scholarly journals Identification of Perturbed Pathways Rendering Susceptibility to Tuberculosis in Type 2 Diabetes Mellitus Patients Using BioNSi Simulation of Integrated Network of Implicated Human Genes

2021 ◽  
Author(s):  
Jyoti Rani ◽  
Anasuya Bhargav ◽  
Malabika Datta ◽  
Urmi Bajpai ◽  
Srinivasan Ramachandran
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
P Value ◽  
Receptor Signaling ◽  
Chronic Hyperglycemia

Abstract Adaptive immune response of the Th1 arm is the main defense against tuberculosis (TB). However, in Type 2 Diabetes Mellitus (T2DM) patients, chronic hyperglycemia and inflammation underlie susceptibility to TB and results in poor TB control. The molecular pathways causing susceptibility of diabetics to tuberculosis is not fully understood. Here, an integrative pathway-based approach is used to investigate the perturbed pathways in T2DM patients rendering susceptibility to TB. We obtained 36 genes implicated in the Type 2 diabetes associated tuberculosis (T2DMTB) from literature. Gene expression analysis on T2DM patients’ data (GSE28168) showed that DEFA1 is differentially expressed at Padj < 0.05. The genes CAMP, CD14, CORO1A, LAMP1, TLR4, IL17F and SOCS3 were differentially expressed in T2DM patients at P value < 0.05. 7 microRNAs associated with these T2DMTB genes were obtained from NetworkAnalyst and verified for their literature evidences. The hsa-miR-146a microRNA was differentially expressed at Padj < 0.05. The human host TB susceptibility genes TNFRSF10A, MSRA, GPR148, SLC37A3, PXK, PROK2, REV3L, PGM1, HIST3H2A, PLAC4, LETM2, EMP2 and were also differentially expressed at Padj < 0.05. We included all these genes and added the remaining 28 genes from the T2DMTB set and the rest of differentially expressed genes at Padj < 0.05 in STRING and obtained a well-connected network with high confidence score greater than 0.7. From this network we extracted the KEGG pathways at FDR < 0.05 and retained only Diabetes and TB pathways among the disease pathways. The network was simulated with BioNSi using gene expression data from GSE26168. The Necroptosis pathway showed the maximum perturbations in T2DM patients, followed by NOD-like receptor signaling, Toll-like receptor signaling, NF-kappa-B signaling and MAPK signaling. These pathways likely underlie susceptibility to TB in T2DM patients.

scholarly journals Transcriptional Profiling and Biological Pathway(s) Analysis of Type 2 Diabetes Mellitus in a Pakistani Population

2020 ◽  
Vol 17 (16) ◽  
pp. 5866
Author(s):  
Zarish Noreen ◽  
Christopher A. Loffredo ◽  
Attya Bhatti ◽  
Jyothirmai J. Simhadri ◽  
Gail Nunlee-Bland ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathway ◽  
Health Concern ◽  
Receptor Signaling ◽  
Small Pilot Study

The epidemic of type 2 diabetes mellitus (T2DM) is an important global health concern. Our earlier epidemiological investigation in Pakistan prompted us to conduct a molecular investigation to decipher the differential genetic pathways of this health condition in relation to non-diabetic controls. Our microarray studies of global gene expression were conducted on the Affymetrix platform using Human Genome U133 Plus 2.0 Array along with Ingenuity Pathway Analysis (IPA) to associate the affected genes with their canonical pathways. High-throughput qRT-PCR TaqMan Low Density Array (TLDA) was performed to validate the selected differentially expressed genes of our interest, viz., ARNT, LEPR, MYC, RRAD, CYP2D6, TP53, APOC1, APOC2, CYP1B1, SLC2A13, and SLC33A1 using a small population validation sample (n = 15 cases and their corresponding matched controls). Overall, our small pilot study revealed a discrete gene expression profile in cases compared to controls. The disease pathways included: Insulin Receptor Signaling, Type II Diabetes Mellitus Signaling, Apoptosis Signaling, Aryl Hydrocarbon Receptor Signaling, p53 Signaling, Mitochondrial Dysfunction, Chronic Myeloid Leukemia Signaling, Parkinson’s Signaling, Molecular Mechanism of Cancer, and Cell Cycle G1/S Checkpoint Regulation, GABA Receptor Signaling, Neuroinflammation Signaling Pathway, Dopamine Receptor Signaling, Sirtuin Signaling Pathway, Oxidative Phosphorylation, LXR/RXR Activation, and Mitochondrial Dysfunction, strongly consistent with the evidence from epidemiological studies. These gene fingerprints could lead to the development of biomarkers for the identification of subgroups at high risk for future disease well ahead of time, before the actual disease becomes visible.

scholarly journals Identification of Circular RNAs Regulating Islet β-Cell Autophagy in Type 2 Diabetes Mellitus

