Methylglyoxal, a potent inducer of AGEs, connects between diabetes and cancer

Bellier, Justine; Nokin, Marie-Julie; Lardé, Eva; Karoyan, Philippe; Peulen, Olivier; Castronovo, Vincenzo; Bellahcène, Akeila

doi:10.1016/j.diabres.2019.01.002

Cited by 93 publications

(67 citation statements)

References 119 publications

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“…Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is a major precursor of the AGEs. MGO mainly reacts with the arginine residues and, to a much lesser extent, with lysine residues, to form MGO-derived AGEs [10,11]. Once AGEs are formed, these irreversible products interact with the receptors for AGEs (RAGE) resulting in inflammation and the elevated production of reactive oxygen species (ROS), which are also closely linked to insulin resistance [12].…”

Section: Introductionmentioning

confidence: 99%

Psoralea corylifoliaL. Seed Extract Attenuates Methylglyoxal-Induced Insulin Resistance by Inhibition of Advanced Glycation End Product Formation

Truong

Seo

Jun

2019

Oxidative Medicine and Cellular Longevity

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Accumulation of advanced glycation end products (AGEs) in the body has been implicated in the pathogenesis of metabolic conditions, such as diabetes mellitus. Methylglyoxal (MGO), a major precursor of AGEs, has been reported to induce insulin resistance in both in vitro and in vivo studies. Psoralea corylifolia seeds (PCS) have been used as a traditional medicine for several diseases, but their potential application in treating insulin resistance has not yet been evaluated. This study is aimed at investigating whether PCS extract could attenuate insulin resistance induced by MGO. Male C57BL/6N mice (6 weeks old) were administered 1% MGO in their drinking water for 18 weeks, and the PCS extract (200 or 500 mg/kg) was orally administered daily from the first day of the MGO administration. We observed that both 200 and 500 mg/kg PCS extract treatment significantly improved glucose tolerance and insulin sensitivity and markedly restored p-Akt and p-IRS1/2 expression in the livers of the MGO-administered mice. Additionally, the PCS extract significantly increased the phosphorylation of Akt and IRS-1/2 and glucose uptake in MGO-treated HepG2 cells. Further studies showed that the PCS extract inhibited MGO-induced AGE formation in the HepG2 cells and in the sera of MGO-administered mice. PCS extract also increased the expression of glyoxalase 1 (GLO1) in the liver tissue of MGO-administered mice. The PCS extract significantly decreased the phosphorylation of ERK, p38, and NF-κB and suppressed the mRNA expression of proinflammatory molecules including TNF-α and IL-1β and iNOS in MGO-administered mice. Additionally, we demonstrated that the PCS extract attenuated oxidative stress, as evidenced by the reduced ROS production in the MGO-treated cells and the enhanced expression of antioxidant enzymes in the liver of MGO-administered mice. Thus, PCS extract ameliorated the MGO-induced insulin resistance in HepG2 cells and in mice by reducing oxidative stress via the inhibition of AGE formation. These findings suggest the potential of PCS extract as a candidate for the prevention and treatment of insulin resistance.

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Section: Introductionmentioning

confidence: 99%

Psoralea corylifoliaL. Seed Extract Attenuates Methylglyoxal-Induced Insulin Resistance by Inhibition of Advanced Glycation End Product Formation

Truong

Seo

Jun

2019

Oxidative Medicine and Cellular Longevity

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“…MG, a reactive intermediate of cellular metabolism, is the most potent precursor of advanced glycation end products and is strictly correlated with an increase in oxidative stress in AD [ 55 ]. Therefore, MG can be a useful tool for screening potential neuroprotective compounds that ameliorate oxidative stress [ 56 ]. Similarly, as in the study with the glucagon-like peptide 1 analog liraglutide, where liraglutide enhanced SH-SY5Y cell viability [ 57 ], PrRP31 and palm 11 -PrRP31 increased viability determined by the MTT test in the MG-stressed SH-SY5Y cells.…”

Section: Discussionmentioning

confidence: 99%

Cellular Signaling and Anti-Apoptotic Effects of Prolactin-Releasing Peptide and Its Analog on SH-SY5Y Cells

