Dicarbonyl Stress and Glyoxalase-1 in Skeletal Muscle: Implications for Insulin Resistance and Type 2 Diabetes

Mey, Jacob T.; Haus, Jacob M.

doi:10.3389/fcvm.2018.00117

Cited by 34 publications

(20 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MGO administration in our study has been shown to induce severe dicarbonyl stress comparable to levels in T2D patients with poorly controlled diabetes. In our study, MGO aggravated glucose intolerance and increased insulin resistance in the tissues of hypertriglyceridaemic rats, corroborating previous findings [13]. Although MGO administration had no effect on ectopic lipid deposition or body weight in the current study, MGO-treated HHTg rats exhibited changes in blood lipid profiles as serum triglycerides were decreased and total serum cholesterol was significantly increased.…”

Section: Discussionsupporting

confidence: 92%

The effect of dicarbonyl stress on the development of kidney dysfunction in metabolic syndrome – a transcriptomic and proteomic approach

et al. 2019

View full text Add to dashboard Cite

Background and aims Dicarbonyl stress plays an important role in the pathogenesis of microvascular complications that precede the formation of advanced glycation end products, and contributes to the development of renal dysfunction. In renal cells, toxic metabolites like methylglyoxal lead to mitochondrial dysfunction and protein structure modifications. In our study, we investigated the effect of methylglyoxal on metabolic, transcriptomic, metabolomic and proteomic profiles in the context of the development of kidney impairment in the model of metabolic syndrome. Materials and methods Dicarbonyl stress was induced by intragastric administration of methylglyoxal (0.5 mg/kg bw for 4 weeks) in a strain of hereditary hypertriglyceridaemic rats with insulin resistance and fatty liver. Results Methylglyoxal administration aggravated glucose intolerance (AUC 0–120 p < 0.05), and increased plasma glucose ( p < 0.01) and insulin ( p < 0.05). Compared to controls, methylglyoxal-treated rats exhibited microalbuminuria ( p < 0.01). Targeted proteomic analysis revealed increases in urinary secretion of pro-inflammatory parameters (MCP-1, IL-6, IL-8), specific collagen IV fragments and extracellular matrix proteins. Urine metabolomic biomarkers in methylglyoxal-treated rats were mainly associated with impairment of membrane phospholipids (8-isoprostane, 4-hydroxynonenal). Decreased levels of glutathione ( p < 0.01) together with diminished activity of glutathione-dependent antioxidant enzymes contributed to oxidative and dicarbonyl stress. Methylglyoxal administration elevated glyoxalase 1 expression ( p < 0.05), involved in methylglyoxal degradation. Based on comparative transcriptomic analysis of the kidney cortex, 96 genes were identified as differentially expressed (FDR < 0.05). Network analysis revealed an over-representation of genes related to oxidative stress and pro-inflammatory signalling pathways as well as an inhibition of angiogenesis suggesting its contribution to renal fibrosis. Conclusion Our results support the hypothesis that dicarbonyl stress plays a key role in renal microvascular complications. At the transcriptome level, methylglyoxal activated oxidative and pro-inflammatory pathways and inhibited angiogenesis. These effects were further supported by the results of urinary proteomic and metabolomic analyses.

show abstract

Section: Discussionsupporting

confidence: 92%

The effect of dicarbonyl stress on the development of kidney dysfunction in metabolic syndrome – a transcriptomic and proteomic approach

et al. 2019

View full text Add to dashboard Cite

show abstract

“… 17 Also, the expression of glyoxalase I (GLO1) was decreased in response to noise, indicating impaired detoxification of methylglyoxal and other reactive aldehydes and accordingly pointing to an altered defense against metabolic stress. 18 Finally, noise reduced the levels of ACE2, an enzyme attached to the outer cell membranes of cells in the lungs, arteries, heart, kidney, and intestines. ACE2 lowers blood pressure by removal of the vasoconstrictor angiotensin II and accordingly its down-regulation by noise will indirectly increase the blood pressure.…”

Section: Discussionmentioning

confidence: 99%

The impact of aircraft noise on vascular and cardiac function in relation to noise event number: a randomized trial