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Chao Bai ◽  
Wenwen Yang ◽  
Yao Lu ◽  
Wei Wei ◽  
Zongbao Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Expression Profile ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Differentially Expressed ◽  
Qrt Pcr

This study is to identify the circular RNA (circRNA) expression profile that is functionally related to pancreatic islet β-cell autophagy and their potential regulation mechanisms in type 2 diabetes mellitus (T2DM). T2DM rat model was constructed by administration of high-fat and high-sugar diet. β-cells were isolated from islets by flow cytometry. CircRNA expression profile in β-cells was detected by circRNA microarrays, and the differentially expressed circRNAs were identified and validated by qRT-PCR. MicroRNA (miRNA) target prediction software and multiple bioinformatic approaches were used to construct a map of circRNA-miRNA interactions for the differentially expressed circRNAs. A total of 825 differentially expressed circular transcripts were identified in T2DM rats compared with control rats, among which 388 were upregulated and 437 were downregulated. Ten circRNAs were identified to have significant differences by qRT-PCR. GO analysis enriched terms such as organelle membrane and protein binding and the top enriched pathways for the circRNAs included MAPK signaling pathway. The differentially expressed circRNAs might involve in MAPK signaling pathway, apoptosis, and Ras signaling pathway. We speculate that these circRNAs, especially rno_circRNA_008565, can regulate the autophagy of islet β-cells via interactions with miRNA. Dysregulation of several circRNAs may play a role in T2DM development, and rno_circRNA_008565 may be a potential regulator of β-cell autophagy.

scholarly journals High-Throughput Sequencing and Exploration of the lncRNA-circRNA-miRNA-mRNA Network in Type 2 Diabetes Mellitus

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Fang Yang ◽  
Yang Chen ◽  
Zhiqiang Xue ◽  
Yaogai Lv ◽  
Li Shen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Regulatory Network ◽  
Differential Expression Analysis ◽  
Differentially Expressed ◽  
Biological Functions ◽  
Ppi Network

Objective. Long noncoding RNA (lncRNA) and circular RNA (circRNA) are receiving increasing attention in diabetes research. However, there are still many unknown lncRNAs and circRNAs that need further study. The aim of this study is to identify new lncRNAs and circRNAs and their potential biological functions in type 2 diabetes mellitus (T2DM). Methods. RNA sequencing and differential expression analysis were used to identify the noncoding RNAs (ncRNAs) and mRNAs that were expressed abnormally between the T2DM and control groups. The competitive endogenous RNA (ceRNA) regulatory network revealed the mechanism of lncRNA and circRNA coregulating gene expression. The biological functions of lncRNA and circRNA were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The candidate hub mRNAs were selected by the protein-protein interaction (PPI) network and validated by using the Gene Expression Omnibus (GEO) database. Results. Differential expression analysis results showed that 441 lncRNAs (366 upregulated and 75 downregulated), 683 circRNAs (354 upregulated and 329 downregulated), 93 miRNAs (63 upregulated and 30 downregulated), and 2923 mRNAs (1156 upregulated and 1779 downregulated) were identified as remarkably differentially expressed in the T2DM group. The ceRNA regulatory network showed that a single lncRNA and circRNA can be associated with multiple miRNAs, and then, they coregulate more mRNAs. Functional analysis showed that differentially expressed lncRNA (DElncRNA) and differentially expressed circRNA (DEcircRNA) may play important roles in the mTOR signaling pathway, lysosomal pathway, apoptosis pathway, and tuberculosis pathway. In addition, PIK3R5, AKT2, and CLTA were hub mRNAs screened out that were enriched in an important pathway by establishing the PPI network. Conclusions. This study is the first study to explore the molecular mechanisms of lncRNA and circRNA in T2DM through the ceRNA network cofounded by lncRNA and circRNA. Our study provides a novel insight into the T2DM from the ceRNA regulatory network.

Wogonin Alleviates Hyperglycemia Through Increased Glucose Entry into Cells Via AKT/GLUT4 Pathway

2019 ◽  
Vol 25 (23) ◽  
pp. 2602-2606 ◽  
Author(s):  
Shahzad Khan ◽  
Mohammad A. Kamal
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Modern World ◽  
Major Health Problem ◽  
Major Health ◽  
Chronic Hyperglycemia ◽  
Main Factor

: Insulin resistance and type 2 Diabetes mellitus resulting in chronic hyperglycemia is a major health problem in the modern world. Many drugs have been tested to control hyperglycemia which is believed to be the main factor behind many of the diabetes-related late-term complications. Wogonin is a famous herbal medicine which has been shown to be effective in controlling diabetes and its complications. In our previous work, we showed that wogonin is beneficial in many ways in controlling diabetic cardiomyopathy. In this review, we mainly explained wogonin anti-hyperglycemic property through AKT/GLUT4 pathway. Here we briefly discussed that wogonin increases Glut4 trafficking to plasma membrane which allows increased entry of glucose and thus alleviates hyperglycemia. Conclusion: Wogonin can be used as an anti-diabetic and anti-hyperglycemic drug and works via AKT/GLUT4 pathway.

