Arsenic-Induced Oxidative Stress: Evidence on In Vitro Models of Cardiovascular, Diabetes Mellitus Type 2 and Neurodegenerative Disorders

2011 ◽  
pp. 659-680
Author(s):  
Rubén Ruíz-Ramos ◽  
Patricia Ostrosky-Wegman ◽  
Mariano E. Cebrián
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Neurodegenerative Disorders ◽  
Diabetes Mellitus Type 2 ◽  
In Vitro Models ◽  
Diabetes Mellitus Type

Impact of diabetic serum on endothelial cells: An in-vitro-analysis of endothelial dysfunction in diabetes mellitus type 2

2007 ◽  
Vol 362 (2) ◽  
pp. 238-244 ◽  
Author(s):  
Daniela Münzel ◽  
Karla Lehle ◽  
Frank Haubner ◽  
Christof Schmid ◽  
Dietrich E. Birnbaum ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Diabetes Mellitus Type 2 ◽  
Diabetes Mellitus Type ◽  
Vitro Analysis ◽  
In Vitro Analysis

scholarly journals Novel Metformin Analogues for Treatment of Pancreatic Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1027-A1028
Author(s):  
Lorena P Burton ◽  
Gang Deng ◽  
Cristian D Yanes ◽  
Jaydutt V Vadgama ◽  
Michael E Jung ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Tumor Progression ◽  
Clinical Benefit ◽  
Diabetes Mellitus Type 2 ◽  
Mtor Signaling ◽  
Diabetes Mellitus Type ◽  
Antitumor Effects ◽  
Incidence And Mortality

Abstract Pancreatic ductal adenocarcinoma (PDCA) is a leading cause of cancer death in the US. Patients diagnosed with PDCA generally present with advanced disease with poor prognosis and limited treatment options. African American patients have higher incidence and mortality of PDCA than Caucasian American or any other ethnic group. Different factors have been attributed to contribute to this health disparity, among them higher incidence of Diabetes Mellitus type 2. To address the need for new therapeutic approaches, we note epidemiologic reports that patients with diabetes mellitus-type 2 treated with the biguanide drug metformin, but not other antidiabetic drugs, have a reduced risk of PDCA and an increased survival rate among those with PDCA. The main physiologic effect of metformin is to lower blood glucose and reduce hyperinsulinemia associated with insulin resistance. In the cell, metformin stimulates AMP-activated protein kinase (AMPK) that in turn inhibits mTORC1 which integrates signals from an array of intracellular pathways to regulate cell growth. Recent clinical trials describe modest antiproliferative effects from use of neoadjuvant metformin, but no significant clinical benefit occurred when metformin was dosed at glycemic control levels in patients with advanced cancers. These findings suggest that development of more potent anticancer analogues of metformin may help to boost clinical benefit and patient survival. Hence, we have designed new biguanide analogues of metformin, and screening of these compounds in preclinical PDCA models show that selected analogues are more efficacious in blocking tumor progression than parental metformin at lower doses. Using proliferation assays in vitro, PDCA cells (Panc 1, MIA Paca-2) were treated 72-hrs with metformin or analogues, and greater dose-dependent inhibition of PDCA cell proliferation was found with analogues as compared to metformin (P<0.001). Further, apoptosis was also markedly induced by metformin analogues as compared to parental metformin (P<0.01). Antitumor effects of metformin are attributed in part to activation LKB1-AMPK pathways and downstream blockade of mTOR signaling, which is often increased in PDCA cells. Using PDCA cells treated in vitro with analogues for 24-hrs, we find that analogues induce AMPK phosphorylation and suppression of mTOR signaling, thus blocking protein synthesis and tumor proliferation. With an in vivo PANC 1 xenograft model in nude mice, lead metformin analogues given by oral gavage daily significantly inhibited tumor progression over 28-days as compared to appropriate controls (P<0.0001). Our findings show that selected metformin analogues have potent anticancer activity in preclinical PDCA models and may have promise as new targeted therapeutics for patients afflicted with this deadly disease. [Funded by NIH/NCI R21CA176337 and NIH/NCI U54 CA143930]

scholarly journals Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162082 ◽  
Author(s):  
Annemarie Grindel ◽  
Bianca Guggenberger ◽  
Lukas Eichberger ◽  
Christina Pöppelmeyer ◽  
Michaela Gschaider ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Dna Damage ◽  
Dna Repair ◽  
Diabetes Mellitus Type 2 ◽  
Diabetes Mellitus Type ◽  
Female Patients ◽  
Patients With Diabetes

scholarly journals Oxidative Stress Genes in Diabetes Mellitus Type 2: Association with Diabetic Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Athanasios Roumeliotis ◽  
Stefanos Roumeliotis ◽  
Fotis Tsetsos ◽  
Marianthi Georgitsi ◽  
Panagiotis I. Georgianos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetes Mellitus Type 2 ◽  
Diabetic Kidney Disease ◽  
Diabetes Mellitus Type ◽  
Nucleotide Polymorphisms ◽  
Diabetic Kidney ◽  
Increased Risk

