scholarly journals Revealing the Angiopathy of Lacrimal Gland Lesion in Type 2 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Junfa Xue ◽  
Bin Zhang ◽  
Shengqian Dou ◽  
Qingjun Zhou ◽  
Min Ding ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Color Doppler ◽  
Vessel Diameter ◽  
Sequencing Analysis ◽  
Mice Model ◽  
Color Doppler Flow Imaging ◽  
Hub Genes ◽  
Vascular Regulation ◽  
Significant Enrichment

For a better understanding of diabetic angiopathy (DA), the potential biomarkers in lacrimal DA and its potential mechanism, we evaluated the morphological and hemodynamic alterations of lacrimal glands (LGs) in patients with type 2 diabetes and healthy counterparts by color Doppler flow imaging (CDFI). We further established a type 2 diabetic mice model and performed hematoxylin-eosin (HE) staining, immunofluorescence staining of CD31, RNA-sequencing analysis, and connectivity map (CMap) analysis. We found atrophy and ischemia in patients with type 2 diabetes and mice models. Furthermore, we identified 846 differentially expressed genes (DEGs) between type 2 diabetes mellitus (T2DM) and vehicle mice by RNA-seq. The gene ontology (GO) analysis indicated significant enrichment of immune system process, regulation of blood circulation, apoptotic, regulation of secretion, regulation of blood vessel diameter, and so on. The molecular complex detection (MCODE) showed 17 genes were involved in the most significant module, and 6/17 genes were involved in vascular disorders. CytoHubba revealed the top 10 hub genes of DEGs, and four hub genes (App, F5, Fgg, and Gas6) related to vascular regulation were identified repeatedly by MCODE and cytoHubba. GeneMANIA analysis demonstrated functions of the four hub genes above and their associated molecules were primarily related to the regulation of circulation and coagulation. CMap analysis found several small molecular compounds to reverse the altered DEGs, including disulfiram, bumetanide, genistein, and so on. Our outputs could empower the novel potential targets to treat lacrimal angiopathy, diabetes dry eye, and other diabetes-related diseases.

scholarly journals Advanced glycation end product levels were correlated with inflammation and carotid atherosclerosis in type 2 diabetes patients

2020 ◽  
Vol 15 (1) ◽  
pp. 364-372 ◽  
Author(s):  
Jie Li ◽  
Haiyan Shangguan ◽  
Xiaoqian Chen ◽  
Xiao Ye ◽  
Bin Zhong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Color Doppler ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Advanced Glycation End Product ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Ifn Γ

AbstractDiabetes mellitus with atherosclerosis (AS) adds to the social burden. This study aimed to investigate whether advanced glycation end product (AGE) levels were correlated with inflammation and carotid AS (CAS) in type 2 diabetes mellitus (T2DM) patients. A total of 50 elderly T2DM patients and 50 age-matched senior healthy subjects were recruited in this study. T2DM patients were classified into two groups based on the intima–media thickness (IMT) of the carotid artery from color Doppler ultrasonography. Patients with IMT > 1 mm were classified into the T2DM + CAS group (n = 28), and patients with IMT < 1 mm were assigned as the T2DM + non-atherosclerosis (NAS) group (n = 22). The plasma levels of AGEs, receptor for AGE (RAGE), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) of all subjects were measured by enzyme-linked immunosorbent assay. The T-lymphocyte subsets were analyzed by a flow detector. T2DM + CAS patients showed significantly higher concentrations of AGEs, RAGE, TNF-α, and IFN-γ in the peripheral blood. The highest levels of CD4+ T cells were observed in the T2DM + CAS group. The AGE level was positively correlated with the concentrations of RAGE, TNF-α, IFN-γ, and CD4+. In summary, the results showed that the levels of AGEs may be correlated with the inflammatory status in T2DM patients with CAS.

