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Specialty: Chemistry
Condition: Diabetes Type 2
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Total 13 results found since Jan 2013.
Molecules, Vol. 26, Pages 1328: Identification of a Sesquiterpene Lactone from Arctium lappa Leaves with Antioxidant Activity in Primary Human Muscle Cells
In this study, we investigated the antioxidant properties of Arctium lappa leaves in a model of primary human muscle cells exposed to H2O2 oxidative stress. We identified using bioassay-guided purification, onopordopicrin, a sesquiterpene lactone as the main molecule responsible for the antioxidant activity of A. lappa leaf extract. According to our findings, onopordopicrin inhibited the H2O2-mediated loss of muscle cell viability, by limiting the production of free radicals and abolishing DNA cellular damages. Moreover, we showed that onopordopicrin promoted the expression of the nuclear factor-erythroid-2-related factor ...
Source: Molecules - March 2, 2021 Category: Chemistry Authors: Nour El Khatib Sylvie Morel G érald Hugon Sylvie Rapior Gilles Carnac Nathalie Saint Tags: Article Source Type: research
Molecules, Vol. 24, Pages 4208: Deficiency of Urokinase Plasminogen Activator May Impair β Cells Regeneration and Insulin Secretion in Type 2 Diabetes Mellitus
Conclusion: uPA may play a substantial role in insulin secretion, β cell regeneration, and progressive development of T2DM. Supplementation of uPA might be a novel approach for prevention and treatment of T2DM in the future.
Source: Molecules - November 19, 2019 Category: Chemistry Authors: Wu Ou Chang Lin Pei Chen Tags: Article Source Type: research
The complement receptor C5aR2 promotes protein kinase R expression and contributes to NLRP3 inflammasome activation and HMGB1 release from macrophages Signal Transduction
In conclusion, these findings reveal that C5aR2 contributes to NLRP3 inflammasome activation and HMGB1 release from macrophages.
Source: Journal of Biological Chemistry - May 23, 2019 Category: Chemistry Authors: Songlin Yu, Dan Wang, Lingmin Huang, Yening Zhang, Ruiheng Luo, Dickson Adah, Yiting Tang, Kai Zhao, Ben Lu Tags: Immunology Source Type: research
Pancreatic {beta}-cells detoxify H2O2 through the peroxiredoxin/thioredoxin antioxidant system Metabolism
Oxidative stress is thought to promote pancreatic β-cell dysfunction and contribute to both type 1 and type 2 diabetes. Reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, are mediators of oxidative stress that arise largely from electron leakage during oxidative phosphorylation. Reports that β-cells express low levels of antioxidant enzymes, including catalase and GSH peroxidases, have supported a model in which β-cells are ill-equipped to detoxify ROS. This hypothesis seems at odds with the essential role of β-cells in the control of metabolic homeostasis and organismal survival through exquisite...
Source: Journal of Biological Chemistry - March 28, 2019 Category: Chemistry Authors: Jennifer S. Stancill, Katarzyna A. Broniowska, Bryndon J. Oleson, Aaron Naatz, John A. Corbett Tags: Signal Transduction Source Type: research
The orphan nuclear receptor Nor1/Nr4a3 is a negative regulator of {beta}-cell mass Molecular Bases of Disease
The Nr4a subfamily of nuclear receptor comprises three members in mammalian cells: Nur77/Nr4a1, Nurr1/Nr4a2, and Nor1/Nr4a3. Nr4a proteins play key roles in the regulation of glucose homeostasis in peripheral metabolic tissues. However, their biological functions in β-cells remain relatively uncharacterized. Here we sought to investigate the potential role of Nor1 in the regulation of β-cell mass and, in particular, β-cell survival/apoptosis. We used histological analysis to examine the consequences of genetic deletion of either Nur77 and Nor1 on β-cell mass, investigated the expression patterns of Nr4as in human islet...
