scholarly journals Protective Effects of Transient Glucose Exposure in Adult C. elegans

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 160
Author(s):  
Katharina Murillo ◽  
Azat Samigullin ◽  
Per M. Humpert ◽  
Thomas Fleming ◽  
Kübra Özer ◽  
...  

C. elegans are used to study molecular pathways, linking high glucose levels (HG) to diabetic complications. Persistent exposure of C. elegans to a HG environment induces the mitochondrial formation of reactive oxygen species (ROS) and advanced glycation endproducts (AGEs), leading to neuronal damage and decreased lifespan. Studies suggest that transient high glucose exposure (TGE) exerts different effects than persistent exposure. Thus, the effects of TGE on ROS, AGE-formation and life span were studied in C. elegans. Four-day TGE (400 mM) as compared to controls (0mM) showed a persistent increase of ROS (4-days 286 ± 40 RLUs vs. control 187 ± 23 RLUs) without increased formation of AGEs. TGE increased body motility (1-day 0.14 ± 0.02; 4-days 0.15 ± 0.01; 6-days 0.16 ± 0.02 vs. control 0.10 ± 0.02 in mm/s), and bending angle (1-day 17.7 ± 1.55; 3-days 18.7 ± 1.39; 6-days 20.3 ± 0.61 vs. control 15.3 ± 1.63 in degree/s) as signs of neuronal damage. Lifespan was increased by 27% (21 ± 2.4 days) after one-day TGE, 34% (22 ± 1.2 days) after four-days TGE, and 26% (21 ± 1.4 days) after six-days TGE vs. control (16 ± 1.3 days). These experiments suggest that TGE in C. elegans has positive effects on life span and neuronal function, associated with mildly increased ROS-formation. From the perspective of metabolic memory, hormetic effects outweighed the detrimental effects of a HG environment.

Author(s):  
Novi Khila Firani ◽  
Bambang Prijadi

Retinol is one of the active forms of vitamin A. In the previous study, it was known that retinol level in serum of DM patient waslower than in healthy people, which correlated with an increase of the glucose levels in these patients. The importance of retinol in insulinsignaling mechanisms that play a role in the pathogenesis of DM is still unknown. One of the components that play a role in insulinsignaling on adipocytes is phosphatidylinositol-3 kinase (PI3K), which encourages the translocation of glucose transporter-4 (GLUT4) tothe cell surface. The aim of this study was to know the importance of retinol therapy in the levels of PI3K enzyme on visceral adipocyteculture with high glucose exposure (25 mM) as a model of DM in vitro by determination method. Retinol therapy was given at a doseof 0.1 μM, 1 μM , and 10 μM. Measurement of PI3K level was done by ELISA method. The mean (SD) levels of PI3K enzyme were 1.91(0.27), 0.94 (0.15), 1.98 (0.22), 1.69 (0.81), 2.04 (0.16) ng/mL respectively, for adipocyte cultures exposed to 5mM glucose (as aphysiological condition), 25mM glucose, and 25mM glucose concentration with doses of retinol therapy 0.1 μM, 1 μM and10 μM. Theresults of this study indicated that high glucose exposure (25 mM) decreased the level of PI3K compared with adipocyte’s culture on5 mM glucose exposure. Retinol therapy with a dose of 0.1μM, 1μM and10 μM on adipocyte culture exposed with high glucose couldincrease the levels of PI3K.


Diabetes ◽  
2009 ◽  
Vol 58 (11) ◽  
pp. 2450-2456 ◽  
Author(s):  
A. Schlotterer ◽  
G. Kukudov ◽  
F. Bozorgmehr ◽  
H. Hutter ◽  
X. Du ◽  
...  
Keyword(s):  

2012 ◽  
Vol 302 (4) ◽  
pp. C666-C675 ◽  
Author(s):  
Subhadeep Chakrabarti ◽  
Christopher C. Cheung ◽  
Sandra T. Davidge

Hyperglycemia in diabetes causes increased oxidative stress in the vascular endothelium with generation of free radicals such as superoxide. Peroxynitrite, a highly reactive species generated from superoxide and nitric oxide (NO), induces proinflammatory tyrosine nitration of intracellular proteins under such conditions. The female sex hormone estrogen appears to exert protective effects on the nondiabetic endothelium. However, several studies show reduced vascular protection in women with diabetes, suggesting alterations in estrogen signaling under high glucose. In this study, we examined the endothelial effects of estrogen under increasing glucose levels, focusing on nitrotyrosine and peroxynitrite. Human umbilical vein endothelial cells were incubated with normal (5.5 mM) or high (15.5 or 30.5 mM) glucose before addition of estradiol (E2, 1 or 10 nM). Selective NO synthase (NOS) inhibitors were used to determine the role of specific NOS isoforms. Addition of E2 significantly reduced high glucose-induced increase in peroxynitrite and consequently, nitrotyrosine. The superoxide levels were unchanged, suggesting effects on NO generation. Inhibition of neuronal NOS (nNOS) reduced high glucose-induced nitrotyrosine, demonstrating a critical role for this enzyme. E2 increased nNOS activity under normal glucose while decreasing it under high glucose as determined by its phosphorylation status. These data show that nNOS contributes to endothelial peroxynitrite and subsequent nitrotyrosine generation under high glucose, which can be attenuated by E2 through nNOS inhibition. The altered regulation of nNOS by E2 under high glucose is a potential therapeutic target in women with diabetes.


