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Renal gluconeogenesis in insulin resistance:A culprit for hyperglycemia in diabetes

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World Journal of Diabetes 2021年第5期12卷 556-568页

作者： Rajni Sharma swasti Tiwari Department of Molecular Medicine and Biotechnology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknow 226014India

Renal gluconeogenesis is one of the major pathways for endogenous glucose *** in this process may contribute to hyperglycemia in cases with insulin resistance and *** reviewed pertinent studies to elucidate the role of renal gluconeogenesis regulation in insulin resistance and diabetes.A consensus on the suppressive effect of insulin on kidney gluconeogenesis has started to build ***-resistant models exhibit reduced insulin receptor(IR)expression and/or post-receptor signaling in their kidney *** IR expression or post-receptor signaling can cause impairment in insulin’s action on kidneys,which may increase renal gluconeogenesis in the state of insulin *** is now established that the kidney contributes up to 20%of all glucose production via gluconeogenesis in the post-absorptive ***,the rate of renal glucose release excessively increases in *** rise in renal glucose release in diabetes may contribute to fasting hyperglycemia and increased postprandial glucose *** glucose release by the kidneys and renal expression of the gluconeogenic-enzyme in diabetic rodents and humans further point towards the significance of renal ***,the available literature suggests that impairment in renal gluconeogenesis in an insulinresistant state may contribute to hyperglycemia in type 2 diabetes.

关键词： Renal gluconeogenesis Insulin-resistance Insulin Insulin receptor signaling Diabetes Gluconeogenic enzymes

Role of Contact and Contact Modification on Photo-response in a Charge Transfer Complex Single Nanowire Device

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Nano-Micro Letters 2014年第1期6卷 63-69页

作者： Rabaya Basori A.K.raychaudhuri Theme Unit of Excellence in Nano Device Technology and Department of Condensed Matter Physics and Materials Science S.N. Bose National Centre for Basic Sciences

We investigated the feasibility of obtaining large photoresponse in metal-semiconductor-metal(MSM) type single nanowire device where one contact can be blocking type. We showed that suitable modification of the blocking contact by deposition of a capping metal using focused electron beam(FEB) can lead to considerable enhancement of the photoresponse. The work was done in a single Cu:TCNQ nanowire device fabricated by direct growth of nanowires(NW) from pre-patterned Cu electrode which makes the contact ohmic with the other contact made from Au. Analysis of the data shows that the large photoresponse of the devices arises predominantly due to reduction of the barriers at the Au/NW blocking contact on illumination. This is caused by the diffusion of the photo generated carriers from the nanowires to the contact region. When the barrier height is further reduced by treating the contact with FEB deposited Pt, this results in a large enhancement in the device photoresponse.

关键词： Nanowire Cu:TCNQ MSM device FEB deposition Photo-response

Monte Carlo study of B-cell receptor clustering mediated by antigen crosslinking and directed transport

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Cellular & Molecular Immunology 2011年第3期8卷 255-264页

作者： A Srinivas Reddy Philippos K Tsourkas Subhadip raychaudhuri Department of Biomedical Engineering University of California DavisDavisUSA Biophysics Graduate Group University of California DavisDavisUSA Graduate Group in Applied Mathematics University of California DavisDavisUSA

It is known from experiments that in the presence of soluble antigen,B-cell receptors(BCRs)assemble into microclusters and then collect into a macrocluster known as a‘cap’.However,the mechanisms of BCR cluster formation during recognition of soluble antigens remain *** previous work,we demonstrated that effective intrinsic attractions among BCRs can lead to the formation of small microclusters of BCR *** effective intrinsic attractions could be caused by multivalent antigen binding,association with lipid rafts,or other biochemical *** the present study,we have developed and studied a Monte Carlo model of BCR clustering mediated by explicit binding and crosslinking of soluble bivalent *** crosslinking is shown to microcluster BCRs in an affinity-dependent manner and also in a biologically relevant timescale;however,antigen crosslinking alone does not appear to be sufficient for the formation of a single macrocluster of receptor *** show that directed transport of BCRs is needed to drive the formation of large *** constructed a simple model of directed transport,where BCR molecules diffuse towards the largest cluster or towards a random BCR microcluster,which results in a single macrocluster of receptor *** mechanisms for both types of directed transport are compared using network-based *** also develop and use appropriate network measures to analyze the effect of BCR and antigen concentration on BCR clustering,the stability of the formed clusters over time and the size of BCR–antigen crosslinked chains.

关键词： B-cell activation B-cell receptor cell signaling Monte Carlo simulation receptor clustering

Liver or kidney:Who has the oar in the gluconeogenesis boat and when?