PREVALENCE OF HYPERTENSION AMID PATIENTS WITH TYPE-2 DIABETES MELLITUS- AT A TERTIARY LEVEL HOSPITAL IN CENTRAL INDIA

2021 ◽  
pp. 57-59
Author(s):  
Hakimuddin Malvi ◽  
Syed Maqsood Husain
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Central India ◽  
P Value ◽  
Tertiary Level ◽  
Cross Sectional ◽  
Study Results ◽  
Level Hospital

Background: India has been recognized as the diabetes capital of the world by the year of 2025 Hypertension is a signicant danger factor for cardiovascular infection, stroke and ischemic coronary illness. Objective: The aim of this paper is prevalence of hypertension amid patients with type 2 diabetes mellitus- at a tertiary level hospital in central India. Methods: Present work is hospital based cross-sectional study was conduct in Chirayu Medical College & Hospital, Bhopal. The study population consisted of total 300 subjects. Data obtained directly from patients and patients medical les, and the following data were included in the study . Results: The results showed that the after using chi-square test we found that hypertension was signicantly higher p value(<0.05) among female patients (69%),patients with long duration diabetes (77%)10 years and more, also it was signicantly higher among patients with current smokers (69%). Conclusion: In this study the prevalence of hypertension is increasing in patient with T2DM. Hypertension was the most danger factor for micro vascular and macro vascular confusion of T2DM.

scholarly journals Estimation of Aldose Reductase Activity and Malondialdehyde Levels in Patients with Type 2 Diabetes Mellitus

2019 ◽  
Vol 12 (2) ◽  
pp. 1001-1007
Author(s):  
Sandeep Kumar ◽  
Ajay Kumar ◽  
Mohammad Mustufa Khan
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Sugar ◽  
Aldose Reductase ◽  
Pearson Correlation ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
P Value ◽  
Thiobarbituric Acid Reactive Substance

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia due to insufficient secretion or action of insulin.Elevated oxidative stress and diminished antioxidants may play an important role to develop T2DM and its complications. Aldose reductase (AR) enzyme plays a key role in the reduction of glucose to sorbitol by Polyol pathway. To estimate the AR activity and malondialdehyde (MDA) levels and in patients with T2DM. In this case-control study, a total number of 60 subjects (30 T2DM and 30 age-matched controls) wererecruited.Fasting blood sugar (FBS), Post-Prandial blood sugar (PPBS), AR activity and MDA levels were estimated in all the subjects. The AR activity was estimated by nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidation method. The plasma MDA levels were estimated by the thiobarbituric acid reactive substance (TBARS) method. For Statistical analysis, all the data were compared between the two groups by using unpaired t-test. Pearson correlation coefficient was calculated among T2DM. A P value <0.05 was considered as statistically significant for all data analyzed. The mean of FBS, PPBS, AR activity, and MDA levels were found significantly high in T2DM as compared to controls (P<0.001, P<0.001, P<0.001, P<0.001, respectively). A significant positive correlation was found between FBS and PPBS among T2DM (r=0.71, P<0.01). However, There was no significant correlation found between AR activity and MDA level among T2DM (r=0.002, P>0.05). Results showed thatthe mean of FBS, PPBS, AR activity, and MDA levels were found significantly higher in T2DM than controls. There was no significant correlation found between AR activity and MDA level among T2DM.

scholarly journals Hemoglobin Levels in Type 2 Diabetes Mellitus Patients

2021 ◽  
Vol 3 (1) ◽  
pp. 24-29
Author(s):  
Wahyu Anita Khoirin ◽  
Rodhi Hartono
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Medical Records ◽  
Renal Interstitium ◽  
Chronic Hyperglycemia ◽  
Hypoxic Environment ◽  
Age Category

Type 2 diabetes mellitus with chronic hyperglycemia can cause a hypoxic environment in the renal interstitium and can cause kidney disorders (diabetic nephropathy), this can lead to decreased kidney function and the production of erythropoietin produced by peritubular fibroblasts is disrupted, and hemoglobin is not formed optimally and occurs anemia. Thei purposei ofi thisi studyi wasi toi determinei hemoglobini levelsi in patients withi typei 2i diabetesi mellitusi in RSUD. K.R.M.T Wongsonegoro Semarang. This is a descriptive quantitative study, the data comes from the medical records of patients with typei 2i diabetesi mellitusi withi complicationsi ofi diabetici nephropathyi at RSUD K.R.M.T Wongsonegoro Semarang as many as 40 samples with non-probability samplingi itechnique. The results showed that there were 20 men who had decreased hemoglobin levels and 1 person who had normal hemoglobin levels. Meanwhile, in women, 17 people had decreased hemoglobin levels and 2 people had normal hemoglobin levels. Based on the age category, the most were the early elderly as many as 15 people and the least in the late teens and early adults each as many as 2 people. Meanwhile, based on the average level of anemia, more experienced moderate levels of anemia. Hemoglobin levels in patients with type. 2i. diabetesi. mellitusi. withi. complicationsi. ofi. diabetici. nephropathyi. at RSUD K.R.M.T Wongsonegoro Semarang were 40 samples, on average they had low hemoglobin levels.

