Evaluation of IGFBP-7 DNA methylation changes and serum protein variation in Swedish subjects with and without type 2 diabetes

Gu, Harvest F.; Gu, Tianwei; Hilding, Agneta; Zhu, Yimin; Kärvestedt, Lars; Östenson, Claes‐Göran; Lai, Maode; Kutsukake, Masahiko; Frystyk, Jan; Tamura, Kazuhiro; Brismar, Kerstin

doi:10.1186/1868-7083-5-20

Cited by 46 publications

(40 citation statements)

References 37 publications

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“…Also IGFBP7 has been linked to insulin resistance and Type 2 diabetes, and is further able to interact both with insulin and insulin-like growth factor-1. In a similar approach as above, Gu et al found increased IGFBP7 DNA methylation in men newly diagnosed with Type 2 diabetes, however, no correlation with serum IGFBP7 protein levels was observed [37].…”

Section: Epigenetic Alterations and Insulin Sensitivitymentioning

confidence: 95%

“…However, to be useful as a clinical biomarker, it is also essential to find markers that are reflected in readily accessible tissues or cells, such as blood samples. A few Type 2 diabetes case-control studies have investigated epigenetic alteration in Type 2 diabetes candidate genes in blood samples [35][36][37][38][39]. Toperoff et al detected differentially methylated regions (DMRs) in blood from patients with Type 2 diabetes compared with control individuals, including 6 DMRs in regions previous genetically associated with Type 2 diabetes (CENTD2, FTO, KCNJ11, TCF7L2 and WFS1) [39].…”

Section: Evidence Of Epigenetic Alterations Of Genes Involved In Insumentioning

confidence: 99%

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DNA Methylation as a Diagnostic and Therapeutic Target in the Battle Against Type 2 Diabetes

Rönn

Ling

2015

Epigenomics

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Type 2 diabetes (T2D) develops due to insulin resistance and impaired insulin secretion, predominantly in genetically predisposed subjects exposed to nongenetic risk factors like obesity, physical inactivity and ageing. Emerging data suggest that epigenetics also play a key role in the pathogenesis of T2D. Genome-wide studies have identified altered DNA methylation patterns in pancreatic islets, skeletal muscle and adipose tissue from subjects with T2D compared with nondiabetic controls. Environmental factors known to affect T2D, including obesity, exercise and diet, have also been found to alter the human epigenome. Additionally, ageing and the intrauterine environment are associated with differential DNA methylation. Together, these data highlight a key role for epigenetics and particularly DNA methylation in the growing incidence of T2D.

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Section: Epigenetic Alterations and Insulin Sensitivitymentioning

confidence: 95%

Section: Evidence Of Epigenetic Alterations Of Genes Involved In Insumentioning

confidence: 99%

DNA Methylation as a Diagnostic and Therapeutic Target in the Battle Against Type 2 Diabetes

Rönn

Ling

2015

Epigenomics

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“…In recent years, we have carried out epigenetic studies of the insulin-like growth factors (IGF-I and IGF-II) and their binding proteins (IGFBPs) in diabetes [5][6][7]. IGFBP-2 is the second most abundant circulating IGFBP and expressed by the liver and white adipose tissue [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Analyses of IGFBP2 DNA methylation and mRNA expression in visceral and subcutaneous adipose tissues of obese subjects