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World Journal of Diabetes 2023年第7期14卷 1049-1056页

作者： Biswajit Sahoo Medha Srivastava Arpit Katiyar Carolyn Ecelbarger swasti Tiwari Department of Molecular Medicine and Biotechnology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknow 226014India Department of Medicine Georgetown UniversityWashingtonDC 20057United States

Gluconeogenesis is an endogenous process of glucose production from noncarbohydrate carbon *** the liver and kidneys express the key enzymes necessary for endogenous glucose production and its export into *** would be remiss to add that more recently gluconeogenesis has been described in the small intestine,especially under high-protein,lowcarbohydrate *** contribution of the liver glucose release,the net glucose flux,towards systemic glucose is already well *** liver is,in most instances,the primary bulk contributor due to the sheer size of the organ(on average,over 1 kg).The contribution of the kidney(at just over 100 g each)to endogenous glucose production is often under-appreciated,especially on a weight *** is released from the liver through the process of glycogenolysis and *** glucose release is almost exclusively due to gluconeogenesis,which occurs in only a fraction of the cells in that organ(proximal tubule cells).Thus,the efficiency of glucose production from other carbon sources may be superior in the kidney relative to the liver or at least on the *** both these tissues,gluconeogenesis regulation is under tight hormonal control and depends on the availability of *** and renal gluconeogenesis are differentially regulated under various pathological *** impact of one source vs the other changes,based on post-prandial state,acid-base balance,hormonal status,and other less understood *** organ has the oar(is more influential)in driving systemic glucose homeostasis is still inconclusive and likely changes with the daily rhythms of *** reviewed the literature on the differences in gluconeogenesis regulation between the kidneys and the liver to gain an insight into who drives the systemic glucose levels under various physiological and pathological conditions.

关键词： Gluconeogenesis in the kidney and liver Diabetes Hormonal regulation Metabolic acidosis Insulin resistance Net glucose metabolism

Insulin receptors in the kidneys in health and disease

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World Journal of Nephrology 2019年第1期8卷 11-22页

作者： Sarojini Singh Rajni Sharma Manju Kumari swasti Tiwari Department of Molecular Medicine and Biotechnology Sanjay Gandhi Postgraduate Institute of Medical Sciences

Insulin is an important hormone that affects various metabolic processes,including kidney *** in insulin's action leads to insulin resistance in the target *** defects in post-receptor insulin signaling,impairment at the receptor level could significantly affect insulin sensitivity of the target *** kidney is a known target of insulin;however,whether the kidney develops "insulin resistance" is *** of the insulin receptor(IR) expression and its function is very well studied in major metabolic tissues like liver,skeletal muscles,and adipose *** physiological relevance of IRs in the kidney has recently begun to be *** credit goes to studies that showed a wide distribution of IR throughout the nephron segments and their reduced expression in the insulin resistance ***,altered renal and systemic metabolism observed in mice with targeted deletion of the IR from various epithelial cells of the kidney has strengthened this *** this review,we recapitulate the crucial findings from literature that have expanded our knowledge regarding the significance of the renal IR in normal-and insulin-resistance states.

关键词： Insulin receptor Insulin resistance Kidney disease Renal sodium reabsorption Gluconeogenesis Proteinuria Systemic blood pressure

Reference gene panel for urinary exosome-based molecular diagnostics in patients with kidney disease

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World Journal of Nephrology 2024年第3期13卷 62-72页

作者： Deendayal D Mishra Pramod K Maurya swasti Tiwari Department of Molecular Medicine and Biotechnology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknow 226014Uttar PradeshIndia

BACKGROUND Kidney disease is a severe complication of diabetes that often leads to end-stage renal *** diagnosis is crucial for prevention or ***,the current diagnostic methods,with their limitations in detecting the disease in its early stages,underscore the urgency and importance of finding new *** encapsulated inside urinary exosomes(UEs)have potential as early biomarkers for kidney *** need for reference miRNAs for accurate interpretation currently limits their translational *** To identify consistently expressing reference miRNAs from UEs of controls and patients with type 2 diabetesmellitus(T2DM)and biopsy-confirmed kidney *** miRNA profiling was performed on UEs from 31 human urine samples using a rigorous and unbiased *** UEs were isolated from urine samples collected from healthy individuals(n=6),patients with T2DM(n=13),and T2DM patients who also had kidney diseases(including diabetic nephropathy,n=5;membranous nephropathy,n=5;and IgA nephropathy,n=2)through differential *** characterizing the UEs,miRNA expression profiling using microarray technology was *** Microarray data analysis identified 14 miRNAs that were consistently expressed in UEs from 31 human samples,representing various kidney conditions:diabetic controls,diabetic nephropathy,membrane nephropathy,IgA nephropathy,and healthy *** in silico analysis,we determined that 10 of these miRNAs had significant potential to serve as reference genes in *** We identified uniformly expressing UE miRNAs that could serve as reference genes kidney disease biomarkers.