Schmidt

Herzog

Schnorbus

et al. 2020

Cardiovascular Research

View full text Add to dashboard Cite

Abstract Aims Nighttime aircraft noise exposure has been associated with increased risk of hypertension and myocardial infarction, mechanistically linked to sleep disturbance, stress and endothelial dysfunction. It is unclear, whether the most widely used metric to determine noise exposure, equivalent continuous sound level (Leq), is an adequate indicator of the cardiovascular impact induced by different noise patterns. Methods and results In a randomized crossover study, we exposed 70 individuals with established cardiovascular disease or increased cardiovascular risk to two aircraft noise scenarios and one control scenario. Polygraphic recordings, echocardiography and flow-mediated dilation was determined for 3 study nights. The noise patterns consisted of 60 (Noise60) and 120 (Noise120) noise events, respectively, but with comparable Leq, corresponding to a mean value of 45 dB. Mean value of noise during control nights was 37 dB. During the control night, flow-mediated vasodilation (FMD) was 10.02±3.75%, compared to 7.27±3.21% for Noise60 nights and 7.21±3.58% for Noise120 nights (p<0.001). Sleep quality was impaired after noise exposure in both noise scenario nights (p<0.001). Serial echocardiographic assessment demonstrated an increase in the E/E’ ratio, a measure of diastolic function, within the three exposure nights, with a ratio of 6.83±2.26 for the control night, 7.21±2.33 for Noise60 and 7.83±3.07 for Noise120 (p=0.043). Conclusions Nighttime exposure to aircraft noise with similar Leq, but different number of noise events, results in a comparable worsening of vascular function. Adverse effects of nighttime aircraft noise exposure on cardiac function (diastolic dysfunction) seemed stronger the higher number of noise events. Translational perspective With the present field study, we tested whether 60 versus 120 simulated aircraft noise events with an equal average sound pressure level (Leq) have comparable adverse effects on endothelial and diastolic function of the heart of subjects with established cardiovascular disease or at increased cardiovascular risk. The results demonstrated that two different nighttime noise patterns with similar Leq, despite different number of noise events, results in a comparable worsening of vascular and cardiac diastolic function. These results may explain at least in part the increased incidence of coronary heart disease and heart failure being observed in response to nighttime aircraft noise.

show abstract

“…In this pathway, Glo-1, a major MG detoxifying enzyme, catalyzes the first and the rate-limiting step in the removal of MG, and is crucial in protecting cells against oxidative stress [ 18 , 19 ]. A lack of Glo-1 elicits damage to mitochondria due to increased ROS production [ 20 ]. The linkage between a lack of Glo-1 and ROS production, inflammation, and apoptosis has also been causatively demonstrated [ 5 , 21 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

Yoo

Hong

et al. 2020

Antioxidants

View full text Add to dashboard Cite

To investigate the anti-diabetic properties of chebulic acid (CA) associated with the prevention of methyl glyoxal (MG)-induced mitochondrial dysfunction in INS-1 pancreatic β-cells, INS-1 cells were pre-treated with CA (0.5, 1.0, and 2.0 μM) for 48 h and then treated with 2 mM MG for 8 h. The effects of CA and MG on INS-1 cells were evaluated using the following: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; glyoxalase 1 (Glo-1) expression via Western blot and enzyme activity assays; Nrf-2, nuclear factor erythroid 2-related factor 2 protein expression via Western blot assay; reactive oxygen species (ROS) production assay; mRNA expression of mitochondrial dysfunction related components (UCP2, uncoupling protein 2; VDAC1, voltage-dependent anion-selective channel-1; cyt c, cytochrome c via quantitative reverse transcriptase-PCR; mitochondrial membrane potential (MMP); adenosine triphosphate (ATP) synthesis; glucose-stimulated insulin secretion (GSIS) assay. The viability of INS-1 cells was maintained upon pre-treating with CA before exposure to MG. CA upregulated Glo-1 protein expression and enzyme activity in INS-1 cells and prevented MG-induced ROS production. Mitochondrial dysfunction was alleviated by CA pretreatment; this occurred via the downregulation of UCP2, VDAC1, and cyt c mRNA expression and the increase of MMP and ATP synthesis. Further, CA pre-treatment promoted the recovery from MG-induced decrease in GSIS. These results indicated that CA could be employed as a therapeutic agent in diabetes due to its ability to prevent MG-induced development of insulin sensitivity and oxidative stress-induced dysfunction of β-cells.

show abstract

Dicarbonyl Stress and Glyoxalase-1 in Skeletal Muscle: Implications for Insulin Resistance and Type 2 Diabetes

Cited by 34 publications

References 108 publications

The effect of dicarbonyl stress on the development of kidney dysfunction in metabolic syndrome – a transcriptomic and proteomic approach

The effect of dicarbonyl stress on the development of kidney dysfunction in metabolic syndrome – a transcriptomic and proteomic approach

The impact of aircraft noise on vascular and cardiac function in relation to noise event number: a randomized trial

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

Contact Info

Product

Resources

About