Source: Journal of Biological Chemistry - March 28, 2019 Category: Chemistry Authors: Anne–Francoise Close, Nidheesh Dadheech, Barbara Scoralick Villela, Claude Rouillard, Jean Buteau Tags: Molecular Bases of Disease Source Type: research
Complement 1q-like-3 protein inhibits insulin secretion from pancreatic {beta}-cells via the cell adhesion G protein-coupled receptor BAI3 Cell Biology
Secreted proteins are important metabolic regulators in both healthy and disease states. Here, we sought to investigate the mechanism by which the secreted protein complement 1q-like-3 (C1ql3) regulates insulin secretion from pancreatic β-cells, a key process affecting whole-body glucose metabolism. We found that C1ql3 predominantly inhibits exendin-4– and cAMP-stimulated insulin secretion from mouse and human islets. However, to a lesser extent, C1ql3 also reduced insulin secretion in response to KCl, the potassium channel blocker tolbutamide, and high glucose. Strikingly, C1ql3 did not affect insulin secretion stimula...
Source: Journal of Biological Chemistry - November 23, 2018 Category: Chemistry Authors: Rajesh Gupta, Dan C. Nguyen, Michael D. Schaid, Xia Lei, Appakalai N. Balamurugan, G. William Wong, Jeong-a Kim, James E. Koltes, Michelle E. Kimple, Sushant Bhatnagar Tags: Metabolism Source Type: research
Mitochondrial Activity in Human White Adipocytes Is Regulated by the Ubiquitin Carrier Protein 9/microRNA-30a Axis Cell Biology
In this study, we demonstrate that the mRNA and protein expression of Ubc9 are regulated by the microRNA miRNA-30a (miR-30a) in human subcutaneous adipocytes. Ubc9 and miR-30a exhibit inverse expression in adipose tissue, with miR-30a robustly elevated in brown fat. Depletion of Ubc9 by siRNA or enforced expression of a miR-30a mimic augments mitochondrial volume and respiration in human white adipocytes, reflecting features of brown fat cells. Furthermore, Ubc9 depletion induces a brown fat gene program in human subcutaneous adipocytes. Induction of the beige-selective gene program corresponds to stabilization of the PR d...
Source: Journal of Biological Chemistry - November 17, 2016 Category: Chemistry Authors: Eun Hee Koh, Yong Chen, David A. Bader, Mark P. Hamilton, Bin He, Brian York, Shingo Kajimura, Sean E. McGuire, Sean M. Hartig Tags: Gene Regulation Source Type: research
PFKFB3 and Insulin Signalling Metabolism
The insulin/insulin-like growth factor (IGF)-1 signaling pathway (ISP) plays a fundamental role in long term health in a range of organisms. Protein kinases including Akt and ERK are intimately involved in the ISP. To identify other kinases that may participate in this pathway or intersect with it in a regulatory manner, we performed a whole kinome (779 kinases) siRNA screen for positive or negative regulators of the ISP, using GLUT4 translocation to the cell surface as an output for pathway activity. We identified PFKFB3, a positive regulator of glycolysis that is highly expressed in cancer cells and adipocytes, as a posi...
Source: Journal of Biological Chemistry - October 23, 2015 Category: Chemistry Authors: Trefely, S., Khoo, P.–S., Krycer, J. R., Chaudhuri, R., Fazakerley, D. J., Parker, B. L., Sultani, G., Lee, J., Stephan, J.–P., Torres, E., Jung, K., Kuiȷl, C., James, D. E., Junutula, J. R., Stockli, J. Tags: Signal Transduction Source Type: research
Zfp407 Regulates Adipose Glucose Uptake Gene Regulation
The glucose transporter GLUT4 facilitates insulin-stimulated glucose uptake in peripheral tissues including adipose, muscle, and heart. GLUT4 function is impaired in obesity and type 2 diabetes leading to hyperglycemia and an increased risk of cardiovascular disease and neuropathy. To better understand the regulation of GLUT4 function, a targeted siRNA screen was performed and led to the discovery that ZFP407 regulates insulin-stimulated glucose uptake in adipocytes. The decrease in insulin-stimulated glucose uptake due to ZFP407 deficiency was attributed to a reduction in GLUT4 mRNA and protein levels. The decrease in GLU...
