Metabolomics-Based Prospective Studies and Prediction of Type 2 Diabetes Mellitus Risks

Satheesh, Gopika; Ramachandran, Surya; Jaleel, Abdul

doi:10.1089/met.2019.0047

Cited by 24 publications

(13 citation statements)

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“…The increasing data have revealed a close link between obesity, T2D, oxidative stress, and mitochondrial dysfunction [79,80]. First of all, it is important to specify that ROS are oxygen-derived molecules essentially produced by NO • , NADPH oxidase, and mitochondria in response to bacterial invasion or cytokines [81].…”

Section: Effects Of Phytosterols On Oxidative Stressmentioning

confidence: 99%

Phytosterols: Nutritional Health Players in the Management of Obesity and Its Related Disorders

et al. 2020

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Obesity and its related disorders, such as diabetes and cardiovascular risk, represent an emerging global health issue. Even though genetic factors seem to be the primary actors in the development and progression of these diseases, dietary choices also appear to be of crucial importance. A healthy diet combined with physical activity have been shown to ameliorate glycaemic levels and insulin sensitivity, reduce body weight and the risk of chronic diseases, and contribute to an overall improvement in quality of life. Among nutrients, phytosterols have become the focus of growing attention as novel functional foods in the management of metabolic disorders. Phytosterols are natural plant compounds belonging to the triterpene family and are structurally similar to cholesterol. They are known for their cholesterol-lowering effects, anti-inflammatory and antioxidant properties, and the benefits they offer to the immune system. The present review aims to provide an overview of these bioactive compounds and their therapeutic potential in the fields of obesity and metabolic disorders, with special attention given to oxidative stress, inflammatory status, and gut dysbiosis, all common features of the aforementioned diseases.

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Section: Effects Of Phytosterols On Oxidative Stressmentioning

confidence: 99%

Phytosterols: Nutritional Health Players in the Management of Obesity and Its Related Disorders

et al. 2020

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“…Moreover, the parallel high level of blood glucose and (or) low insulin conditions, ultimately, might have serious injurious consequences on the body physiology (Hoybergs et al, 2008). Therefore, DM is a major threat to public health and its prevalence is increasing as this disease can cause long-lasting impairments of physiological functions and failures in organs with widespread impediments (Meo et al, 2015;Satheesh et al, 2020). For instance, 40% of end stage renal disease (ESRD) cases in diabetic patients because of diabetic nephropathy (Kundu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Sinapic Acid Ameliorates the Progression of Streptozotocin (STZ)-Induced Diabetic Nephropathy in Rats via NRF2/HO-1 Mediated Pathways

Alaofi

2020

Front. Pharmacol.

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Diabetic neuropathy (DN) is a complicated inauspicious outcome of diabetes, like other abnormalities of diabetes the cause of DN is still vague and it may be the result of various pathological conditions leading up to end-stage renal failure. The present study examines the efficacy of sinapic acid (SA) in streptozotocin (STZ)-induced DN nephropathy and the linked pathway. Twenty-four rats were equally divided randomly into four categories: Normal control (NC), STZ, STZ + SA 20 mg/kg bw, and STZ + SA 40 mg/kg bw. After 8 weeks they were evaluated for ratio of renal index, the fasting blood glucose (FBG), blood urea nitrogen (BUN), 24 h urea protein, serum creatinine (SCr), reduced glutathione peroxidase (GPx), superoxide dismutase (SOD), lipid peroxidation (MDA), tumor necrosis factor a (TNFa), interleukin (IL)-6, as well as lipid profile total cholesterol (TC), total triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) levels. Additionally, histomorphology and ultrastructure of the kidneys were also assessed. Protein expression levels of transforming growth factor-b1 (TGF-b1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), IkBa protein (IkBa), anti-apoptotic protein BCl2, nuclear factor kappa B (NF-kB), and Bax were examined. We observed that SA 20 mg/kg bw and 40 mg/kg bw pretreatment significantly and dose-dependently upregulated the protein expression of HO-1, Nrf2, IKBa, and Bcl-2 but downregulated the protein expression of NF-kB, proposing that the nephroprotective mechanism of SA is due to its antioxidant and anti-inflammatory activity; SA prevents the release of cytokines and inflammatory markers (TNFa and IL-6), upregulates antioxidant defense enzymes, and reduces lipid peroxidation, as well as nitric oxide, and anti-apoptotic activity, which may be influenced by the regulation of TNF-a, IL-6, Bcl-2, NF-kB, and BaX via the Nrf2/HO-1 pathway in STZ induced DN. Thus, our results suggest that SA ameliorates the development of STZ-induced DN in rats via NRF2/HO-1 mediated pathways. Further comprehensive studies are required for complete elucidation of the fundamental mechanisms.

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“…We also checked metabolomicsbased studies of T2DM and the Human Metabolome Database for these metabolites [39]. We found that glucose, hypoxanthine, alanine, aspartate, galactose, hyaluronate, and methylglyoxal levels have been reported to be associated with T2DM [32,39,40]. These metabolite markers can be used for further empirical investigation to verify their prognostic and diagnostic values in insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

In Silico Metabolic Modeling Reveals Muscle Metabolite Markers of Insulin Resistance In Newly Diagnosed Diabetic Patients

Khoshnejat

Banaei-Moghaddam

Kavousi

et al. 2020

Preprint

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BackgroundType 2 diabetes mellitus (T2DM) is a challenging and globally ubiquitous metabolic disease caused by insulin resistance. Skeletal muscle is the major insulin-sensitive tissue that plays a great role in blood sugar homeostasis. Dysfunction of muscle metabolism is implicated in the disturbance of glucose hemostasis and the development of insulin resistance and T2DM. Here, we attempted to find metabolic dysregulations that are associated with the onset of T2DM. Besides, metabolite markers of T2DM were explored. ResultsWe reconstructed a human muscle-specific metabolic model and applied it to perform metabolic analysis in newly diagnosed T2DM patients. We investigated the metabolism reprogramming by using two topology-based and constraint-based approach. Our results showed that metabolic alterations have occurred in carbohydrate, fatty acids, lipids, amino acids, and inositol phosphate metabolisms as well as pathways implicated in building extracellular matrix (ECM). Also, dysregulation of coenzyme Q10 metabolism was observed. Moreover, we applied a machine learning method to predict potential metabolite markers of insulin resistance in muscle. 13 exchange metabolites were predicted as the potential metabolite markers of insulin resistance in skeletal muscle. The efficiency of these markers in detecting insulin-resistant muscle was validated using a separate muscle gene expression data from another diabetes-related study. ConclusionIn this study, the most updated muscle-specific metabolic model was generated and successfully was validated. This model was used for the investigation of metabolic disturbances at the onset of T2DM. Our results indicated the significance of ECM metabolites in insulin resistance, and reinforce the role of coenzyme Q10 as a candidate for further research in insulin resistance and T2DM treatment. The model is freely available and can be used for other muscle metabolic studies.

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Metabolomics-Based Prospective Studies and Prediction of Type 2 Diabetes Mellitus Risks

Cited by 24 publications

References 81 publications

Phytosterols: Nutritional Health Players in the Management of Obesity and Its Related Disorders

Phytosterols: Nutritional Health Players in the Management of Obesity and Its Related Disorders

Sinapic Acid Ameliorates the Progression of Streptozotocin (STZ)-Induced Diabetic Nephropathy in Rats via NRF2/HO-1 Mediated Pathways

In Silico Metabolic Modeling Reveals Muscle Metabolite Markers of Insulin Resistance In Newly Diagnosed Diabetic Patients

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