scholarly journals Constitution of a comprehensive phytochemical profile and network pharmacology based investigation to decipher molecular mechanisms of Teucrium polium L. in the treatment of type 2 diabetes mellitus

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10111
Author(s):  
Vahap Murat Kutluay ◽  
Neziha Yagmur Diker
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Network Pharmacology ◽  
Teucrium Polium ◽  
Phytochemical Profile

Background Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting a huge population worldwide. Teucrium polium L. has been used as a folk medicine for the treatment of T2DM in Anatolia, Turkey. The antihyperglycemic effect of the plant was reported previously. However, there was no detailed study on the underlying molecular mechanisms. In this study, we generated a research plan to clarify the active constituents of the extract and uncover the molecular mechanisms using network pharmacology analysis. Methods For this purpose, we composed a dataset of 126 compounds for the phytochemical profile of the aerial parts of T. polium. Drug-likeness of the compounds was evaluated, and 52 compounds were selected for further investigation. A total of 252 T2DM related targets hit by selected compounds were subjected to DAVID database. Results The KEGG pathway analysis showed enrichment for the TNF signaling pathway, insulin resistance, the HIF-1 signaling pathway, apoptosis, the PI3K-AKT signaling pathway, the FOXO signaling pathway, the insulin signaling pathway, and type 2 diabetes mellitus which are related to T2DM . AKT1, IL6, STAT3, TP53, INS, and VEGFA were found to be key targets in protein-protein interaction. Besides these key targets, with this study the role of GSK3β, GLUT4, and PDX1 were also discussed through literature and considered as important targets in the antidiabetic effect of T. polium. Various compounds of T. polium were shown to interact with the key targets activating PI3K-AKT and insulin signaling pathways. Conclusions According to these findings, mainly phenolic compounds were identified as the active components and IRS1/PI3K/AKT signaling and insulin resistance were identified as the main pathways regulated by T. polium. This study reveals the relationship of the compounds in T. polium with the targets of T2DM in human. Our findings suggested the use of T. polium as an effective herbal drug in the treatment of T2DM and provides new insights for further research on the antidiabetic effect of T. polium.

scholarly journals Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1236
Author(s):  
Jesús Burillo ◽  
Patricia Marqués ◽  
Beatriz Jiménez ◽  
Carlos González-Blanco ◽  
Manuel Benito ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Progressive Disease

Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.

scholarly journals Use of Network Pharmacology to Explore the Mechanism of Gegen (Puerariae lobatae Radix) in the Treatment of Type 2 Diabetes Mellitus Associated with Hyperlipidemia

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Guozhen Yuan ◽  
Shuai Shi ◽  
Qiulei Jia ◽  
Jingjing Shi ◽  
Shuqing Shi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Fluid Shear Stress ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Active Ingredients

Rapid increases in metabolic disorders, such as type 2 diabetes mellitus (T2DM) and hyperlipidemia, are becoming a substantial challenge to worldwide public health. Traditional Chinese medicine has a long history and abundant experience in the treatment of diabetes and hyperlipidemia, and Puerariae lobatae Radix (known as Gegen in Chinese) is one of the most prevalent Chinese herbs applied to treat these diseases. The underlying mechanism by which Gegen simultaneously treats diabetes and hyperlipidemia, however, has not been clearly elucidated to date. Therefore, we systematically explored the potential mechanism of Gegen in the treatment of T2DM complicated with hyperlipidemia based on network pharmacology. We screened the potential targets of Gegen, T2DM, and hyperlipidemia in several online databases. Then, the hub targets were analyzed by performing protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays, and finally, the complicated connections among compounds, targets, and pathways were visualized in Cytoscape. We found that isoflavones, including daidzein, genistein, and puerarin, as well as β-sitosterol, are the key active ingredients of Gegen responsible for its antidiabetic and antihyperlipidemia effects, which mainly target AKR1B1, EGFR, ESR, TNF, NOS3, MAPK3, PPAR, CYP19A1, INS, IL6, and SORD and multiple pathways, such as the PI3K-Akt signaling pathway; the AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis; the PPAR signaling pathway; insulin resistance; the HIF-1 signaling pathway; the TNF signaling pathway; and others. These active ingredients also target multiple biological processes, including the regulation of glucose and lipid metabolism, the maintenance of metabolic homeostasis, and anti-inflammatory and antioxidant pathways. In conclusion, Gegen is a promising therapeutic phytomedicine for T2DM with hyperlipidemia that targets multiple proteins, biological processes, and pathways.

