Apolipoprotein status in type 2 diabetes mellitus and its complications

Zhang, Puhong; Gao, Jialin; Pu, Chun; Zhang, Yao

doi:10.3892/mmr.2017.7831

Cited by 39 publications

(29 citation statements)

References 70 publications

(113 reference statements)

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“…The data recognized that IL6 is the top regulator of the DRGs, followed by LEP. The study identified several networks which explore the dysregulation of several functions, including 1456 (23) Note: Data in brackets represent numbers of direct mechanistic network affecting gene expression out of all networks (direct and indirect). cell components, and molecular transport process associated with inflammatory responses that modify the insulin pathway.…”

Section: Discussionmentioning

confidence: 99%

“…The apolipoprotein family is transporters that are involved in lipid metabolism, which altered in diabetes and predisposed to several disorders such as atherosclerosis and cardiovascular diseases. 23 Furthermore, TNF alpha is one of the DRGs which is involved in the transport of lipids, steroids, and efflux of cholesterol. TNF uses different signaling pathways such as NFKBIA, and P38MAPK to exert its effect on lipid transport.…”

Section: Discussionmentioning

confidence: 99%

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<p>Integrated Datasets of Proteomic and Metabolomic Biomarkers to Predict Its Impacts on Comorbidities of Type 2 Diabetes Mellitus</p>

Cheema

Kaur

Fadel

et al. 2020

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The objective of the current study is to accomplish a relative exploration of the biological roles of differentially dysregulated genes (DRGs) in type 2 diabetes mellitus (T2DM). The study aimed to determine the impact of these DRGs on the biological pathways and networks that are related to the associated disorders and complications in T2DM and to predict its role as prospective biomarkers. Methods: Datasets obtained from metabolomic and proteomic profiling were used for investigation of the differential expression of the genes. A subset of DRGs was integrated into IPA software to explore its biological pathways, related diseases, and their regulation in T2DM. Upon entry into the IPA, only 94 of the DRGs were recognizable, mapped, and matched within the database. Results: The study identified networks that explore the dysregulation of several functions; cell components such as degranulation of cells; molecular transport process and metabolism of cellular proteins; and inflammatory responses. Top disorders associated with DRGs in T2DM are related to organ injuries such as renal damage, connective tissue disorders, and acute inflammatory disorders. Upstream regulator analysis predicted the role of several transcription factors of interest, such as STAT3 and HIF alpha, as well as many kinases such as JAK kinases, which affects the gene expression of the dataset in T2DM. Interleukin 6 (IL6) is the top regulator of the DRGs, followed by leptin (LEP). Monitoring the dysregulation of the coupled expression of the following biomarkers (TNF, IL6, LEP, AGT, APOE, F2, SPP1, and INS) highlights that they could be used as potential prognostic biomarkers. Conclusion: The integration of data obtained by advanced metabolomic and proteomic technologies has made it probable to advantage in understanding the role of these biomarkers in the identification of significant biological processes, pathways, and regulators that are associated with T2DM and its comorbidities.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

<p>Integrated Datasets of Proteomic and Metabolomic Biomarkers to Predict Its Impacts on Comorbidities of Type 2 Diabetes Mellitus</p>

Cheema

Kaur

Fadel

et al. 2020

DMSO

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“…Low HDL cholesterol together with higher triglyceride blood concentrations characterize so-called atherogenic dyslipidemia in T2DM patients. Indeed, both hyperglycemia and insulin resistance have been shown to impact HDL particles in different ways: by altering the HDL subspecies proportion in favor of the small-dense HDL 3 with respect to the large HDL 2 ; by altering the HDL proteome; by modifying the enzymatic activity of HDL-associated proteins, such as lecithin-cholesterol acyltransferase (LCAT) and paraoxonase-1 (PON-1); by increasing HDL hepatic catabolism through an enhanced activity of hepatic lipase; and by reducing their anti-inflammatory activity mediated by apolipoprotein A1 (ApoA-I) [13][14][15][16][17]. All these alterations contribute to hindering the anti-inflammatory and antiatherogenic activity of HDL in T2DM patients.…”

