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.

Graphic abstract

     

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.     

Design,Synthesis, and Structure–Activity Relationships of Novel 1-(Substituted)-2-Methyl-3-(4-Oxo-2-Methylquinazolin-3(4H)-yl) Isothioureas for Their Anti-HIV and Antibacterial Activities

Russian Journal of Bioorganic Chemistry - In this study, a novel quinazolinone analogue was designed and synthesized by substituting the thiourea group and phenyl ring at N-3 and C-2 positions of...     

CULTURE AND BIOCHEMICAL ANALYSIS OF A TEA ALGAL PATHOGEN,CEPHALEUROS PARASITICUS1

To assess the current situation regarding the incidence of red rust disease in tea plants, an extensive survey was conducted in southern Indian tea plantations covering different tea cultivars and agroclimatic zones. The results indicated that the incidence of disease was more severe in tea seedlings than clones in all the agroclimatic zones. On the other hand, a simple, reliable, and reproducible technique was standardized for culturing Cephaleuros parasiticus G. Karst. isolated from infected tea leaves. Ten isolates were obtained, of which two were screened based on growth rate and culture characters for further studies. Ten culture media were tested for the culturing of C. parasiticus in which Trebouxia and Bristol media were the best followed by George, Go algal, and tea leaf extract media. Variations between isolates (Valparai C. parasiticus field number 27 [VCP27], Munnar C. parasiticus field number 11 [MCP11], and University of Texas culture number 2412 [UTEX2412]) of C. parasiticus were studied based on the growth pattern, protein expression profile, and cellular constituents in the filaments. The quantitative estimation of cellular constituents showed that there was no significant difference in these constituents among isolates. The detection of amino acids in the filaments of C. parasiticus isolates showed 16 free forms and 11 bound forms. Amino acids in bound form were higher in all the isolates than in free form of amino acids. The three isolates of C. parasiticus were closely related, with bands lying between the molecular weight of 116 and 35 kDa.     

Anti-HIV and Antibacterial Activities of Novel 2-(3-Substituted-4-oxo-3,4-dihydroquinazolin-2-yl)-2,3-dihydrophthalazine-1,4-diones

Russian Journal of Bioorganic Chemistry - In the present study, we have synthesized a series of novel 2-(3-substituted-4-oxo-3,4-dihydroquinazolin-2-yl)-2,3-dihydrophthalazine-1,4-diones by the...     

Discovery of new potential triplet acting inhibitor for Alzheimer’s disease via X-ray crystallography,molecular docking and molecular dynamics

Abstract

The most common brain disorder of late life is Alzheimer’s disease (AD), which is highly complicating dementia. There are several drug targets which are reported to control the severe level of AD; notably, acetylcholinesterase, β-Secretase and glycogen synthase kinase enzymes are approached as a good drug targets for AD. Hence, the present study mainly focused to discover newly synthesized molecule (7-propyl-6H-pyrano[3,2-c:5,6-c']dichromene-6,8(7H)-dione) as a potential triplet acting drug for above said enzymes through the analysis of X-ray crystallography, molecular docking, molecular dynamics and quantum chemical calculation. The target drug molecule was crystallized in the monoclinic crystal structure with P21/n space group. The structure was solved by SHELXS and refined by SHELXL. The crystal packing is stabilized by C???H···O type of interactions. Further, the induced fit docking shows that the molecule has high docking score, glide energy, favorable hydrogen bonding and hydrophobic interactions on the protein targets. The molecular dynamics simulation was performed to understand the stability of the molecule in the presence of active site environment. Finally, quantum chemical calculation has been carried out for the molecule in gas phase and for the corresponding molecule lifted from the active site region. The structural comparison between gas phase and active site helps to understand the conformational modification of the molecule in the active site.

Communicated by Ramaswamy H. Sarma