Source: Journal of Biological Chemistry - March 5, 2015 Category: Chemistry Authors: Buchner, D. A., Charrier, A., Srinivasan, E., Wang, L., Paulsen, M. T., Ljungman, M., Bridges, D., Saltiel, A. R. Tags: Metabolism Source Type: research
Atf3/Pdx-1/Hdac1 Axis Prompts Metabolic Syndrome Gene Regulation
Chronic ethanol consumption induces pancreatic β-cell dysfunction through glucokinase (Gck) nitration and down-regulation, leading to impaired glucose tolerance and insulin resistance, but the underlying mechanism remains largely unknown. Here, we demonstrate that Gck gene expression and promoter activity in pancreatic β-cells were suppressed by chronic ethanol exposure in vivo and in vitro, whereas expression of activating transcription factor 3 (Atf3) and its binding to the putative Atf/Creb site (from −287 to −158 bp) on the Gck promoter were up-regulated. Furthermore, in vitro ethanol-induced Atf3 inhibited the p...
Source: Journal of Biological Chemistry - September 25, 2014 Category: Chemistry Authors: Kim, J. Y., Hwang, J.-Y., Lee, D. Y., Song, E. H., Park, K. J., Kim, G. H., Jeong, E. A., Lee, Y. J., Go, M. J., Kim, D. J., Lee, S. S., Kim, B.-J., Song, J., Roh, G. S., Gao, B., Kim, W.-H. Tags: Molecular Bases of Disease Source Type: research
Insulin, NF-{kappa}B, and Myocardin Signaling in Cardiac Myoblasts Signal Transduction
Hyperinsulinemia contributes to cardiac hypertrophy and heart failure in patients with the metabolic syndrome and type 2 diabetes. Here, high circulating levels of tumor necrosis factor (TNF)-α may synergize with insulin in signaling inflammation and cardiac hypertrophy. We tested whether high insulin affects activation of TNF-α-induced NF-κB and myocardin/serum response factor (SRF) to convey hypertrophy signaling in cardiac myoblasts. In canine cardiac myoblasts, treatment with high insulin (10−8 to 10−7 m) for 0–24 h increased insulin receptor substrate (IRS)-1 phosphorylation at Ser-307, decreased protein leve...
Source: Journal of Biological Chemistry - July 10, 2014 Category: Chemistry Authors: Madonna, R., Geng, Y.-J., Bolli, R., Rokosh, G., Ferdinandy, P., Patterson, C., De Caterina, R. Tags: Gene Regulation Source Type: research
CTSB Contributes to Atg7-induced Proinflammatory Response Metabolism
Impairment of glucose-stimulated insulin secretion caused by the lipotoxicity of palmitate was found in β-cells. Recent studies have indicated that defects in autophagy contribute to pathogenesis in type 2 diabetes. Here, we report that autophagy-related 7 (Atg7) induced excessive autophagic activation in INS-1(823/13) cells exposed to saturated fatty acids. Atg7-induced cathepsin B (CTSB) overexpression resulted in an unexpected significant increase in proinflammatory chemokine and cytokine production levels of IL-1β, monocyte chemotactic protein-1, IL-6, and TNF-α. Inhibition of receptor-interacting protein did not af...
Source: Journal of Biological Chemistry - October 18, 2013 Category: Chemistry Authors: Li, S., Du, L., Zhang, L., Hu, Y., Xia, W., Wu, J., Zhu, J., Chen, L., Zhu, F., Li, C., Yang, S. Tags: Cell Biology Source Type: research
Manganese, ICAM-1, MCP-1, and Endothelial Cell Dysfunction Molecular Bases of Disease
This study examines the hypothesis that Mn2+ supplementation can reduce the markers/risk factors of endothelial dysfunction in type 2 diabetes. Human umbilical vein endothelial cells (HUVECs) were cultured with or without Mn2+ supplementation and then exposed to high glucose (HG, 25 mm) to mimic diabetic conditions. Mn2+ supplementation caused a reduction in monocyte adhesion to HUVECs treated with HG or MCP-1. Mn2+ also inhibited ROS levels, MCP-1 secretion, and ICAM-1 up-regulation in HUVECs treated with HG. Silencing studies using siRNA against MnSOD showed that similar results were observed in MnSOD knockdown HUVECs fo...
Source: Journal of Biological Chemistry - March 1, 2013 Category: Chemistry Authors: Burlet, E., Jain, S. K. Tags: Metabolism Source Type: research