scholarly journals N1-Methylnicotinamide Improves Hepatic Insulin Sensitivity via Activation of SIRT1 and Inhibition of FOXO1 Acetylation

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jingfan Zhang ◽  
Yu Chen ◽  
Cong Liu ◽  
Ling Li ◽  
Ping Li
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Related Proteins

Objective. To explore the effects of N1-methylnicotinamide (MNAM) on insulin resistance and glucose metabolism in obese type 2 diabetes mellitus (T2DM) mice and regulatory mechanisms of the NAD-dependent deacetylase sirtuin-1 (SIRT1)/forkhead box protein O1 (FOXO1) pathway. Methods. Blood glucose and insulin levels were examined in mice. HE and oil red O staining were used to observe the effects of MNAM on liver lipid deposition in ob/ob mice. Real-time PCR and Western blotting were used to detect expression of gluconeogenesis, insulin signaling-related proteins, and SIRT1/FOXO1 pathway-related proteins. L-O2 cells were cultured as a model of insulin resistance, and MNAM and SIRT1 inhibitors were administered in vivo. Residual glucose and insulin signaling-related proteins were detected and the mechanisms associated with the SIRT1/FOXO1 signaling pathway in insulin resistance explored. Results. MNAM can effectively reduce levels of fasting blood glucose and insulin, improve liver morphology, and reduce lipid accumulation in obese type 2 diabetes mellitus mice. MNAM also downregulates the key proteins in the gluconeogenesis pathway in the liver, upregulates Sirt1 expression, and reduces acetylation of the FOXO1 protein. In vitro, MNAM could promote the glucose uptake capacity of L-O2 cells induced by palmitic acid (PA), a saturated fatty acid that induces IR in various scenarios, including hepatocytes, improving insulin resistance. As Sirt1 expression was inhibited, the reduction of hepatocyte gluconeogenesis and the regulation of the insulin signaling pathway by MNAM were reversed. Conclusion. MNAM activates SIRT1 and inhibits acetylation of FOXO1, which in turn regulates insulin sensitivity in type 2 diabetic mice, leading to a reduction of hepatic glucose output and improvement of insulin resistance.

scholarly journals Molecular mechanisms linking peri-implantitis and type 2 diabetes mellitus revealed by transcriptomic analysis

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7124 ◽  
Author(s):  
Tianliang Yu ◽  
Aneesha Acharya ◽  
Nikos Mattheos ◽  
Simin Li ◽  
Dirk Ziebolz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Cross Talk ◽  
Molecular Mechanisms ◽  
Hub Genes ◽  
Ppi Networks

Aims To explore molecular mechanisms that link peri-implantitis and type 2 diabetes mellitus (T2DM) by bioinformatic analysis of publicly available experimental transcriptomic data. Materials and methods Gene expression data from peri-implantitis were downloaded from the Gene Expression Omnibus database, integrated and differentially expressed genes (DEGs) in peri-implantitis were identified. Next, experimentally validated and computationally predicted genes related to T2DM were downloaded from the DisGeNET database. Protein–protein interaction network (PPI) pairs of DEGs related to peri-implantitis and T2DM related genes were constructed, “hub” genes and overlapping DEG were determined. Functional enrichment analysis was used to identify significant shared biological processes and signaling pathways. The PPI networks were subjected to cluster and specific class analysis for identifying “leader” genes. Module network analysis of the merged PPI network identified common or cross-talk genes connecting the two networks. Results A total of 92 DEGs overlapped between peri-implantitis and T2DM datasets. Three hub genes (IL-6, NFKB1, and PIK3CG) had the highest degree in PPI networks of both peri-implantitis and T2DM. Three leader genes (PSMD10, SOS1, WASF3), eight cross-talk genes (PSMD10, PSMD6, EIF2S1, GSTP1, DNAJC3, SEC61A1, MAPT, and NME1), and one signaling pathway (IL-17 signaling) emerged as peri-implantitis and T2DM linkage mechanisms. Conclusions Exploration of available transcriptomic datasets revealed IL-6, NFKB1, and PIK3CG expression along with the IL-17 signaling pathway as top candidate molecular linkage mechanisms between peri-implantitis and T2DM.

2469-PUB: Exploring the Mechanisms of Berberine against Type 2 Diabetes Mellitus and Its Complications by Network Pharmacology

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2469-PUB
Author(s):  
SHA DI ◽  
LIN HAN ◽  
LINHUA ZHAO ◽  
XIAOLIN TONG
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Network Pharmacology
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