Diabetic type 2 patients compared to nondiabetic patients exhibit an increased risk of developing diabetic kidney disease (DKD), the leading cause of end-stage renal disease. Hyperglycemia, hypertension, oxidative stress (OS), and genetic background are some of the mechanisms and pathways implicated in DKD pathogenesis. However, data on OS pathway susceptibility genes show limited success and conflicting or inconclusive results. Our study is aimed at exploring OS pathway genes and variants which could be associated with DKD. We recruited 121 diabetes mellitus type 2 (DM2) patients with DKD (cases) and 220 DM2, non-DKD patients (control) of Greek origin and performed a case-control association study using genome-wide association data. PLINK and EIGENSOFT were used to analyze the data. Our results indicate 43 single nucleotide polymorphisms with their 21 corresponding genes on the OS pathway possibly contributing or protecting from DKD: SPP1, TPO, TTN, SGO2, NOS3, PDLIM1, CLU, CCS, GPX4, TXNRD2, EPHX2, MTL5, EPX, GPX3, ALOX12, IPCEF1, GSTA, OXR1, GPX6, AOX1, and PRNP. Therefore, a genetic OS background might underlie the complex pathogenesis of DKD in DM2 patients.

Targeting α -(1,4)-Glucosidase in Diabetes Mellitus Type 2: The Role of New Synthetic Coumarins as Potent Inhibitors

2019 ◽  
Vol 18 (27) ◽  
pp. 2327-2337
Author(s):  
Catalina Figueroa-Benavides ◽  
Maria João Matos ◽  
Montserrat Peñaloza-Amion ◽  
Rubén Veas ◽  
Gabriela Valenzuela-Barra ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetes Mellitus Type 2 ◽  
Hydrophobic Interactions ◽  
Docking Studies ◽  
Diabetes Mellitus Type ◽  
Glucosidase Inhibitors ◽  
Pharmacological Targets

Diabetes mellitus type 2 (DMT2) is a metabolic disease characterized by a chronic increase in glycemia that promotes several long-term complications and high mortality. Some enzymes involved in glycaemic control, such as α -(1,4)-glucosidase, have now been established as novel pharmacological targets. Coumarins have shown benefits in attenuating signs and complications of DMT2, including inhibition of this enzyme. In this work, new synthetic coumarins (bearing different amide and aryl substituents) were studied in vitro as inhibitors of α-(1,4)-glucosidase. Among them, five molecules proved to be excellent α-(1,4)-glucosidase inhibitors, being compound 7 (IC50 = 2.19 µM) about 200 times more potent than acarbose, a drug currently used for the treatment of DMT2. In addition, most of the coumarins presented uncompetitive inhibition for the α-(1,4)-glucosidase. Molecular docking studies revealed that coumarins bind to the active site of the enzyme in a more external area comparing to the substrate, without interfering with it, and displaying aromatic and hydrophobic interactions, as well as some hydrogen bonds. According to the results, aromatic interactions with two phenylalanine residues, 157 and 177, were the most common among the studied coumarins. This study is a step forward for the understanding of coumarins as potential anti-diabetic compounds displaying α-(1,4)-glucosidase inhibition.

Analyzing Phytochemicals as Inhibitors of Diabetes Mellitus 2 Causing Proteins based on Computer-Aided Drug Discovery Protocols

2020 ◽  
Vol 10 ◽  
Author(s):  
Sobia Nazir Chaudry ◽  
Waqar Hussain ◽  
Nouman Rasool
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Diabetes Mellitus Type 2 ◽  
Multidrug Resistant ◽  
Diabetes Mellitus Type ◽  
In Vivo Studies ◽  
Fructose 1,6 Bisphosphate

Background: Diabetes Mellitus type 2 is one of the complex diseases, affecting people both in developed and developing countries. Plant extracted compounds known as phytochemicals are worthy because they have various medicinal properties. Objective: The present study aims at the in silico discovery of novel potent inhibitors against Diabetes Mellitus type 2. Methods: A total of 2750 phytochemicals from various medicinal important plants were collected for this study. Origin of these plants was Pakistan and India. The ADMET, molecular docking approaches were used to determine the binding and reactivity of these phytochemicals as Diabetes Mellitus type 2 inhibitors. Results: The ADMET analysis and molecular docking resulted in the selection of 42 phytochemicals (3 against Glucokinase receptor, 22 against Fructose 1,6 Bisphosphate protein and 17 for multidrug-resistant protein) showing high binding affinity as compared to the previously reported inhibitors of Diabetes Mellitus type 2. Conclusions: These 42 phytochemicals can be considered novel inhibitors against Diabetes Mellitus type 2 and can be selected for additional in vitro and in vivo studies to develop a suitable drug against diabetes.

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