Zhang

Frystyk

et al. 2019

Growth Hormone & IGF Research

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Insulin-like growth factor binding-protein 2 (IGFBP-2) is secreted by differentiating white adipocytes. Clinical studies demonstrate that circulating IGFBP-2 levels associated inversely with body mass index (BMI) and insulin resistance. To explore possible epigenetic changes of the IGFBP2 gene in obesity, we analyzed DNA methylation and mRNA expression in adipocytes from different depots. Healthy lean controls (BMI=24.5±0.3 kg/m 2 , n=19) and obese subjects (BMI>35 kg/m 2 , n=24) were recruited. All subjects were Swedish Caucasian. Visceral abdominal adipose tissue (VAT) and subcutaneous adipose tissue (SAT) fragments were homogenized. Genomic DNA and total RNAs were extracted. Four CpG sites in the IGFBP2 gene promoter region were analyzed with bisulfite pyrosequencing. IGFBP2 gene expression at mRNA levels was determined with TaqMan real time RT-PCR. Serum samples were used for measurement of circulating IGFBP-2 and leptin levels. IGFBP2 DNA methylation levels in VAT were increased in obese subjects compared with controls (P<0.05). By contrast, IGFBP2 mRNA expression levels in VAT were lower in obesity subjects than in controls (P<0.05). In SAT, IGFBP2 DNA methylation and RNA expression levels were lower than in VAT, irrespective of obesity. Obese subjects demonstrated increased serum leptin levels (P<0.001) and reduced serum IGFBP-2 levels compared to controls (P<0.05). In conclusion, the current study demonstrates that IGFBP2 DNA methylation levels are increased in VAT from obese subjects. This suggests that IGFBP-2 is epigenetically regulated in abdominal obesity.

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“…As a special member of the IGFBP family, IGFBP7 is commonly considered as a tumour suppressor in various human malignancies, such as lung, colon, liver and pancreatic cancers . Recently, higher serum concentrations of IGFBP7 and IGFBP7 DNA methylation levels have been considered as an increasing risk factor for the development of type 2 diabetes . Lopez‐Bermejo et al suggested that serum IGFBP7 was closely related to body mass index (BMI) in patients with type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Insulin‐like growth factor binding protein 7 accelerates hepatic steatosis and insulin resistance in non‐alcoholic fatty liver disease

Yan

Wang

et al. 2019

Clin Exp Pharma Physio

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| INTRODUC TI ONNon-alcoholic fatty liver disease (NAFLD) is a complex, chronic metabolic disorder characterized by ectopic accumulation of triglycerides (TG) in the liver without a history of alcohol abuse. 1 NAFLD consists of simple steatosis and non-alcoholic steatohepatitis, which ultimately develop into severe cirrhosis and even hepatocellular carcinoma. Recently, the prevalence of NAFLD has increased rapidly and has reached 20%-30% in the urban population of China. 2The pathogenesis of NAFLD is mainly attributed to hepatic lipid accumulation and insulin resistance, since the liver plays a vital role in regulating lipid and glucose metabolism. 3 Insulin resistance resulting from lipid accumulation is referred to as a primary step in the progress of NAFLD due to its crucial role in maintaining the balance of glucose and hepatic TG homeostasis. In the liver, insulin resistance could accelerate NAFLD and lead to hyperinsulinaemia by enhancing the inflow of de novo lipogenesis (DNL). 4 Although various risk factors, such as inflammation, fatty acid synthesis and oxidative stress, have been demonstrated to be involved in NAFLD progression, the exact mechanism underlying NAFLD progression remains unclear. 5Insulin-like growth factor (IGF)-binding protein (IGFBP) 7, also known as mac25, IGFBP-related protein (IGFBP-rP), tumour adhesion factor (TAF) and angiomodulin (AGM), is a secreted, cysteinerich protein that belongs to the IGFBP superfamily. 6 IGFBP7 contains AbstractAn association between increased insulin-like growth factor binding protein-7 (IGFBP7) expression and insulin resistance in metabolic diseases has been reported.However, the role and molecular mechanism of IGFBP-7 in non-alcoholic fatty liver disease (NAFLD) remains largely unknown. Therefore, the potential function of R E FE R E N C E S

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Evaluation of IGFBP-7 DNA methylation changes and serum protein variation in Swedish subjects with and without type 2 diabetes

Cited by 46 publications

References 37 publications

DNA Methylation as a Diagnostic and Therapeutic Target in the Battle Against Type 2 Diabetes

DNA Methylation as a Diagnostic and Therapeutic Target in the Battle Against Type 2 Diabetes

Analyses of IGFBP2 DNA methylation and mRNA expression in visceral and subcutaneous adipose tissues of obese subjects

Insulin‐like growth factor binding protein 7 accelerates hepatic steatosis and insulin resistance in non‐alcoholic fatty liver disease

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