Anti-diabetic activity of chemically profiled green tea and black tea extracts in a type 2 diabetes mice model via different mechanisms

2013 ◽  
Vol 5 (4) ◽  
pp. 1784-1793 ◽  
Author(s):  
Wenping Tang ◽  
Shiming Li ◽  
Yue Liu ◽  
Mou-Tuan Huang ◽  
Chi-Tang Ho
Keyword(s):  
Type 2 Diabetes ◽  
Green Tea ◽  
Black Tea ◽  
Mice Model ◽  
Diabetes Mice

scholarly journals The human type 2 diabetes-specific visceral adipose tissue proteome and transcriptome in obesity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicholas J. Carruthers ◽  
Clarissa Strieder-Barboza ◽  
Joseph A. Caruso ◽  
Carmen G. Flesher ◽  
Nicki A. Baker ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Visceral Adipose Tissue ◽  
Sequencing Analysis ◽  
Complement Factor ◽  
Endothelial Protein C Receptor ◽  
Visceral Adipose

AbstractDysfunctional visceral adipose tissue (VAT) in obesity is associated with type 2 diabetes (DM) but underlying mechanisms remain unclear. Our objective in this discovery analysis was to identify genes and proteins regulated by DM to elucidate aberrant cellular metabolic and signaling mediators. We performed label-free proteomics and RNA-sequencing analysis of VAT from female bariatric surgery subjects with DM and without DM (NDM). We quantified 1965 protein groups, 23 proteins, and 372 genes that were differently abundant in DM vs. NDM VAT. Proteins downregulated in DM were related to fatty acid synthesis and mitochondrial function (fatty acid synthase, FASN; dihydrolipoyl dehydrogenase, mitochondrial, E3 component, DLD; succinate dehydrogenase-α, SDHA) while proteins upregulated in DM were associated with innate immunity and transcriptional regulation (vitronectin, VTN; endothelial protein C receptor, EPCR; signal transducer and activator of transcription 5B, STAT5B). Transcriptome indicated defects in innate inflammation, lipid metabolism, and extracellular matrix (ECM) function, and components of complement classical and alternative cascades. The VAT proteome and transcriptome shared 13 biological processes impacted by DM, related to complement activation, cell proliferation and migration, ECM organization, lipid metabolism, and gluconeogenesis. Our data revealed a marked effect of DM in downregulating FASN. We also demonstrate enrichment of complement factor B (CFB), coagulation factor XIII A chain (F13A1), thrombospondin 1 (THBS1), and integrins at mRNA and protein levels, albeit with lower q-values and lack of Western blot or PCR confirmation. Our findings suggest putative mechanisms of VAT dysfunction in DM.

The effects of complex herbal medicine composed of Cornus fructus, Dioscoreae rhizoma, Aurantii fructus, and Mori folium in obese type-2 diabetes mice model

2013 ◽  
Vol 13 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Ki-Suk Kim ◽  
Hea Jung Yang ◽  
Eun-Kyeong Choi ◽  
Min Hee Shin ◽  
Kang-Hoon Kim ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Herbal Medicine ◽  
Mice Model ◽  
Diabetes Mice

scholarly journals Investigation of Candidate Genes and Mechanisms Underlying Obesity Associated Type 2 Diabetes Mellitus Using Bioinformatics Analysis and Screening of Small Drug Molecules 

2020 ◽  
Author(s):  
Prashanth G ◽  
Basavaraj Vastrad ◽  
Anandkumar Tengli ◽  
Chanabasayya Vastrad ◽  
Iranna Kotturshetti
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Plasma Membrane ◽  
Pathway Analysis ◽  
Regulatory Network ◽  
Target Genes ◽  
Hub Genes ◽  
Drug Molecules