Zmeškalová

Popelová

Exnerová

et al. 2020

IJMS

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Prolactin-releasing peptide (PrRP), a natural ligand for the GPR10 receptor, is a neuropeptide with anorexigenic and antidiabetic properties. Due to its role in the regulation of food intake, PrRP is a potential drug for obesity treatment and associated type 2 diabetes mellitus (T2DM). Recently, the neuroprotective effects of lipidized PrRP analogs have been proven. In this study, we focused on the molecular mechanisms of action of natural PrRP31 and its lipidized analog palm11-PrRP31 in the human neuroblastoma cell line SH-SY5Y to describe their cellular signaling and possible anti-apoptotic properties. PrRP31 significantly upregulated the phosphoinositide-3 kinase-protein kinase B/Akt (PI3K-PKB/Akt) and extracellular signal-regulated kinase/cAMP response element-binding protein (ERK-CREB) signaling pathways that promote metabolic cell survival and growth. In addition, we proved via protein kinase inhibitors that activation of signaling pathways is mediated specifically by PrRP31 and its palmitoylated analog. Furthermore, the potential neuroprotective properties were studied through activation of anti-apoptotic pathways of PrRP31 and palm11-PrRP31 using the SH-SY5Y cell line and rat primary neuronal culture stressed with toxic methylglyoxal (MG). The results indicate increased viability of the cells treated with PrRP and palm11-PrRP31 and a reduced degree of apoptosis induced by MG, suggesting their potential use in the treatment of neurological disorders.

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“…Habár az inzulinkezelés megoldotta a diabetes akut problémáját, a hosszú távú szövődmények azóta is szedik áldozataikat; ezek leküzdése az inzulinkezeléshez hasonlatosan valódi áttörést jelentene. A diabeteses szövődmények és a hyperglykaemia közötti kapcsolat igazolt, hiszen a hyperglykaemia fokozott oxidatív és karbonilstresszel, nagyobb mértékű AGE-képződéssel jár együtt [2]. A jelen tanulmányban áttekintettük az AGE-k képződését, lehetséges szerepüket a szövődmények kialakulásában, és beszámoltunk a terápiás beavatkozás egy lehetséges új módjáról.…”

Section: Következtetésunclassified

“…Természetesen sokkoló, hogy 2017-ben mintegy 451 millió embertársunkat érintette ez a probléma [1]. Szintén megdöbbentő, hogy ugyanebben az évben közel 5 millióan közülük a diabetes miatt haltak meg [2]. A száraz adatok mögött milliónyi olyan ember van, aki a mindennapjait a súlyos szövődmények miatt erősen romlott minőségben éli.…”

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A karbonilstressz szerepe a diabetes szövődményeinek kialakulásában

Makk-Merczel

Szarka

2019

Orvosi Hetilap

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The relationship between the potentially developing complications of the 451 million people affected by diabetes and hyperglycaemia can be based on the enhanced generation of advanced glycation endproducts and the more intensive oxidative and carbonyl stress. Advanced glycation endproducts generated partly due to carbonyl stress play an important role in the pathogenesis of diabetic complications such as elevated arterial thickness, vascular permeability, enhanced angiogenesis or the more rigid vessels induced nephropathy, neuropathy, retinopathy. Furthermore, the elevated thrombocyte aggregation, the reduced fibrinolysis induced elevated coagulation, and the atherosclerosis or the mitochondrial dysfunction are important as well. The most potent target of both the non-oxidative and oxidative generation of advanced glycation endproducts can be the scavenging of α,β-unsaturated aldehydes. Although, aminoguanidine, the prototype of scavenger molecules, showed protection in different animal models, it failed in the human clinical studies. Finally, the clinical studies were terminated almost 20 years ago. The endogen dipeptide L-carnosine was also expected to mitigate the complications due to carbonyl stress. However, its clinical significance was limited by the serum carnosinases and by the consequent low serum stability and bioavailability. The carnosinase resistance of the molecule can be achieved by the change of the carboxyl group of the molecule to hydroxyl group. At the same time, the biosafety and the carbonyl stress scavenging activity of the molecule could be preserved. Although clinical studies could not be performed in the last six months, on the basis of the in vitro and in vivo results, carnosinole seems to be a promising compound to mitigate and prevent the diabetic complications. Thus it is worth to the attention of the clinicians. Orv Hetil. 2019; 160(40): 1567–1573.

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Methylglyoxal, a potent inducer of AGEs, connects between diabetes and cancer

Cited by 93 publications

References 119 publications

Psoralea corylifoliaL. Seed Extract Attenuates Methylglyoxal-Induced Insulin Resistance by Inhibition of Advanced Glycation End Product Formation

Psoralea corylifoliaL. Seed Extract Attenuates Methylglyoxal-Induced Insulin Resistance by Inhibition of Advanced Glycation End Product Formation

Cellular Signaling and Anti-Apoptotic Effects of Prolactin-Releasing Peptide and Its Analog on SH-SY5Y Cells

A karbonilstressz szerepe a diabetes szövődményeinek kialakulásában

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