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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

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

Challenges in predictive modelling of chronic kidney disease:A narrative review

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World Journal of Nephrology 2024年第3期13卷 26-33页

作者： Sukhanshi Khandpur Prabhaker Mishra Shambhavi Mishra swasti Tiwari Department of Molecular Medicine&Biotechnology Sanjay Gandhi Post Graduate Institute of Medical ScienceLucknow 226014Uttar PradeshIndia Department of Biostatistics and Health Informatics Sanjay Gandhi Post Graduate Institute of Medical SciencesLucknow 226014Uttar PradeshIndia Department of Statistics University of LucknowLucknow 226007Uttar PradeshIndia

The exponential rise in the burden of chronic kidney disease(CKD)worldwide has put enormous pressure on the *** modeling of CKD can ease this burden by predicting the future disease occurrence ahead of its *** are various regression methods for predictive modeling based on the distribution of the outcome ***,the accuracy of the predictive model depends on how well the model is developed by taking into account the goodness of fit,choice of covariates,handling of covariates measured on a continuous scale,handling of categorical covariates,and number of outcome events per predictor parameter or sample *** performance of a predictive model on an independent cohort is ***,there are several challenges in the predictive modeling of ***-specific methodological challenges hinder the development of a predictive model that is cost-effective and universally applicable to predict CKD *** this review,we discuss the advantages and challenges of various regression models available for predictive modeling and highlight those best for future CKD prediction.

关键词： Chronic kidney disease Predictive modelling Regression Statistical modelling Methodology