scholarly journals Echocardiographic evaluation of left ventricular diastolic dysfunction in recently diagnosed type 2 diabetes mellitus

2018 ◽  
Vol 6 (5) ◽  
pp. 1691
Author(s):  
Swapnil Jain ◽  
C. L. Nawal ◽  
Amandeep Singh ◽  
Radhey Shyam Chejara ◽  
Sagar Barasara ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diastolic Dysfunction ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
P Value ◽  
Diabetic Patients ◽  
Ventricular Diastolic Dysfunction

Background: Diastolic dysfunction in patients suffering from diabetes mellitus represents an earlier stage in the natural history of cardiomyopathy. This study was done to assess the left ventricular diastolic dysfunction in recently diagnosed (<5yr) Type 2 Diabetes Mellitus by Echocardiography and also to determine association of glycemic status (by HBA1c levels) with left ventricular diastolic dysfunction (LVDD).Methods: An observational descriptive study involving 100 diabetic patients, taken on first come first serve basis after applying inclusion and exclusion criteria. In all the subjects, other than routine investigations, HbA1c was estimated and echocardiography was done to evaluate LVDD.Results: Mean value of HbA1c in the study was 8.31+ 1.408 %. 63 out of 100 subjects had LVDD. There was significant positive correlation between HbA1c and LVDD (p value <0.001). As HbA1c increased, severity of LVDD increased. In this study, as BMI increased, HbA1c and LVDD increased & both findings were statistically significant (p value =0.001).Conclusion: Our study indicates that myocardial damage in patients with diabetes affects diastolic function before systolic function &higher HbA1C level is strongly associated with presence of LVDD. Patients should be advised strict control of diabetes in order to reduce the risk for developing LVDD which is a precursor for more advanced disease.Keywords: Diabetes mellitus, Diastolic dysfunction, BMI, HbA1c

scholarly journals A STUDY OF SERUM URIC ACID LEVELS IN TYPE 2 DIABETES MELLITUS CASES AND ITS COMPARISON WITH THE SERUM CREATININE LEVELS

2021 ◽  
pp. 20-22
Author(s):  
Shajahan Shajahan ◽  
Koneru Sri Lahari ◽  
P. Kiranmai
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Uric Acid ◽  
Serum Creatinine ◽  
Serum Uric Acid ◽  
Fasting Blood Glucose ◽  
Control Group ◽  
P Value

BACKGROUND:Type 2 Diabetes Mellitus is a major non-communicable disease resulting from insulin resistance and is associated with cardiovascular,neurological and renal complications.Recent studies show association of hyperuricemia and Diabetes Mellitus.Uric acid increases oxidative stress that leads to vascular dysfunction and high intra glomerular pressure leading to renal complications.High serum creatinine is an indicator of renal compromise. OBJECTIVES: To evaluate serum uric acid and serum creatinine levels in type 2 diabetes mellitus patients and to find association between them. METHODOLOGY: The study was conducted in Osmania general hospital. Fifty cases of established Type 2 Diabetes Mellitus formed the study group and 50 normal healthy individuals formed the control group. Serum uric acid, Fasting Blood Glucose (FBS) and serum creatinine were estimated by colorimetric enzymatic methods on Beckman coulter AU5800.Mean values were compared in cases and controls using student t- test.Study group was further studied under 2 subgroups with serum Uric acid < 7 mg/dl and ≥7 mg/dl.In these 2 subgroups the association of Serum uric acid with FBS and creatinine was analysed statistically. RESULTS: Serum uric acid were found high in cases(7.63+/- 3.36)as compared to controls(4.48+/- 1.09) p value < 0.001.Serum creatinine were also high in cases(1.59+/- 1.39 )as compared to controls ( 0.87+/- 0.29) p value <0.005.Study subgroup with serum uric acid ≥7 mg/dl was associated with high creatinine and high fasting blood sugar levels when compared to subgroup with serum uric acid <7 mg/dl. CONCLUSION: Our study showed increased serum uric acid and serum creatinine levels in cases when compared to controls.There was significant association between high serum uric acid and high creatinine levels in cases.Therefore,it is important to measure serum uric acid and serum creatinine levels in diabetics for early detection of renal pathology.

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