Up‐regulation of aldolase <scp>A</scp> and methylglyoxal production in adipocytes

Liu, Jianghai; Desai, Kaushik; Wang, Rui; Wu, Lingyun

doi:10.1111/bph.12046

Cited by 15 publications

(9 citation statements)

References 41 publications

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“…Our data here in part explain the consequential apoptotic signaling pathways initiated by GSNO in ECs. Insulin‐insensitive cells, such as ECs, and insulin‐sensitive cells, such as adipose cells, are traditionally distinguished by their sensitivity to insulin with respect to glucose transport [Liu et al, ]. Glucose enters insulin insensitive ECs mainly through an insulin‐independent GLUT1 [Shepherd and Kahn, ].…”

Section: Discussionmentioning

confidence: 99%

Enhanced Aerobic Glycolysis by S-Nitrosoglutathione via HIF-1α Associated GLUT1/Aldolase A Axis in Human Endothelial Cells

et al. 2017

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S-nitrosoglutathione (GSNO)-induced apoptosis is associated with reactive oxygen species and loss of mitochondrial Omi/HtrA2 in human endothelial cells (ECs). But its upstream regulation is still not elucidated. Here, we demonstrate that hypoxia induced factor-1α (HIF-1α)-linked aerobic glycolysis is associated with mitochondrial abnormality by treatment of human EC-derived EA.hy926 cells with GSNO (500 µM) for 6 h. GSNO exposure increased the levels of Aldolase A and glucose transporter-1 (GLUT1) mRNAs and proteins. And selectively enhanced aldolase A activity to form glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, which subsequently increased intracellular levels of methylglyoxal and reactive oxygen species in parallel. Using the biotin switch assay, we found that GSNO increased the S-nitrosylating levels of total protein and HIF-1α. Knockdown of HIF-1α with siRNA attenuated its target aldolase A and GLUT1 expression but not VEGF. In contrast, nitrosylation scanvenger dithiothreitol could decrease all the protein levels. It suggested that aerobic glycolytic flux was more dependent on HIF-1α level, and that HIF-1α S-nitrosylation was crucial for its target expression under the normoxic condition. Moreover, GSNO-induced PI3 K (phosphoinositide 3-kinase)/Akt phosphorylation might contribute to HIF-1α stabilization and nucleus translocation, thereby aiding aldolase A and GLUT1 mRNAs upregulation. Taken together, higher concentration GSNO promotes glycolytic flux enhancement and methylglyoxal formation via HIF-1α S-nitrosylation. These findings reveal the mechanism of enhanced glycolysis-associated mitochondrial dysfunction in ECs by GSNO exposure under normoxic and non-hyperglycemic condition. And offer the early potential targets for vascular pathophysiological evaluation. J. Cell. Biochem. 118: 2443-2453, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Enhanced Aerobic Glycolysis by S-Nitrosoglutathione via HIF-1α Associated GLUT1/Aldolase A Axis in Human Endothelial Cells

et al. 2017

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“…Liu and his co-workers reported a close correlation between insulin resistance and elevated MG accumulation in adipose and vascular smooth muscle tissues of experimental animals . MG administration impaired insulin signaling as measured by decreased tyrosine phosphorylation of IRS-1 and kinase activity of PI3K .…”

Section: Pathological Consequences Of Mgmentioning

confidence: 93%

Pathophysiological Insights of Methylglyoxal Induced Type-2 Diabetes

Sireesh

Bhakkiyalakshmi

Balashanmugam

et al. 2015

Chem. Res. Toxicol.

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Diabetes mellitus is a metabolic disorder constituting a major health problem whose prevalence has gradually increased worldwide over the past few decades. Type 2 diabetes mellitus (T2DM) remains more complex and heterogeneous and arises as a combination of insulin resistance and inadequate functional β-cell mass and comprises about 90% of all diabetic cases. Appropriate experimental animal models are essential for understanding the molecular basis, pathogenesis of complications, and the utility of therapeutic agents to abrogate this multifaceted disorder. Currently, animal models for T2DM are obtained as spontaneously developed diabetes or diabetes induced by chemicals or dietary manipulations or through surgical or genetic methods. The currently used diabetogenic agents have certain limitations. Recently, methylglyoxal (MG), a highly reactive compound derived mainly from glucose and fructose metabolism has been implicated in diabetic complications. MG is a major precursor of the advanced glycation end product (AGE) and promotes impaired functions of insulin signaling, GLUT transporters, anion channels, kinases, and endothelial cells and is finally involved in apoptosis. Recent array of literature also cited that higher concentrations of MG causes rapid depolarization, elevated intracellular Ca(2+) concentration, and acidification in pancreatic β-cells. This review henceforth highlights the mechanism of action of MG and its implications in the pathophysiology of experimental diabetes.

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“…However, such results were mainly observed in db/db mice, without significant effects on normal mice [57,58]. MG production was observed in adipocytes due to increased Aldolase-A activation and decreased antioxidant defenses [59]. Our group has shown the accumulation of adipose tissue MG at levels similar to diabetic rats following oral administration (75 mg/Kg), but with little effects on adipose tissue insulin signaling [60,61].…”

Section: Development Of Animal Modelsmentioning

confidence: 78%

Another Player in the Field: Involvement of Glycotoxins and Glycosative Stress in Insulin Secretion and Resistance

Matafome

2020

Diabetology

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The term glycotoxins includes the group of advanced glycation end-products (AGEs) and their precursors, most of them highly reactive intermediary compounds, such as methylglyoxal (MG). Glycotoxins were initially thought to participate in the development of diabetic complications because of their increased formation from glucose. However, they also form and accumulate in tissues since the early stages of disease, such as metabolically unhealthy obesity and prediabetes. Such accumulation has been suggested to result from dysregulated activity of detoxification systems, such as the glyoxalase system, as well as increased dietary consumption, namely from high-glucose and high-fructose foods processed at high temperatures. Although some studies may have used supraphysiological doses, in vitro systems and animal models have shown glycotoxin-induced insulin resistance. Moreover, dietary glycotoxin restriction was shown to improve insulin resistance in humans and glyoxalase (GLO)-1 upregulation improved insulin sensitivity and metabolic function. This review summarizes the current knowledge about glycotoxin involvement in the development of insulin resistance, the mechanisms involved and the usefulness of GLO-1 modulation, and a possible therapeutic strategy to improve insulin sensitivity.

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Up‐regulation of aldolase A and methylglyoxal production in adipocytes

Cited by 15 publications

References 41 publications

Enhanced Aerobic Glycolysis by S-Nitrosoglutathione via HIF-1α Associated GLUT1/Aldolase A Axis in Human Endothelial Cells

Enhanced Aerobic Glycolysis by S-Nitrosoglutathione via HIF-1α Associated GLUT1/Aldolase A Axis in Human Endothelial Cells

Pathophysiological Insights of Methylglyoxal Induced Type-2 Diabetes

Another Player in the Field: Involvement of Glycotoxins and Glycosative Stress in Insulin Secretion and Resistance

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