2021 ◽  
Author(s):  
Xiao Zhu ◽  
Yihan Liu ◽  
Jia Cui ◽  
Jianyi Lv ◽  
Changlong Li ◽  
...  

Abstract Background: Long noncoding RNAs (lncRNAs) are involved in diabetes related diseases. However, the role of lncRNAs in the pathogenesis of type 2 diabetes with macrovascular complication (DMC) has seldomly been recognized. This study aimed to screen lncRNA profiles of leukocytes from DMC patients in order to explore the protective role of lncRNA LYPLAL1-DT in endothelial cells (EC) under high glucose (HG) and inflammatory conditions (IS).Methods: RNA sequencing was performed for critically pair-grouped blood samples of DMC patients and healthy control. Then the differentially expressed (DE) lncRNAs from circulating leukocytes were identified. Real-time PCR analyses were used to select the DE-lncRNAs within expanding cohorts. CCK8, transwell, Western blot, dual-luciferase system, and RIP were used to investigate the influence and molecular mechanisms of validated DE-lncRNAs in EC under HG and IS conditions. RNA sequencing was also used to identify DE-lncRNAs in exosomes isolated from the DMC serum and healthy control. Results: A total of 477 DE-lncRNAs were identified between DMC and healthy control. The enrichment and pathway analysis showed that most of them belonged to inflammatory, metabolic, and vascular diseases. A set of 12 of the 16 lncRNAs was validated as significant DE-lncRNAs in expanding cohorts. Furthermore, these DE-lncRNAs were shown to be significantly related to hypoxia, high glucose, and TNF-α stimulus (IS) in EC with an apparent metabolic memory of high glucose, especially novel lncRNA LYPLAL1-DT. LYPLAL1-DT overexpression results in the promotion of proliferation, migration of EC, as well as an elevation of autophagy under HG, and IS conditions. Overexpressed LYPLAL1-DT reduces the adhesion of monocytes to EC, boosts anti-inflammation, and suppresses inflammatory molecules secreted in the medium. Mechanistically, LYPLAL1-DT acts as ceRNA by downregulating miR-204-5p, therefore enhancing SIRT1 and protecting EC autophagy function; thus, alleviating apoptosis. Finally, exosome sequencing revealed LYPLAL1-DT expression was 4 times lower in DMC cells than in healthy samples. Conclusion: We identified 12 DE-lncRNAs related to DMC. Out of the 12 DE-lncRNAs lncRNA LYPLAL1-DT was identified to have protective effects on EC as ceRNA mediated through the miR-204-5p/SIRT1 pathway. Therefore, it inhibits the autophagy of EC as well as modulating systemic inflammation. This approach could be regarded as a new potential therapeutic target in DMC.


Author(s):  
Andrea Schlotterer ◽  
Benan Masri ◽  
M. Humpert ◽  
Bernhard Karl Krämer ◽  
Hans-Peter Hammes ◽  
...  

Abstract Caenorhabditis elegans is an established model organism in neurodegeneration and aging research. Oxidative stress and formation of advanced glycation endproducts (AGEs), as they occur under hyperglycemic conditions in diabetes mellitus, contribute to neuronal damage and lifespan reduction. Sulforaphane (SFN) is an indirect antioxidant, alpha-tocopherol (vitamin E) is a direct antioxidant that acts as a free radical scavenger. Aim of this study is to investigate the protective effects of SFN and vitamin E against glucotoxic damages to the neuronal system and lifespan in C. elegans. Culture conditions that mimic clinical hyperglycemia increased the formation of reactive oxygen species (ROS) (p<0.001) and the accumulation of methylglyoxal-derived advanced glycation endproducts (MG-derived AGEs) (p<0.01) with subsequent neuronal damage and neuronal dysfunction, ultimately leading to a significant shortening of lifespan (p<0.01). Treatment with both, 20 µmol/l SFN and 200 µg/ml vitamin E, completely prevented the increase in ROS and MG-derived AGEs, abolished the glucotoxic effects on neuronal structure and function, and preserved lifespan, resulting in a life expectancy similar to untreated controls. These data emphasize the relevance of indirect and direct antioxidants as potential therapeutic options for the prevention of glucotoxic pathologies.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 257-OR
Author(s):  
FRIDA EMANUELSSON ◽  
SARAH MAROTT ◽  
ANNE TYBJAERG-HANSEN ◽  
BØRGE GRØNNE NORDESTGAARD ◽  
MARIANNE BENN

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