Abstract BackgroundObesity associated type 2 diabetes mellitus is a metabolic disorder ; however, the etiology of obesity associated type 2 diabetes mellitus remains largely unknown. There is an urgent need to further broaden the understanding of the development mechanism of obesity associated type 2 diabetes mellitus. MethodsTo screen the differentially expressed genes (DEGs) that may play essential roles in obesity associated type 2 diabetes mellitus, the public expression profiling by high throughput sequencing data (GSE143319) were downloaded and screened for DEGs. Then, Gene Ontology (GO) function analysis and REACTOME pathway analysis were performed. To screen hub and target genes, the protein–protein interaction network, miRNA-target genes regulatory network and TF-target gene regulatory network were constructed. The Receiver operating characteristic (ROC) curve analysis and RT- PCR analysis of hub genes in obesity associated type 2 diabetes mellitus were also analyzed. Final molecular docking studies performed for screening small drug molecules. ResultsThere were 409 up regulated and 411 down regulated genes detected, and the biological processes of the GO analysis were enriched in regulation of ion transmembrane transport, intrinsic component of plasma membrane, transferase activity, transferring phosphorus-containing groups, cell adhesion, integral component of plasma membrane and signaling receptor binding, whereas, the REACTOME pathway analysis was enriched in integration of energy metabolism and extracellular matrix organization. The hub genes CEBPD, TP73, ESR2, TAB1, MAP3K5, FN1, UBD, RUNX1, PIK3R2 and TNF, which might play a essential role in obesity associated type 2 diabetes mellitus was further screened. ConclusionsThe present study could deepen the understanding of the molecular mechanism of obesity associated type 2 diabetes mellitus, which could be useful in developing clinical treatments of obesity associated type 2 diabetes mellitus.

scholarly journals Bioinformatics Analysis of Key Genes and Pathways for Obesity Associated Type 2 Diabetes Mellitus as a Therapeutic Target

2020 ◽  
Author(s):  
Basavaraj Vastrad ◽  
Anandkumar Tengli ◽  
Chanabasayya Vastrad ◽  
Iranna Kotturshetti
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Differentially Expressed Genes ◽  
Regulatory Network ◽  
Metabolic Disorder ◽  
Target Gene ◽  
Bioinformatics Analysis ◽  
Hub Genes

AbstractObesity associated type 2 diabetes mellitus is one of the most common metabolic disorder worldwide. The prognosis of obesity associated type 2 diabetes mellitus patients has remained poor, though considerable efforts have been made to improve the treatment of this metabolic disorder. Therefore, identifying significant differentially expressed genes (DEGs) associated in metabolic disorder advancement and exploiting them as new biomarkers or potential therapeutic targets for metabolic disorder is highly valuable. Differentially expressed genes (DEGs) were screened out from gene expression omnibus (GEO) dataset (GSE132831) and subjected to GO and REACTOME pathway enrichment analyses. The protein - protein interactions network, module analysis, target gene - miRNA regulatory network and target gene - TF regulatory network were constructed, and the top ten hub genes were selected. The relative expression of hub genes was detected in RT-PCR. Furthermore, diagnostic value of hub genes in obesity associated type 2 diabetes mellitus patients was investigated using the receiver operating characteristic (ROC) analysis. Small molecules were predicted for obesity associated type 2 diabetes mellitus by using molecular docking studies. A total of 872 DEGs, including 439 up regulated genes and 432 down regulated genes were observed. Second, functional enrichment analysis showed that these DEGs are mainly involved in the axon guidance, neutrophil degranulation, plasma membrane bounded cell projection organization and cell activation. The top ten hub genes (MYH9, FLNA, DCTN1, CLTC, ERBB2, TCF4, VIM, LRRK2, IFI16 and CAV1) could be utilized as potential diagnostic indicators for obesity associated type 2 diabetes mellitus. The hub genes were validated in obesity associated type 2 diabetes mellitus. This investigation found effective and reliable molecular biomarkers for diagnosis and prognosis by integrated bioinformatics analysis, suggesting new and key therapeutic targets for obesity associated type 2 diabetes mellitus.

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