Dual regulation of TxNIP by ChREBP and FoxO1 in liver

Noblet, Bénédicte; Benhamed, Fadila; O-Sullivan, InSug; Zhang, Wenwei; Filhoulaud, Gaëlle; Montagner, Alexandra; Polizzi, Arnaud; Marmier, Solenne; Burnol, Anne-Françoise; Guilmeau, Sandra; Issad, Tarik; Guillou, Hervé; Bernard, Catherine; Unterman, Terry G.; Postic, Catherine

doi:10.1016/j.isci.2021.102218

Cited by 14 publications

(8 citation statements)

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“…TXNIP affects the homeostasis of myocardial cells under ischemic stress by regulating redox status [52] . The study found that CD44 and TGF-β1 Participate in the development of diabetes nephropathy and liver brosis [53][54][55][56] . The pathogenesis of heart diseases is related to the activation of cardiac broblasts.…”

Section: Discussionmentioning

confidence: 99%

Explore the possible pathway of improving liver and heart injury in diabetes nephropathy based on bioinformatics analysis

Yang

Wang

et al. 2023

Preprint

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Background This study explore the possible pathway of MicroRNA-130a, TXNIP, CD44 and TGF-β1 improving liver and heart injury in diabetes nephropathy based on bioinformatics ananlysis.Methods Screening Key Genes Using Bioinformatics Analysis. The biochemical index and serum levels of MicroRNA-130a, TXNIP, CD44 and TGF-β1 were detected and analyzed by Pearson correlation analysis in 100 DN patients and 50 healthy controls. The rats model were randomly divided into two groups. The expression of MicroRNA-130a, TXNIP, CD44 and TGF-β1 in liver and heart and the morphological changes was detected.Results Screening and Analysis of Differentially Expressed Genes MicroRNA-130a and TXNIP, CD44 and TGFBI Involved in diabetes Nephropathy by Bioinformatics Methods. Compared to healthy controls, serum levels of MicroRNA-130a were decreased, while levels of TXNIP, CD44 and TGF-β1 were elevated in DN patients. Moreover, MicroRNA-130a was negatively correlated with TXNIP, CD44 and TGF-β1. In DN rats, the levels of TXNIP, CD44 and TGF-β1 in the liver and heart tissues were significantly elevated, while MicroRNA-130a levels were significantly decreased, compared to the NC group.Conclusion Upregulate MicroRNA-130a and decrease TXNIP, CD44 and TGF-β1 may participate in liver and heart injury pathway of diabetes nephropathy.

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Section: Discussionmentioning

confidence: 99%

Explore the possible pathway of improving liver and heart injury in diabetes nephropathy based on bioinformatics analysis

Yang

Wang

et al. 2023

Preprint

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“…This factor was upregulated in the mouse intestine during chronic consumption of high-fructose diet and elevated expression of GLUT5 [ 70 ]. There is a study suggesting that Txnip promotes the nuclear translocation of ChREBP factor, enhancing its binding to the promoter region of Slc2a5 gene due to the presence of two carbohydrate response elements (ChoRE) for binding of ChREBP [ 71 ], as well as influences methylation of the Slc2a5 gene [ 68 ]. ChREBP via ChoRE also regulates the expression of other genes encoding enzymes involved in fructose metabolism, such as ketohexokinase (KHK), which intensifies fructose metabolism-increasing hepatic lipogenesis [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Phenolics-Rich Extracts of Dietary Plants as Regulators of Fructose Uptake in Caco-2 Cells via GLUT5 Involvement

