A new glycotoxins inhibitor attenuates insulin resistance in liver and fat cells

Afridi, Shabbir Khan; Aftab, Meha Fatima; Murtaza, Munazza; Ghaffar, Safina; Karim, Aneela; Mughal, Uzma Rasool; Khan, Khalid Mohammed; Waraich, Rizwana Sanaullah

doi:10.1016/j.bbrc.2016.05.085

Cited by 14 publications

(3 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 3T3-L1 adipocytes, MGO impaired insulin signaling as indicated by decreased IRS-1 tyrosine phosphorylation and decreased kinase activity of PI3K (265). In addition, prolonged MGO stimulation of 3T3-L1 adipocytes also led to a decline of the antioxidant defense proteins AGER1 and SIRT1 and an upregulation of RAGE and corresponding downstream effects including altered IR and IRS1/2 phosphorylation (6,90). Thus the increase in endogenous MGO accumulation impairs insulin signaling in adipose tissue.…”

Section: E Methylglyoxal and Obesitymentioning

confidence: 98%

Methylglyoxal, a Highly Reactive Dicarbonyl Compound, in Diabetes, Its Vascular Complications, and Other Age-Related Diseases

Schalkwijk

Stehouwer

2020

Physiological Reviews

390

330

View full text Add to dashboard Cite

The formation and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl compound, has been implicated in the pathogenesis of type 2 diabetes, vascular complications of diabetes, and several other age-related chronic inflammatory diseases such as cardiovascular disease, cancer and disorders of the central nervous system. MGO is mainly formed as a byproduct of glycolysis and, under physiological circumstances, detoxified by the glyoxalase system. MGO is the major precursor of non-enzymatic glycation of proteins and DNA, subsequently leading to the formation of advanced glycation endproducts (AGEs). MGO and MGO-derived AGEs can impact on organs and tissues affecting their functions and structure. This review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system, and its effect on biochemical pathways in relation to the development of diabetes, vascular complications of diabetes and other age-related diseases. Although therapies to treat MGO-associated complications are not yet available for application in clinical practice, several strategies to lower MGO have been developed over the years. We will summarize several new directions to target MGO stress including glyoxalase inducers and MGO scavengers. Diminishing MGO burden can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

show abstract

Section: E Methylglyoxal and Obesitymentioning

confidence: 98%

Methylglyoxal, a Highly Reactive Dicarbonyl Compound, in Diabetes, Its Vascular Complications, and Other Age-Related Diseases

Schalkwijk

Stehouwer

2020

Physiological Reviews

390

330

View full text Add to dashboard Cite

show abstract

“…Recently, Afridi et al. described the anti‐glycation properties of the isatin‐derived compound URM‐II‐81, which was able to attenuate MG‐induced insulin resistance in hepatocytes and adipocytes …”

Section: The Promise Of New Therapeutic Targetsmentioning

confidence: 99%

Methylglyoxal in Metabolic Disorders: Facts, Myths, and Promises

Matafome

Rodrigues

Sena

et al. 2016

Medicinal Research Reviews

View full text Add to dashboard Cite

Glucose and fructose metabolism originates the highly reactive byproduct methylglyoxal (MG), which is a strong precursor of advanced glycation end products (AGE). The MG has been implicated in classical diabetic complications such as retinopathy, nephropathy, and neuropathy, but has also been recently associated with cardiovascular diseases and central nervous system disorders such as cerebrovascular diseases and dementia. Recent studies even suggested its involvement in insulin resistance and beta-cell dysfunction, contributing to the early development of type 2 diabetes and creating a vicious circle between glycation and hyperglycemia. Despite several drugs and natural compounds have been identified in the last years in order to scavenge MG and inhibit AGE formation, we are still far from having an effective strategy to prevent MG-induced mechanisms. This review summarizes the endogenous and exogenous sources of MG, also addressing the current controversy about the importance of exogenous MG sources. The mechanisms by which MG changes cell behavior and its involvement in type 2 diabetes development and complications and the pathophysiological implication are also summarized. Particular emphasis will be given to pathophysiological relevance of studies using higher MG doses, which may have produced biased results. Finally, we also overview the current knowledge about detoxification strategies, including modulation of endogenous enzymatic systems and exogenous compounds able to inhibit MG effects on biological systems.

show abstract

“…In mouse adipocytes (3T3-L1 cells), administration of 0.5 mM MG for 24 h induced intracellular AGE formation, up-regulation of RAGE and increased ROS production [70]. Furthermore, 0.5 mM MG lead to increased tyrosine phosphorylation of PKC-alpha.…”

Section: Effects On Murine Adipocytesmentioning

confidence: 98%

Effects of the Reactive Metabolite Methylglyoxal on Cellular Signalling, Insulin Action and Metabolism – What We Know in Mammals and What We Can Learn From Yeast

Zemva

Pfaff

Groener

et al. 2018

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

Levels of reactive metabolites such as reactive carbonyl and oxygen species are increased in patients with diabetes mellitus. The most important reactive dicarbonyl species, methylglyoxal (MG), formed as by-product during glucose metabolism, is more and more recognized as a trigger for the development and progression of diabetic complications. Although it is clear that MG provokes toxic effects, it is currently not well understood what cellular changes MG induces on a molecular level that may lead to pathophysiological conditions found in long-term diabetic complications. Here we review the current knowledge about the molecular effects that MG can induce in a cell. Within the mammalian system, we will focus mostly on the metabolic effects MG exerts when applied systemically to rodents or when applied to pancreatic β-cells and adipocytes. Due to the common limitations associated with complex model organisms, we then summarize how yeast as a very simple model organism can help to gain valuable comprehensive information on general defence pathways cells exert in response to MG stress. Pioneering studies in additional rather simple eukaryotic model organisms suggest that many cellular reactions in response to MG are highly conserved throughout evolution.

show abstract

A new glycotoxins inhibitor attenuates insulin resistance in liver and fat cells

Cited by 14 publications

References 30 publications

Methylglyoxal, a Highly Reactive Dicarbonyl Compound, in Diabetes, Its Vascular Complications, and Other Age-Related Diseases

Methylglyoxal, a Highly Reactive Dicarbonyl Compound, in Diabetes, Its Vascular Complications, and Other Age-Related Diseases

Methylglyoxal in Metabolic Disorders: Facts, Myths, and Promises

Effects of the Reactive Metabolite Methylglyoxal on Cellular Signalling, Insulin Action and Metabolism – What We Know in Mammals and What We Can Learn From Yeast

Contact Info

Product

Resources

About