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Slc6a19 deficiency caused marked aminoaciduria in NOD mice. (a) Amino acid abundance measured in urine normalised to osmolality. (b) Plasma amino acid abundance. Samples were collected in the morning from mice 6-8 weeks of age, stored at −80 • C. Amino acid abundance is presented as peak height in arbitrary units (AU). All results are presented as mean ± SEM; * p < 0.05, ** p < 0.01, **** p < 0.0001 Slc6a19 +/+ versus Slc6a19 −/− ; n = 4-6 mice/genotype.
Source publication
High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the Slc6a19 gene encoding the system B(0) neutral amino acid transporter AT1 would reduce the incidence or delay the onset of type 1 dia...
Citations
... The SLC6A19 gene can code the amino acid transporter B0AT1, which is crucial for transporting amino acids in the liver, kidney, and intestine [17]. It is wellknown that the glomeruli in the renal cortex function to produce an ultrafiltrate. ...
... Disturbance in renal reabsorption of glycine can result in hyperglycinuria. Moreover, a defect in oxalate transportation may increase the urine oxalate content and trigger the damage to the renal tubular epithelial cells, which in turn could promote the formation of calcium oxalate stones [17]. The patient in our report did not receive a high-glycine diet or total parenteral nutrition. ...
Background
Hyperglycinuria is a rare disorder, with few reported cases, caused by either a defect in glycine metabolism or a disturbance in renal glycine reabsorption. Genetic findings of hyperglycinuria are rare and have not previously been reported in Chinese young men.
Case presentation
A 24-year-old man presented with a compliant of bilateral lumbago for 1 month. Abdominal computed tomography revealed bilateral kidney stones and right upper ureteral dilatation. The 24-h urine analysis showed high urine oxalate levels of 63 mg/day. Analysis of amino acids in urine revealed that his urinary glycine levels were abnormally high (2.38 µmol/mg creatinine). Whole-exome sequencing detected the SLC6A19 variant c.1278 C > T p. (Cys426). Flexible ureteroscopy with holmium laser lithotripsy was conducted twice to remove his bilateral nephrolithiasis. Postoperative stone biochemical composition analysis revealed that the stones were composed of approximately 70% calcium oxalate monohydrate and 30% calcium oxalate dihydrate. The patient was subsequently diagnosed with hyperglycinuria. Three months after the stone surgery, ultrasonography revealed one nodule under the right thyroid lobe during a health checkup. His serum parathyroid hormone (PTH) levels increased to 392.3 pg/mL. Resection of the right parathyroid nodule was performed, and the histopathological examination confirmed right parathyroid adenoma. During the 2-year follow-up period, nephrolithiasis did not relapse, and serum PTH, calcium, and phosphorus levels were normal.
Conclusion
The SLC6A19 gene may have been significant in the development of hyperglycinuria in a Chinese young man. Further evaluation for the possibility of a glycine excretion disorder could be considered when encountering nephrolithiasis.
... Additionally, two research articles focused on the prevention of T1D incidence and progression using the spontaneous diabetic NOD mouse model. The first, by Waters et al., investigated the role of the SLC6A19 amino acid transporter in the development of T1D using SLC6A19-deficient female NOD mice [15], and the second, by Borg et al., assessed the benefit of the anti-advanced glycation end products drug Alagebrium Chloride as a pre-diabetic therapy and its subsequent effects on pancreatic function [16]. ...
This Special Issue, Islet Biology and Metabolism, was intended as a collection of studies highlighting the importance of the pancreatic islet—in both form and function—to our growing understanding of metabolic physiology and disease [...]
Sepsis is the leading systemic inflammatory response syndrome in worldwide, yet relatively little is known about the genes and signaling pathways involved in sepsis progression. The current investigation aimed to elucidate potential key candidate genes and pathways in sepsis and its associated complications. Next generation sequencing (NGS) dataset (GSE185263) was downloaded from the Gene Expression Omnibus (GEO) database, which included data from 348 sepsis samples and 44 normal control samples. Differentially expressed genes (DEGs) were identified using t-tests in the DESeq2 R package. Next, we made use of the g:Profiler to analyze gene ontology (GO) and REACTOME pathway. Then protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). Furthermore, we constructed miRNA-hub gene regulatory network and TF-hub gene regulatory network among hub genes utilizing miRNet and NetworkAnalyst online databases tool and Cytoscape software. Finally, we performed receiver operating characteristic (ROC) curve analysis of hub genes through the pROC package in R statistical software. In total, 958 DEGs were identified, of which 479 were up regulated and 479 were down regulated. GO and REACTOME results showed that DEGs mainly enriched in regulation of cellular process, response to stimulus, extracellular matrix organization and immune system. The hub genes of PRKN, KIT, FGFR2, GATA3, ERBB3, CDK1, PPARG, H2BC5, H4C4 and CDC20 might be associated with sepsis and its associated complications. Predicted miRNAs (e.g., hsa-mir-548ad-5p and hsa-mir-2113) and TFs (e.g., YAP1 and TBX5) were found to be significantly correlated with sepsis and its associated complications. In conclusion, the DEGs, relative pathways, hub genes, miRNA and TFs identified in the current investigation might help in understanding of the molecular mechanisms underlying sepsis and its associated complications progression and provide potential molecular targets and biomarkers for sepsis and its associated complications.
