a lesson to learn the targeting tissues for each specific condition in diabetes ( Table 1 ). The specificity of TXNIP inhibition should be also considered since none of the known TXNIP modulators target only TXNIP, rather broadly affecting transcriptome [ 154 ]. In addition, although drug treatments such as insulin, glucagon-like peptide-1 (GLP-1/Exendin-4), thiazolidinediones (TZD), dipeptidyl peptidase 4 (DPP-IV) inhibitors, sodium–glucose co-transporter-2 (SGLT2) inhibitors, and metformin are successful to provide the therapeutics in T1D or T2D [ 155 , 156 , 157 , 158 , 159 ], none of these therapeutics provide a “functional cure” for the diabetes, which means life-long drug treatment to ameliorate diabetes is required for the patients.…”

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

“…2 Diabetes mellitus is a common public health threat affecting millions of people in the world of all ages, gender, race and ethnic groups. 3 The burden of DM is increasing throughout the world, and around 80% of diabetes deaths occur mainly in low and middle-income countries. 4 Based on the pathogenesis of hyperglycemia, most patients with DM are either Type 1 (insulin dependent) or Type 2 (non-insulin dependent).…”

“…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. 21 Hence, the present review is used to assess the role of Adipsin as a novel diagnostic parameter and its implication in T2DM.…”

Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases

“…Many studies of TXNIP cellular expression in peripheral cells have focused on pancreatic islet cells in terms of effects on glucose uptake and metabolism, insulin secretion, and cell death. These studies have been extensively reviewed for their significance in understanding mechanisms of diabetes (for recent reviews, see [ 69 , 70 ]). For this review focusing on brain diseases with inflammatory components, we will consider TXNIP expression in macrophages and its consequences on inflammation.…”