In silico analysis of non-synonymous missense SNPs (nsSNPs) in CPE, GNAS genes and experimental validation in type II diabetes mellitus through Next Generation Sequencing

Sabiha, Bibi; Bhatti, Attya; Roomi, Sohaib; John, Peter; Ali, Johar

doi:10.1016/j.ygeno.2021.05.022

Cited by 6 publications

(2 citation statements)

References 60 publications

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“…The Ca(II)/calmodulin-dependent protein kinase II (CaMK II), as a multifunctional enzyme, is highly expressed in the pancreas and is associated with insulin secretion . Furthermore, the GNAS gene is an important regulator of insulin secretory capacity in pancreatic β-cells. , To investigate whether the Mn(II) ions upregulate the insulin expression in T2DM also through the VDCC and GNAS signaling pathways in our study, we performed western blotting analysis using the samples from different groups of T2MD mice. We found that the expressions of GNAS and CaMK II in PC, TPS, and MTNP groups were higher than that of the DC group, while there was no significant difference ( p > 0.05) in the expression level of GNAS among the TPS, ETPS, and MTNP (Figure a,b).…”

Section: Resultsmentioning

confidence: 99%

Mn(II)-Mediated Self-Assembly of Tea Polysaccharide Nanoparticles and Their Functional Role in Mice with Type 2 Diabetes

Fan

Zhang

Zhao

et al. 2022

ACS Appl. Mater. Interfaces

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Tea polysaccharide (TPS) is a bioactive compound that has attracted increasing attention for its health effect on regulating the metabolism of glucose and lipid. Moreover, due to their good biocompatibility and biodegradability, TPS-based nanoparticles have emerged as effective nanocarriers for the delivery of bioactive molecules. In this study, we developed a TPS-based biocarrier system for the orally targeted administration of Mn(II) ions and investigated their antidiabetic effects in C57BL/6 mice with HFD/streptozotocin (STZ)-induced T2DM. Mn(II)-loaded TPS-based nanoparticles (MTNPs) were synthesized, in which negatively charged functional groups in protein and uronic acid in TPS conjugates would act as binding sites for Mn(II) ions, which is responsible for the cross-linking reaction of MTNP. The resulting MTNP had a spherical shape and a mean particle size of around 30 nm with a Mn(II) ion content of 2.24 ± 0.13 mg/g. In T2DM mice, we discovered that MTNP treatment significantly lowered blood glucose levels and improved glucose intolerance. Furthermore, the impact of MTNP on the recovery of FINS, the homeostatic index of insulin resistance (HOMA-IR), and the homeostatic index of β-cell (HOMA β-cell) levels was significantly larger (p < 0.05) than TPS alone, demonstrating that Mn(II) ions can enhance TPS's ability to repair HFD/STZ-induced β-cell damage. Mn(II) ions in MTNP not only acted as cofactors to increase the exocytosis of insulin secretory cells by upregulating the expression of Ca(II)/calmodulin-dependent protein kinase II (CaMK II) but also promoted TPS's lipid-lowering effect in T2DM mice by inhibiting glucogenesis and regulating the lipid metabolism. Our findings suggest that Mn(II) ions can be used not only as cross-linkers in the formation of nanoparticulated TPS but also as cofactors in improving the functional role of TPS in regulating the glucose and lipid metabolism, which will provide insights into the development of TPS-based drug delivery systems for the prevention of type 2 diabetes.

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Section: Resultsmentioning

confidence: 99%

Mn(II)-Mediated Self-Assembly of Tea Polysaccharide Nanoparticles and Their Functional Role in Mice with Type 2 Diabetes

Fan

Zhang

Zhao

et al. 2022

ACS Appl. Mater. Interfaces

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“…A recent study has reported that INS could be regulated by m6A modification, providing a prediction for the occurrence of T2D ( 74 ). Most of the other hub genes, including GCG ( 75 ), NEUROD1 ( 76 ), PCSK1 ( 77 ), ABCC8 ( 78 ), STMN2 ( 79 ), IAPP ( 80 ), KCNQ1 ( 81 ), NKX2-2 ( 82 ), SCG5 ( 83 ), CPE , and GNAS ( 84 ), have been strongly associated with the onset or development of T2D. CHGA , GAD2 , GRIA2 , CHGB , and SLC17A6 have not been previously reported to be associated with T2D.…”

Section: Discussionmentioning

confidence: 99%

Bulk and single-cell transcriptome analyses of islet tissue unravel gene signatures associated with pyroptosis and immune infiltration in type 2 diabetes

Song

Jiang

et al. 2023

Front. Endocrinol.

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IntroductionType 2 diabetes (T2D) is a common chronic heterogeneous metabolic disorder. However, the roles of pyroptosis and infiltrating immune cells in islet dysfunction of patients with T2D have yet to be explored. In this study, we aimed to explore potential crucial genes and pathways associated with pyroptosis and immune infiltration in T2D.MethodsTo achieve this, we performed a conjoint analysis of three bulk RNA-seq datasets of islets to identify T2D-related differentially expressed genes (DEGs). After grouping the islet samples according to their ESTIMATE immune scores, we identified immune- and T2D-related DEGs. A clinical prediction model based on pyroptosis-related genes for T2D was constructed. Weighted gene co-expression network analysis was performed to identify genes positively correlated with pyroptosis-related pathways. A protein–protein interaction network was established to identify pyroptosis-related hub genes. We constructed miRNA and transcriptional networks based on the pyroptosis-related hub genes and performed functional analyses. Single-cell RNA-seq (scRNA-seq) was conducted using the GSE153885 dataset. Dimensionality was reduced using principal component analysis and t-distributed statistical neighbor embedding, and cells were clustered using Seurat. Different cell types were subjected to differential gene expression analysis and gene set enrichment analysis (GSEA). Cell–cell communication and pseudotime trajectory analyses were conducted using the samples from patients with T2D.ResultsWe identified 17 pyroptosis-related hub genes. We determined the abundance of 13 immune cell types in the merged matrix and found that these cell types were correlated with the 17 pyroptosis-related hub genes. Analysis of the scRNA-seq dataset of 1892 islet samples from patients with T2D and controls revealed 11 clusters. INS and IAPP were determined to be pyroptosis-related and candidate hub genes among the 11 clusters. GSEA of the 11 clusters demonstrated that the myc, G2M checkpoint, and E2F pathways were significantly upregulated in clusters with several differentially enriched pathways.DiscussionThis study elucidates the gene signatures associated with pyroptosis and immune infiltration in T2D and provides a critical resource for understanding of islet dysfunction and T2D pathogenesis.

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Dielectrophoresis spectroscopy for nucleotide identification in DNA

Shahriar,

Kabir,

Piaopiao

2023

Aspects of Molecular Medicine

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In silico analysis of non-synonymous missense SNPs (nsSNPs) in CPE, GNAS genes and experimental validation in type II diabetes mellitus through Next Generation Sequencing

Cited by 6 publications

References 60 publications

Mn(II)-Mediated Self-Assembly of Tea Polysaccharide Nanoparticles and Their Functional Role in Mice with Type 2 Diabetes

Mn(II)-Mediated Self-Assembly of Tea Polysaccharide Nanoparticles and Their Functional Role in Mice with Type 2 Diabetes

Bulk and single-cell transcriptome analyses of islet tissue unravel gene signatures associated with pyroptosis and immune infiltration in type 2 diabetes

Dielectrophoresis spectroscopy for nucleotide identification in DNA

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