Augmentation of RBP4/STRA6 signaling leads to insulin resistance and inflammation and the plausible therapeutic role of vildagliptin and metformin

A role of Retinol Binding Protein-4 (RBP4) in insulin resistance is widely studied. However, there is paucity of information on its receptor viz., Stimulated by Retinoic Acid-6 (STRA6) with insulin resistance. To address this, we investigated the regulation of RBP4/STRA6 expression in 3T3-L1 adipocytes exposed to glucolipotoxicity (GLT) and in visceral adipose tissue (VAT) from high fat diet (HFD) fed insulin-resistant rats. 3T3-L1 adipocytes were subjected to GLT and other experimental maneuvers with and without vildagliptin or metformin. Real-time PCR and western-blot experiments were performed to analyze RBP4, STRA6, PPARγ gene and protein expression. Adipored staining and glucose uptake assay were performed to evaluate lipid and glucose metabolism. Oral glucose tolerance test (OGTT) and Insulin Tolerance Test (ITT) were performed to determine the extent of insulin resistance in HFD fed male Wistar rats. Total serum RBP4 was measured by quantitative sandwich enzyme-linked immunosorbent assay kit. Adipocytes under GLT exhibited significantly increased RBP4/STRA6 expressions and decreased insulin sensitivity/glucose uptake. Vildagliptin and metformin not only restored the above but also decreased the expression of IL-6, NFκB, SOCS-3 along with lipid accumulation. Furthermore, HFD fed rats exhibited significantly increased serum levels of RBP4 along with VAT expression of RBP4, STRA6, PPARγ, IL-6. These molecules were significantly altered by the vildagliptin/ metformin treatment. We conclude that RBP4/STRA6 pathway is primarily involved in mediating inflammation and insulin resistance in adipocytes and visceral adipose tissues under glucolipotoxicity and in insulin resistant rats.

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Fabrication,characterization and application of laccase–nylon 6,6/Fe3+ composite nanofibrous membrane for 3,3′-dimethoxybenzidine detoxification

Bioprocess and Biosystems Engineering - In this study, laccase was immobilized on nylon 6,6/Fe3+ composite (NFC) nanofibrous membrane and used for the detoxification of...     

Uncovering Antimicrobial Peptide from Zophobas atratus Using Transcriptome Analysis

International Journal of Peptide Research and Therapeutics - Zophobas atratus which is also referred as giant meal worm, belongs to the largest darkling beetle family. The rich protein and fat...     

Supplementation of articular cartilage-derived chondroprogenitors with bone morphogenic protein-9 enhances chondrogenesis without affecting hypertrophy

Biotechnology Letters - Chondroprogenitors (CPCs) have emerged as a promising cellular therapy for cartilage-related pathologies due to their inherent primed chondrogenic potential. Studies report...     

Thiol Metabolism and Redox Regulation of Cellular Functions. Series I: Life and Behavioural Sciences

α,β-Unsaturated carbonyl compounds have been implicated in a number of environmentally-related diseases. Often, the presence of α,β-unsaturated carbonyl functionality as part of either an aliphatic or cyclic structure is considered a structural alert for cytotoxicity. We examined the cytotoxicity of methyl vinyl ketone (MVK), an aliphatic, straight-chain α,β-unsaturated carbonyl compound, in murine GT1-7 hypothalamic neurons. In addition to its widespread environmental occurrence, MVK was selected due to its extensive use in the chemical industry. Also, MVK is a close structural analog of hydroxymethylvinyl ketone that, in part, mediates the cytotoxic effects of 1,3-butadiene in vivo. It was found that MVK at low micromolar concentrations induced extensive cell death that retained key features of apoptosis such as chromatin condensation and DNA fragmentation. The MVK-induced apoptosis was associated with depletion of glutathione, disruption of mitochondrial transmembrane potential, and increased generation of reactive oxygen species (ROS). Supplementation of neuronal cells with Trolox offered partial, but significant, protection against the MVK-induced cytotoxicity, presumably due to scavenging of ROS in situ. The suggested sequence of events in the MVK-induced apoptosis in neuronal cells involves the depletion of cellular glutathione followed by an increased generation of ROS and finally the loss of mitochondrial function.     

Right atrial appendage tachycardia: A rare cause of tachycardia induced cardiomyopathy in a 4-year-old child

We present a rare case of tachycardiomyopathy in a 4-year-old girl. The child had incessant atrial tachycardia (AT) and refractory heart failure. Right atrial appendage (RAA) was localised as the source of the ectopic tachycardia. The child underwent successful radiofrequency ablation (RFA) using 3-D electroanatomical mapping. Fluoroscopy was used sparingly only to rule out underlying anomalies. The left ventricular functions returned to normal by one month after the procedure. RAA AT is rare in very young children and usually necessitates surgical appendectomies. RFA is a challenge in such age groups and there are very few published literature on RAA AT in very young children.