et al. 2021

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The latest data link the chronic consumption of large amounts of fructose present in food with the generation of hypertension and disturbances in carbohydrate and lipid metabolism, which promote the development of obesity, non-alcoholic fatty liver disease, insulin resistance, and type 2 diabetes. This effect is possible after fructose is absorbed by the small intestine cells and, to a lesser extent, by hepatocytes. Fructose transport is dependent on proteins from the family of glucose transporters (GLUTs), among which GLUT5 selectively absorbs fructose from the intestine. In this study, we examined the effect of four phenolic-rich extracts obtained from A. graveolens, B. juncea, and M. chamomilla on fructose uptake by Caco-2 cells. Extracts from B. juncea and M. chamomilla most effectively reduced fluorescent fructose analogue (NBDF) accumulation in Caco-2, as well as downregulated GLUT5 protein levels. These preparations were able to decrease the mRNA level of genes encoding transcription factors regulating GLUT5 expression-thioredoxin-interacting protein (TXNIP) and carbohydrate-responsive element-binding protein (ChREBP). Active extracts contained large amounts of apigenin and flavonols. The molecular docking simulation suggested that some of identified phenolic constituents can play an important role in the inhibition of GLUT5-mediated fructose transport.

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“…Interestingly, TXNIP itself is a key regulator of hepatic glucose production, and gene silencing of hepatic TXNIP caused fasting hypoglycaemia and evoked a decreased response to glucagon 68 . Additionally, suppression of TXNIP expression in the liver of diabetic db/db mice was sufficient to control hyperglycaemia, along with normalized expression of key genes that promote hepatic gluconeogenesis 69 . The effects of TXNIP on hepatic glucose production have been linked to the modulatory effects of TXNIP on the cellular redox system, which is known to control gluconeogenesis 70,71 .…”

Section: Discussionmentioning

confidence: 99%

Antidiabetic effects of quercetin and liraglutide combination through modulation of TXNIP/IRS‐1/PI3K pathway

Eraky

Ramadan

El-Magd

2021

Cell Biochemistry & Function

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The study was designed to assess the possible augmented antidiabetic effects of combining quercetin and liraglutide in a type 1 diabetes model, with emphasis on the contribution of hepatic thioredoxin interacting protein (TXNIP)/insulin receptor substrate 1 (IRS‐1)/phosphatidyl inositol‐3 kinase (PI3K) pathway. The wound‐healing effects were also examined. Diabetes was induced by a single i.p STZ injection (55 mg/kg). Diabetic rats were treated with either quercetin (100 mg/kg/day, orally) or liraglutide (0.3 mg/kg/twice daily, S.C.) or their combination. Drugs were also applied topically on the wound. Blood glucose levels, serum albumin, total protein, total cholesterol and triglycerides were measured. Histopathological examination of the liver, pancreas and skin tissues was performed using haematoxylin and eosin staining. The hepatic malondialdehyde level was measured spectrophotometrically. Hepatic TXNIP and PI3K levels were measured by enzyme‐linked immunsorbent assay (ELISA). Tissue expression of IRS‐1 and phospho‐IRS‐1 (Ser 616) was assessed by immunohistochemistry. Quercetin, liraglutide and their combination effectively decreased blood glucose levels, improved lipid profile, upregulated albumin and total protein serum levels and reduced hepatic oxidative stress with the combination being most effective. Moreover, the combination group showed enhanced wound‐healing effects and almost normalized hepatic and pancreatic histopathology. Quercetin and/or liraglutide significantly decreased TXNIP levels and serine phosphorylation of IRS‐1 and increased PI3K levels compared to the diabetic untreated group. Interestingly, only the combination therapy normalized hepatic IRS‐1 expression. The combination of quercetin and liraglutide showed enhanced antidiabetic effects, possibly through lowering hepatic TXNIP levels, with the resultant up‐regulation of the IRS‐1/PI3K pathway.

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Dual regulation of TxNIP by ChREBP and FoxO1 in liver

Cited by 14 publications

References 50 publications

Explore the possible pathway of improving liver and heart injury in diabetes nephropathy based on bioinformatics analysis

Explore the possible pathway of improving liver and heart injury in diabetes nephropathy based on bioinformatics analysis

Phenolics-Rich Extracts of Dietary Plants as Regulators of Fructose Uptake in Caco-2 Cells via GLUT5 Involvement

Antidiabetic effects of quercetin and liraglutide combination through modulation of TXNIP/IRS‐1/PI3K pathway

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