Glyoxalase 1 Modulation in Obesity and Diabetes

Rabbani, Naila; Thornalley, Paul J.

doi:10.1089/ars.2017.7424

Cited by 69 publications

(81 citation statements)

References 200 publications

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“…However, there is need to devise novel approaches to lower AGEs by harnessing the endogenous defenses in place, which are likely to prevent AGE formation and potentially pose fewer side effects. In a recent promising clinical trial, a combination therapy of trans-Resveratrol (tRes) and Hesperetin (HESP) helped improve glycemic control and vascular inflammation in healthy overweight and obese individuals via induction of Glo1 (Rabbani and Thornalley, 2018b). This suggests that inhibition of MGO accumulation via induction of glyoxalases could be a potential therapeutic strategy for glycation-mediated diseases.…”

Section: Glyoxalases As a Target For Therapymentioning

confidence: 99%

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

et al. 2018

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Accumulation of advanced glycation end products (AGEs) on nucleotides, lipids, and peptides/proteins are an inevitable component of the aging process in all eukaryotic organisms, including humans. To date, a substantial body of evidence shows that AGEs and their functionally compromised adducts are linked to and perhaps responsible for changes seen during aging and for the development of many age-related morbidities. However, much remains to be learned about the biology of AGE formation, causal nature of these associations, and whether new interventions might be developed that will prevent or reduce the negative impact of AGEs-related damage. To facilitate achieving these latter ends, we show how invertebrate models, notably Drosophila melanogaster and Caenorhabditis elegans, can be used to explore AGE-related pathways in depth and to identify and assess drugs that will mitigate against the detrimental effects of AGE-adduct development.

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Section: Glyoxalases As a Target For Therapymentioning

confidence: 99%

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

et al. 2018

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“…Dicarbonyl metabolites can also contribute to the progression and development of diabetic kidney diseases. The tRES‐HESP formulation of resveratrol may therefore deliver glyoxalase‐1–mediated beneficial effects in such cases . Apart from the combination approach, administration of resveratrol, also showed significant impact on reducing the blood glucose level in overweight subjects …”

Section: Completed Clinical Trialsmentioning

confidence: 99%

“…90 It has been demonstrated that increased glyoxalase 1 expression slows down the progression of obesity and insulin resistance by alleviating dicarbonyl metabolites such as methylglyoxal. 91 A coformulation of trans-resveratrol and hesperetin (tRES-HESP) significantly increased the expression of glyoxalase 1 and decreased the plasma methylglyoxal and total body methylglyoxal-protein glycation in overweight subjects. 92 The coformulation also significantly decreased fasting and postprandial plasma glucose levels, and improved insulin sensitivity.…”

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confidence: 99%

“…The tRES-HESP formulation of resveratrol may therefore deliver glyoxalase-1-mediated beneficial effects in such cases. 91,93 Apart from the combination approach, administration of resveratrol, also showed significant impact on reducing the blood glucose level in overweight subjects. 68 A chronic low-grade inflammatory state is linked to obesity, diabetes, and MS. 94 Resveratrol has shown utility in the treatment of MS patients.…”

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confidence: 99%

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Health benefits of resveratrol: Evidence from clinical studies

Singh

Verma

et al. 2019

Medicinal Research Reviews

351

238

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Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. The molecular basis for the pleiotropic activities of resveratrol are based on its ability to modulate multiple cell signaling molecules such as cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor‐κB, Notch, 5′‐AMP‐activated protein kinase, intercellular adhesion molecule, vascular cell adhesion molecule, sirtuin type 1, peroxisome proliferator‐activated receptor‐γ coactivator 1α, insulin‐like growth factor 1, insulin‐like growth factor‐binding protein 3, Ras association domain family 1α, pAkt, vascular endothelial growth factor, cyclooxygenase 2, nuclear factor erythroid 2 like 2, and Kelch‐like ECH–associated protein 1. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed.

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“…MG is detoxified by enzymes glyoxalase 1 and 2 (Glo1, Glo2) to D-lactate (in contrast to Llactate, the end product of glycolysis), which can be measured in peripheral blood, and serves as a surrogate marker of whole-body MG production (19). Previously, we demonstrated that nine days of an isocaloric fructose-restricted diet reduced available substrate for DNL and resultant liver fat in children with obesity and metabolic syndrome who identified as high habitual sugar consumers (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Isocaloric Fructose Restriction Reduces Serum d-Lactate Concentration in Children With Obesity and Metabolic Syndrome

Erkin-Cakmak

Bains

Caccavello

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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Objective: To investigate the link between dietary sugar consumption and two separate pathogenetic mechanisms associated with metabolic syndrome: de novo lipogenesis (DNL) and non-enzymatic glycation. Design and participants: We assessed changes in serum D-lactate (the detoxification endproduct of methylglyoxal) concentration in response to nine days of isocaloric fructose restriction in 20 children with obesity and metabolic syndrome, and examined correlations with changes in DNL, liver fat, insulin sensitivity and other metrics of hepatic metabolism. Interventions: Nine days of dietary sugar restriction, with substitution of equal amounts of refined starch. Main Outcome Measures: On day 0 and 10, children had lab evaluation of D-lactate levels and other analytes, and underwent oral glucose tolerance testing, magnetic resonance spectroscopy to quantify fat depots, and 13 C-acetate incorporation into triglyceride to measure DNL. Results: D-lactate was associated with baseline liver fat fraction (p<0.001) and visceral adipose tissue (p<0.001), but not with subcutaneous adipose tissue. At baseline, D-lactate was positively correlated with DNL-AUC (p=0.003), liver fat fraction (p=0.02), triglyceride (p=0.004) and triglyceride to HDL ratio (p=0.002). After nine days of isocaloric fructose restriction, serum Dlactate levels reduced by 50% (p<0.0001), and changes in D-lactate correlated with both changes in DNL-AUC, and measures of insulin sensitivity. Conclusion: Baseline correlation of D-lactate with DNL and measures of insulin sensitivity; and reduction in D-lactate following nine days of isocaloric fructose restriction suggest that DNL and non-enzymatic glycation are functionally linked via intermediary glycolysis in the pathogenesis

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Glyoxalase 1 Modulation in Obesity and Diabetes

Abstract: Glo1 inducers may now be evaluated in Phase 2 clinical trials for treatment of NAFLD and vascular complications of diabetes. Antioxid. Redox Signal. 00, 000-000.

Cited by 69 publications

References 200 publications

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

Health benefits of resveratrol: Evidence from clinical studies

Isocaloric Fructose Restriction Reduces Serum d-Lactate Concentration in Children With Obesity and Metabolic Syndrome

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