Non-alcoholic fatty liver disease, insulin resistance, metabolic syndrome and their association with vascular risk

Metabolism, Journal Year: 2021, Volume and Issue: 119, P. 154770 - 154770

Published: April 15, 2021

Language: Английский

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Kynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target?

Cells, Journal Year: 2023, Volume and Issue: 12(3), P. 460 - 460

Published: Jan. 31, 2023

The tryptophan–kynurenine pathway (Trp–KYN) is the major route for tryptophan conversion in brain and periphery. Kynurenines display a wide range of biological actions (which are often contrasting) such as cytotoxic/cytoprotective, oxidant/antioxidant or pro-/anti-inflammatory. net effect depends on their local concentration, cellular environment, well complex positive negative feedback loops. imbalance between beneficial harmful kynurenines was implicated pathogenesis various neurodegenerative disorders, psychiatric illnesses metabolic including diabetes mellitus (DM). Despite available therapies, DM may lead to serious macro- microvascular complications cardio- cerebrovascular disease, peripheral vascular chronic renal diabetic retinopathy, autonomic neuropathy cognitive impairment. It established that low-grade inflammation, which coincides with DM, can affect function KP and, conversely, modulate immune response. This review provides detailed summary findings concerning status Trp–KYN based animal, human microbiome studies. We highlight importance molecular interplay deranged (functionally qualitatively) Trp development insulin resistance. emerges novel target search preventive therapeutic interventions DM.

Language: Английский

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Diabetes and restenosis

Cardiovascular Diabetology, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 14, 2022

Restenosis, defined as the re-narrowing of an arterial lumen after revascularization, represents increasingly important issue in clinical practice. Indeed, number stent placements has risen to estimate that exceeds 3 million annually worldwide, revascularization procedures have become much more common. Several investigators demonstrated vessels patients with diabetes mellitus increased risk restenosis. Here we present a systematic overview effects on in-stent Current classification and updated epidemiology restenosis are discussed, alongside main mechanisms underlying pathophysiology this event. Then, summarize presentation restenosis, emphasizing importance glycemic control diabetic patients. who underwent proper remains imperative.

Language: Английский

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Role of Impaired Glycolysis in Perturbations of Amino Acid Metabolism in Diabetes Mellitus

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1724 - 1724

Published: Jan. 15, 2023

The most frequent alterations in plasma amino acid concentrations type 1 and 2 diabetes are decreased L-serine increased branched-chain (BCAA; valine, leucine, isoleucine) levels. likely cause of deficiency is synthesis 3-phosphoglycerate, the main endogenous precursor L-serine, due to impaired glycolysis. BCAA levels increase supply pyruvate oxaloacetate from glycolysis, enhanced NADH + H+ beta-oxidation, subsequent decrease flux through citric cycle muscles. These α-ketoglutarate for transamination activity keto dehydrogenase, rate-limiting enzyme catabolism. contributes phospholipids deoxysphinganines, which play a role diabetic neuropathy, homocysteine disposal, glycine deficiency. Enhanced contribute aromatic acids (phenylalanine, tyrosine, tryptophan), insulin resistance, accumulation various metabolites, whose influence on progression not clear. It concluded that should be monitored patients with diabetes, systematic investigation needed examine effects supplementation when these decreased.

Language: Английский

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Intended and Unintended Benefits of Folic Acid Fortification—A Narrative Review

Foods, Journal Year: 2023, Volume and Issue: 12(8), P. 1612 - 1612

Published: April 11, 2023

Inadequate folate intake during pregnancy is the leading cause of development neural tube defects (NTDs) in newborns. For this reason, mandatory fortification folic acid, a synthetic, easily bioavailable form, processed cereals and cereal products has been implemented US since 1 January 1998 to reduce risk NTD newborn children. This report aimed review literature related impact mandated acid on intended unintended benefits health. Potential adverse effects were also discussed. We searched Pubmed, Google Scholar, Embase, SCOPUS, Cochrane databases for reports. About 60 reports published between December 2022 reviewed, summarized, served as background review. The benefit was decreased prevalence NTDs, while reduction anemia, blood serum homocysteine, developing cardiovascular diseases. issues with are presence unmetabolized circulation, increased cancer, masking vitamin B-12 deficiency. From health perspective, it important monitor periodically.

Language: Английский

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Mapping the metabolic reprogramming induced by sodium-glucose cotransporter 2 inhibition

JCI Insight, Journal Year: 2023, Volume and Issue: 8(7)

Published: Feb. 21, 2023

Diabetes is associated with increased risk for kidney disease, heart failure, and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) prevent these adverse outcomes; however, the mechanisms involved are not clear. We generated a roadmap of metabolic alterations that occur in different organs diabetes response to SGLT2i. In vivo labeling 13C-glucose normoglycemic diabetic mice treated or without dapagliflozin, followed by metabolomics flux analyses, showed that, diabetes, glycolysis glucose oxidation impaired kidney, liver, heart. Treatment dapagliflozin failed rescue glycolysis. SGLT2 inhibition all organs; this was modulation redox state. altered methionine cycle metabolism, evident decreased betaine levels, whereas treatment SGLT2i hepatic along homocysteine levels. mTORC1 activity inhibited stimulation AMPK both animals, possibly explaining protective effects against diseases. Collectively, our findings suggest induces reprogramming orchestrated AMPK-mTORC1 signaling common distinct various tissues, implications aging.