关键词： miRNA Microarray Urinary exosomes Diabetic nephropathy Type 2 diabetes mellitus Kidney disease

Discrimination of membrane antigen affinity by B cells requires dominance of kinetic proofreading over serial engagement

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Cellular & Molecular Immunology 2012年第1期9卷 62-74页

作者： Philippos K Tsourkas Wanli Liu Somkanya C Das Susan K Pierce Subhadip raychaudhuri Department of Biomedical Engineering University of CaliforniaDavisCAUSA Laboratory of Immunogenetics National Institute of Allergy and Infectious DiseasesNational Institutes of HealthRockvilleMDUSA

B-cell receptor signaling in response to membrane-bound antigen increases with antigen affinity,a process known as affinity *** use computational modeling to show that B-cell affinity discrimination requires that kinetic proofreading predominate over serial *** find that if B-cell receptors become signaling-capable immediately upon antigen binding,which results in decreasing serial engagement as affinity increases,then increasing affinity can lead to weaker ***,antigen must stay bound to B-cell receptors for a threshold time of several seconds before becoming signaling-capable,a process similar to kinetic *** process overcomes the loss in serial engagement due to increasing antigen affinity,and replicates the monotonic increase in B-cell signaling with increasing affinity that has been observed in B-cell activation *** finding matches well with the experimentally observed time(,20 s)required for the B-cell receptor signaling domains to undergo antigen and lipid raft-mediated conformational changes that lead to Src-family kinase *** hypothesize that the physical basis for a threshold time of antigen binding might lie in the formation timescale of B-cell receptor *** time required for dimer formation decreases with increasing antigen affinity,thereby resulting in shorter threshold antigen binding times as affinity *** an affinity-dependent kinetic proofreading requirement results in affinity discrimination very similar to that observed in biological experiments.B-cell affinity discrimination is critical to the process of affinity maturation and the production of high-affinity antibodies,and thus our results have important implications in applications such as vaccine design.

关键词： computational modeling Monte Carlo lymphocyte signaling Lyn Syk

Kinetic Monte Carlo Study of the Type 1/Type 2 Choice in Apoptosis Elucidates Selective Killing of Cancer Cells under Death Ligand Induction

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Open Journal of Apoptosis 2015年第1期4卷 22-39页

作者： Subhadip raychaudhuri Department of Computational Biology Indraprastha Institute of Information Technology-Delhi New Delhi India

Death ligand mediated apoptotic activation is a mode of cell death that is widely used in cellular and physiological situations. Interest in studying death ligand induced apoptosis has increased due to the promising role of recombinant soluble forms of death ligands (mainly recombinant TRAIL) in anti-cancer therapy. A clear elucidation of how death ligands activate the type 1 and type 2 apoptotic pathways in healthy and cancer cells may help develop better chemotherapeutic strategies. In this work, we use kinetic Monte Carlo simulations to address the problem of type 1/ type 2 choice in death ligand mediated apoptosis of cancer cells. Our study provides insights into the activation of membrane proximal death module that results from complex interplay between death and decoy receptors. Relative abundance of death and decoy receptors was shown to be a key parameter for activation of the initiator caspases in the membrane module. Increased concentration of death ligands frequently increased the type 1 activation fraction in cancer cells, and, in certain cases changed the signaling phenotype from type 2 to type 1. Results of this study also indicate that inherent differences between cancer and healthy cells, such as in the membrane module, may allow robust activation of cancer cell apoptosis by death ligand induction. At the same time, large cell-to-cell variability through the type 2 pathway was shown to provide protection for healthy cells. Such elucidation of selective activation of apoptosis in cancer cells addresses a key question in cancer biology and cancer therapy.

关键词： Death Receptor Decoy Receptor Cell-to-Cell Variability TRAIL FasL

Cellotape Birefringent Filter: Some New Demonstrations

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Optics and Photonics Journal 2016年第7期6卷 139-145页

作者： Ayantika Khanra Barun raychaudhuri Department of Physics Presidency University Kolkata India

An easy method is put forward to estimate the optical bandwidth and the wavelength of maximum transmission of Lyot optical filter by measuring the change in phase retardation of birefringent plates as function of thickness. The objective is to demonstrate the experiment with common undergraduate laboratory equipment and thereby provide with an educational aid. The filter is fabricated with cellotape using its birefringence property. The accuracy of measurement is cross-checked with precision spectroradiometric measurements. Some simplification is suggested in the theoretical derivation of the transmitted intensity and a possibility of realizing tunable filter by changing the angle of incidence is indicated.

关键词： Cellotape Birefringence Lyot Filter