Fatty Liver and Insulin Resistance in the Liver-Specific Knockout Mice of Mitogen Inducible Gene-6

Lee, Eun-Ah; Kim, Hee-Youn; Lee, Jun Choul; Kim, Koon Soon; Jeong, Won Hoon; Kim, Ki Young; Ku, Bon Jeong; Rhee, Sang Dal

doi:10.1155/2016/1632061

Cited by 9 publications

(9 citation statements)

References 28 publications

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“…Moreover, it has been reported that ERRFI1 regulates cholesterol and glucose metabolism in the liver. Errfi1 liver-specific knockout in mice altered expression of lipid and glucose metabolism-related genes, resulting in increased blood cholesterol and fasting glucose levels and leading to insulin resistance [71][72][73]. In Fig.…”

Section: Discussionmentioning

confidence: 99%

An integrated analysis of public genomic data unveils a possible functional mechanism of psoriasis risk via a long-range ERRFI1 enhancer

Kubota

Suyama

2020

BMC Med Genomics

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Background: Psoriasis is a chronic inflammatory skin disease, for which genome-wide association studies (GWAS) have identified many genetic variants as risk markers. However, the details of underlying molecular mechanisms, especially which variants are functional, are poorly understood. Methods: We utilized a computational approach to survey psoriasis-associated functional variants that might affect protein functions or gene expression levels. We developed a pipeline by integrating publicly available datasets provided by GWAS Catalog, FANTOM5, GTEx, SNP2TFBS, and DeepBlue. To identify functional variants on exons or splice sites, we used a web-based annotation tool in the Ensembl database. To search for noncoding functional variants within promoters or enhancers, we used eQTL data calculated by GTEx. The data of variants lying on transcription factor binding sites provided by SNP2TFBS were used to predict detailed functions of the variants. Results: We discovered 22 functional variant candidates, of which 8 were in noncoding regions. We focused on the enhancer variant rs72635708 (T > C) in the 1p36.23 region; this variant is within the enhancer region of the ERRFI1 gene, which regulates lipid metabolism in the liver and skin morphogenesis via EGF signaling. Further analysis showed that the ERRFI1 promoter spatially contacts with the enhancer, despite the 170 kb distance between them. We found that this variant lies on the AP-1 complex binding motif and may modulate binding levels. Conclusions: The minor allele rs72635708 (rs72635708-C) might affect the ERRFI1 promoter activity, which results in unstable expression of ERRFI1, enhancing the risk of psoriasis via disruption of lipid metabolism and skin cell proliferation. Our study represents a successful example of predicting molecular pathogenesis by integration and reanalysis of public data.

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Section: Discussionmentioning

confidence: 99%

An integrated analysis of public genomic data unveils a possible functional mechanism of psoriasis risk via a long-range ERRFI1 enhancer

Kubota

Suyama

2020

BMC Med Genomics

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“…Hu et al [30] found that Gosha-jinki-gan ( GJG ), composed of 10 herb CHM, is not only useful for DKD but also can improve the glucose utilization and insulin resistance in STZ-induced diabetic rats. Lipid deposition can also lead to insulin resistance and restricted the use of glucose capacity in the muscle [31]. Wen-Pi Tang , which is composed of five CHM ( Rhei Rhizoma , Ginseng Radix , Aconiti Tuber , Zingiberis Rhizoma , and Glycyrrhizae Radix ), showed its protective effects by virtue of the reversal metabolic abnormalities associated with hyperglycemia and hyperlipidemia [32].…”

Section: The Action Mechanisms Of Chm On Dkdmentioning

confidence: 99%

The Efficacy and Mechanism of Chinese Herbal Medicine on Diabetic Kidney Disease

Zhong

Liu

et al. 2019

Journal of Diabetes Research

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Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes and is one of the main causes of end-stage renal disease (ESRD) in many countries. The pathological features of DKD are the hypertrophy of mesangial cells, apoptosis of podocytes, glomerular basement membrane (GBM) thickening, accumulation of extracellular matrix (ECM), glomerular sclerosis, and tubulointerstitial fibrosis. The etiology of DKD is very complicated and many factors are involved, such as genetic factors, hyperglycemia, hypertension, hyperlipidemia, abnormalities of renal hemodynamics, and metabolism of vasoactive substances. Although some achievements have been made in the exploration of the pathogenesis of DKD, the currently available clinical treatment methods are still not completely effective in preventing the progress of DKD to ESRD. CHM composed of natural products has traditionally been used for symptom relief, which may offer new insights into therapeutic development of DKD. We will summarize the progress of Chinese herbal medicine (CHM) in the treatment of DKD from two aspects. In clinical trials, the Chinese herbal formulas were efficacy and safety confirmed by the randomized controlled trials. In terms of experimental research, studies provided evidence for the efficacy of CHM from the perspectives of balancing metabolic disorders, reducing inflammatory response and oxidative stress, antifibrosis, protecting renal innate cells, and regulating microRNA and metabolism. CHM consisting of different ingredients may play a role in synergistic interactions and multiple target points in the treatment of DKD.

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“…It is particularly important for diabetic patients to actively prevent dyslipidemia. Lipid deposition in the liver causes liver insulin resistance (Park et al, 2016 ). Lipotoxicity increased islet cell apoptosis (Huang C. N. et al, 2017 ) and restricted the use of glucose capacity in muscle.…”

Section: Lipid Regulationmentioning

confidence: 99%

Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes

et al. 2018

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Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction. Many effects are attributed to ginsenosides, including gluconeogenesis reduction, improvement of insulin resistance, glucose transport, insulinotropic action, islet cell protection, hepatoprotective activity, anti-inflammatory effect, myocardial protection, lipid regulation, improvement of glucose tolerance, antioxidation, improvement of erectile dysfunction, regulation of gut flora metabolism, neuroprotection, anti-angiopathy, anti-neurotoxic effects, immunosuppression, and renoprotection effect. The molecular targets of these effects mainly contains GLUTs, SGLT1, GLP-1, FoxO1, TNF-α, IL-6, caspase-3, bcl-2, MDA, SOD, STAT5-PPAR gamma pathway, PI3K/Akt pathway, AMPK-JNK pathway, NF-κB pathway, and endoplasmic reticulum stress. Rg1, Rg3, Rb1, and compound K demonstrated the most promising therapeutic prospects as potential adjuvant medicines for the treatment of diabetes. This paper highlights the underlying pharmacological mechanisms of the anti-diabetic effects of ginsenosides.

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Fatty Liver and Insulin Resistance in the Liver-Specific Knockout Mice of Mitogen Inducible Gene-6

Cited by 9 publications

References 28 publications

An integrated analysis of public genomic data unveils a possible functional mechanism of psoriasis risk via a long-range ERRFI1 enhancer

An integrated analysis of public genomic data unveils a possible functional mechanism of psoriasis risk via a long-range ERRFI1 enhancer

The Efficacy and Mechanism of Chinese Herbal Medicine on Diabetic Kidney Disease

Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes

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