Language: Английский

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N‐homocysteinylation of DJ‐1 promotes neurodegeneration in Parkinson's disease

Aging Cell, Journal Year: 2024, Volume and Issue: 23(5)

Published: Feb. 21, 2024

DJ-1, also known as Parkinson's disease protein 7 (Park7), is a multifunctional that regulates oxidative stress and mitochondrial function. Dysfunction of DJ-1 implicated in the pathogenesis (PD). Hyperhomocysteinemia associated with an increased risk PD. Here we show homocysteine thiolactone (HTL), reactive thioester (Hcy), covalently modifies on lysine 182 (K182) residue age-dependent manner. The N-homocysteinylation (N-hcy) abolishes its neuroprotective effect against dysfunction, exacerbating cell toxicity. Blocking N-hcy restores protective effect. These results indicate promotes progression Inhibiting may exert

Language: Английский

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The effect of diet-induced weight loss on circulating homocysteine levels in people with obesity and type 2 diabetes

Nutrition Journal, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 3, 2024

Abstract Background/aims Having type 2 diabetes (T2D) in combination with being overweight results an additional increase cardiovascular disease (CVD) risk. In addition, T2D and obesity are associated increased levels of total homocysteine (tHcy), possibly contributing to the CVD Weight loss dieting has positive effects on several risk factors, but whether it affects tHcy remains unclear. Therefore, aim this study was determine effect a calorie restricted diet people T2D. Methods post-hoc analysis POWER study, adults BMI greater than 27 kg/m² were included from outpatient clinic Erasmus Medical Center, Rotterdam. The patients subjected very low-calorie fortified meal replacements for 20 weeks. Before after intervention, blood samples collected measure other factors like glycaemic lipid parameters. Results 161 participants included, mean age 54 years (range 26–74), weight 104.6 ± 19.9 kg HbA1c 62.7 14.3 mmol/mol. At baseline, men displayed higher women, level positively correlated body triglyceride levels, while negatively renal function HDL cholesterol. During bodyweight reduced by 9.7% (from 94.5 18.1 p < 0.001), all measured parameters improved significantly. However, remained unchanged 12.1 4.1 4.2 umol/L, = 0.880). change during intervention (p 0.01 0.008, respectively). People who lost 10 (n 92) had -0.47 more ≥ 69) 0.60 umol/L 0.021). Conclusion conclusion, our data show that does not affect obesity, despite use folic acid vitamin B12. Our showed negative correlation between loss, suggesting (> kg) tHcy. Future studies should explore potential induced target question if reduction strategies could be clinically beneficial.

Language: Английский

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Acute Antiplatelet Effects of an Oleocanthal-Rich Olive Oil in Type II Diabetic Patients: A Postprandial Study

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 908 - 908

Published: Jan. 11, 2024

Postprandial dysmetabolism is a common entity of type 2 diabetes mellitus (T2DM) and may act as daily stressor the already dysfunctional diabetic platelets. This study aims to investigate whether oleocanthal-rich olive oils (OO), incorporated into carbohydrate-rich meal, can affect postprandial platelet aggregation. Oleocanthal cyclooxygenase inhibitor with putative antiplatelet properties. In this randomized, single-blinded, crossover study, ten T2DM patients consumed five isocaloric meals containing 120 g white bread combined with: (i) 39 butter, (ii) butter 400 mg ibuprofen, (iii) 40 mL OO (phenolic content < 10 mg/Kg), (iv) 250 mg/Kg oleocanthal (v) 500 oleocanthal. Metabolic markers along ex vivo ADP- thrombin receptor-activating peptide (TRAP)-induced aggregation were measured before for 4 h after meals. The glycemic lipidemic response was similar between However, sustained (90-240 min) dose-dependent reduction in platelets' sensitivity both ADP (50-100%) TRAP (20-50%) observed comparison or effect comparable that ibuprofen meal. conclusion, consumption reduce activity during period, irrespective hyperglycemia lipidemia.

Language: Английский

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SAH is a major metabolic sensor mediating worsening metabolic crosstalk in metabolic syndrome

Redox Biology, Journal Year: 2024, Volume and Issue: 73, P. 103139 - 103139

Published: April 27, 2024

In this study, we observed worsening metabolic crosstalk in mouse models with concomitant disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and hyperglycemia human coronary artery disease by analyzing profiles. We found that HHcy is most sensitive to other disorders. To identify genes metabolites responsible for the crosstalk, examined mRNA levels of 324 Hcy, glucose-related lipid systems. Hcy-metabolites (Hcy, SAH SAM) LS-ESI-MS/MS 6 organs (heart, liver, brain, lung, spleen, kidney) from C57BL/6J mice. Through linear regression analysis gene levels, discovered SAH-responsive were changes all mediated Serine, Taurine, G3P. worsen glucose metabolism cause upper glycolysis activation lower suppression, indicative accumulation glucose/glycogen G3P, Serine synthesis inhibition, ATP depletion. Insufficient due negative correlation PHGDH concentration may inhibit folate cycle transsulfurarion pathway consequential reduced antioxidant power, including glutathione, taurine, NADPH, NAD+. Additionally, identified SAH-activated pathological TG loop consequence increased fatty acid (FA) uptake, FA β-oxidation Ac-CoA production along lysosomal damage. concluded responsive mediates mainly via genes, organ-specific Hcy determines reprogramming, SAH, acetyl-CoA, Taurine are critical mediating redox disturbance, hypomethylation hyperacetylation linking reprogramming syndrome.

Language: Английский

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