Developmental exposure to DEHP alters hepatic glucose uptake and transcriptional regulation of GLUT2 in rat male offspring

Rajagopal, Gokulapriya; Bhaskaran, Ravi Sankar; Balasubramanian, K.

doi:10.1016/j.tox.2018.12.004

Cited by 24 publications

(20 citation statements)

References 41 publications

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“…As shown in Figure 2, phosphorylation of Akt Ser473 and phosphorylation of GSK‐3α/β were upregulated in RG‐treated group compared with HFD‐Veh group. Additionally, the disorder of glucose uptake could partly contribute to hyperglycemia, and the expression levels of Glut2 in liver directly reflect the degree of glucose uptake (Rajagopal, Bhaskaran, & Karundevi, 2019). In this study, western blot experiments revealed that RG administration dose‐dependently elevated the protein expression of Glut2 compared to HFD‐Veh group in the tissue of liver (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

Riligustilide alleviates hepatic insulin resistance and gluconeogenesis in T2DM mice through multitarget actions

Guan

et al. 2021

Phytotherapy Research

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Riligustilide (RG), one of the dimeric phthalides of Angelica sinensis and Ligusticum chuanxiong, was confirmed effective against many diseases. However, its effects on type 2 diabetes mellitus (T2DM) and the underlying molecular mechanisms have not been clearly elucidated yet. The current study was designed to investigate the hypoglycemic potential by which RG affects the pathogenesis of T2DM. Comprehensive insights into the effects and underlying molecular mechanisms of RG on attenuating aberrant metabolism of glucose were determined in high‐fat diet‐induced T2DM mice and insulin‐resistant (IR) HepG2 cells. In high‐fat diet‐induced C57BL/6J mice, RG administration significantly reduced hyperglycemia, decreased hyperinsulinemia, and ameliorated glucose intolerance. Mechanistically, RG activated PPARγ and insulin signaling pathway to improve insulin sensitivity, and increase glucose uptake as well as glycogenesis. In addition, RG also upregulated AMPK‐TORC2‐FoxO1 axis to attenuate gluconeogenesis in vivo and in vitro. According to the findings, RG may be a promising candidate for the treatment of T2DM.

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Section: Resultsmentioning

confidence: 99%

Riligustilide alleviates hepatic insulin resistance and gluconeogenesis in T2DM mice through multitarget actions

Guan

et al. 2021

Phytotherapy Research

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“…Many findings provided strong evidence that DEHP hurt the mammalian liver system. Research revealed that DEHP exposure changes glucose intake and transcription of solute carrier family 2 member 2 (GLUT2) in the liver of rats . It is confirmed that DEHP decreased the lipid hydrolysis and accelerated triglyceride accumulation in the liver, which causes the imbalance of lipid metabolism .…”

Section: Discussionmentioning

confidence: 99%

“…Research revealed that DEHP exposure changes glucose intake and transcription of solute carrier family 2 member 2 (GLUT2) in the liver of rats. 40 It is confirmed that DEHP decreased the lipid hydrolysis and accelerated triglyceride accumulation in the liver, which causes the imbalance of lipid metabolism. 41 LYC, a red plant pigment found in tomatoes, watermelons, etc., 34 has been proved to be effective in antioxidant, anti-inflammatory, and antiobesity bioactivities.…”

Section: ■ Discussionmentioning

confidence: 99%

Lycopene Prevents DEHP-Induced Liver Lipid Metabolism Disorder by Inhibiting the HIF-1α-Induced PPARα/PPARγ/FXR/LXR System

Zhao

Wang³

et al. 2020

J. Agric. Food Chem.

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phthalate (DEHP) is a widespread pollutant that badly affects animals and human health. Lycopene (LYC) has been used as a dietary supplement that has effective antioxidant and antiobesity functions. The present goal was to understand the molecular mechanisms of LYC preventing DEHP-induced lipid metabolism of the liver. The mice were intragastrically administered with LYC (5 mg/kg) and/or DEHP (500 mg/kg or 1000 mg/kg). Here, we found that LYC attenuated DEHP-caused hepatic histopathological lesions including steatosis. Hematological and biochemical analyses revealed that LYC ameliorated DEHP-caused liver function and lipid metabolism disorders. DEHP caused lipid metabolism disorders via activating the peroxisome proliferator activated receptor α/γ (PPARα/γ) signal transducer and Farnesoid X receptor (FXR)/liver X receptor (LXR) signaling pathway. As a major regulator of lipid metabolism, hypoxia-inducible factor-1α (HIF-1α) system was elevated with increased fatty degeneration under DEHP exposure. However, LYC could decrease the levels of HIF-1α/PPARα/PPARγ/FXR/LXR signaling pathway-related factors. Our research indicated that LYC could prevent DEHP-induced lipid metabolism disorders via inhibiting the HIF-1α-mediated PPARα/PPARγ/FXR/LXR system. This study may provide a possible molecular mechanism for fatty liver induced by DEHP.

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“…The phthalate monoester MEHP binds PPARγ similar to Rosiglitazone, an antidiabetic drug in the thiazolidinedione (TZD) class, but this binding induces the recruitment of only a subset of coregulators activating a subset of target genes with adipogenic effect [52,53]. Recent studies have shown that DEHP is able to interfere with the insulin signal suggesting DEHP exposure impairs insulin signal transduction and alters glucoregulatory events leading to the development of type 2 diabetes in F1 male offspring [56,57].…”

Section: Disrupting Action Of Dehp and Bpamentioning

confidence: 99%

Assessment of Exposure to Di-(2-ethylhexyl) Phthalate (DEHP) Metabolites and Bisphenol A (BPA) and Its Importance for the Prevention of Cardiometabolic Diseases

2022

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Exposomics analyses have highlighted the importance of biomonitoring of human exposure to pollutants, even non-persistent, for the prevention of non-communicable diseases such as obesity, diabetes, non-alcoholic fatty liver disease, atherosclerosis, and cardiovascular diseases. Phthalates and bisphenol A (BPA) are endocrine disrupting chemicals (EDCs) widely used in industry and in a large range of daily life products that increase the risk of endocrine and cardiometabolic diseases especially if the exposure starts during childhood. Thus, biomonitoring of exposure to these compounds is important not only in adulthood but also in childhood. This was the goal of the LIFE-PERSUADED project that measured the exposure to phthalates (DEHP metabolites, MEHP, MEHHP, MEOHP) and BPA in Italian mother–children couples of different ages. In this paper we describe the method that was set up for the LIFE PERSUADED project and validated during the proficiency test (ICI/EQUAS) showing that accurate determination of urinary phthalates and BPA can be achieved starting from small sample size (0.5 mL) using two MS techniques applied in cascade on the same deconjugated matrix.

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Developmental exposure to DEHP alters hepatic glucose uptake and transcriptional regulation of GLUT2 in rat male offspring

Cited by 24 publications

References 41 publications

Riligustilide alleviates hepatic insulin resistance and gluconeogenesis in T2DM mice through multitarget actions

Riligustilide alleviates hepatic insulin resistance and gluconeogenesis in T2DM mice through multitarget actions

Lycopene Prevents DEHP-Induced Liver Lipid Metabolism Disorder by Inhibiting the HIF-1α-Induced PPARα/PPARγ/FXR/LXR System

Assessment of Exposure to Di-(2-ethylhexyl) Phthalate (DEHP) Metabolites and Bisphenol A (BPA) and Its Importance for the Prevention of Cardiometabolic Diseases

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