Section: Hdl Cholesterol and Metabolic Patternmentioning

confidence: 99%

“…HDL particles are known to be highly heterogeneous in structure and content. The chronic inflammatory state and non-enzymatic apolipoprotein glycation that occur in T2DM contribute to altering the relative composition of HDL and impairing HDL-associated anti-inflammatory and anti-atherogenic properties [2,[14][15][16][17], thus hampering the protective effect of HDL on vessels.…”

mentioning

confidence: 99%

Is HDL cholesterol protective in patients with type 2 diabetes? A retrospective population-based cohort study

et al. 2020

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Background: The protective role of high HDL cholesterol levels against cardiovascular diseases has been recently questioned. Limited data are available on this specific topic in patients with type 2 diabetes mellitus (T2DM). We aimed to evaluate the association of HDL cholesterol concentrations with all-cause and cause-specific mortality in a historical cohort of T2DM patients with 14 years of follow-up. Methods: This is a retrospective population-based cohort study involving 2113 T2DM patients attending the Diabetic Clinic of Asti. Survival analyses were performed to assess hazard ratios for overall and specific-cause mortality by HDL cholesterol tertiles, using the middle HDL cholesterol tertile as a reference. Results: The mean age was 66 ± 11 years; 51.4% of patients had low HDL-cholesterol levels. After a 14-year follow-up, 973/2112 patients had died (46.1%). The HDL cholesterol tertile cutoff points were 37.5 and 47.5 mg/dL (males) and 41.5 and 52.0 mg/dL (females). No associations between lower and upper HDL cholesterol tertiles respectively and all-cause (HR = 1.12; 95% CI 0.96-1.32; HR = 1.11; 0.95-1.30), cardiovascular (HR = 0.97; 0.77-1.23; HR = 0.94; 0.75-1.18) or cancer (HR = 0.92; 0.67-1.25; HR = 0.89; 0.66-1.21) mortality were found. A significantly increased risk for infectious disease death was found both in the lower (HR = 2.62; 1.44-4.74) and the upper HDL-cholesterol tertiles (HR = 2.05; 1.09-3.85) when compared to the reference. Individuals in the upper tertile showed an increased risk for mortality due to diabetes-related causes (HR = 1.87; 1.10-3.15). Conclusions: Our results corroborate the hypothesis that HDL cholesterol levels are nonprotective in T2DM patients. The U-shaped association between HDL-cholesterol levels and mortality associated with infectious diseases should be verified by further studies.

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“…VLDL, which is secreted by the liver, contains apolipoprotein B100 (apoB100) and transports triglycerides. Similar to the IR state, the increased flux of FFA promotes hepatic TG production, which subsequently induces apoB synthesis and secretion [16]. As ApoB is synthesized, it is lipidated by MTTP.…”

Section: Discussionmentioning

confidence: 99%

Sex-dependent effects of ambient PM2.5 pollution on insulin sensitivity and hepatic lipid metabolism in mice

et al. 2020

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Background & aims: Emerging evidence supports ambient fine particulate matter (PM 2.5 ) exposure is associated with insulin resistance (IR) and hepatic lipid accumulation. In this study, we aimed to evaluate the sex-dependent vulnerability in response to PM 2.5 exposure and investigate the underlying mechanism by which PM 2.5 modulates hepatic lipid metabolism.Methods: Both male and female C57BL/6 mice were randomly assigned to ambient PM 2.5 or filtered air for 24 weeks via a whole body exposure system. High-coverage quantitative lipidomics approaches and liquid chromatographymass spectrometry techniques were performed to measure hepatic metabolites and hormones in plasma. Metabolic studies, histological analyses, as well as gene expression levels and molecular signal transduction analysis were applied to examine the effects and mechanisms by which PM 2.5 exposure-induced metabolic disorder.Results: Female mice were more susceptible than their male counterparts to ambient PM 2.5 exposure-induced IR and hepatic lipid accumulation. The hepatic lipid profile was changed in response to ambient PM 2.5 exposure. Levels of hepatic triacylglycerols (TAGs), free fatty acids (FFAs) and cholesterol were only increased in female mice from PM group compared to control group. Plasmalogens were dysregulated in the liver from PM 2.5 -exposed mice as well. In addition, exposure to PM 2.5 led to enhanced hepatic ApoB and microsomal triglyceride transport protein expression in female mice. Finally, PM 2.5 exposure inhibited hypothalamus-pituitary-adrenal (HPA) axis and decreased glucocorticoids levels, which may contribute to the vulnerability in PM 2.5 -induced metabolic dysfunction.Conclusions: Ambient PM 2.5 exposure inhibited HPA axis and demonstrated sex-associated differences in its effects on IR and disorder of hepatic lipid metabolism. These findings provide new mechanistic evidence of hormone regulation in air pollution-mediated metabolic abnormalities of lipids and more personalized care should be considered in terms of sex-specific risk factors.

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Apolipoprotein status in type 2 diabetes mellitus and its complications

Cited by 39 publications

References 70 publications

<p>Integrated Datasets of Proteomic and Metabolomic Biomarkers to Predict Its Impacts on Comorbidities of Type 2 Diabetes Mellitus</p>

<p>Integrated Datasets of Proteomic and Metabolomic Biomarkers to Predict Its Impacts on Comorbidities of Type 2 Diabetes Mellitus</p>

Is HDL cholesterol protective in patients with type 2 diabetes? A retrospective population-based cohort study

Sex-dependent effects of ambient PM2.5 pollution on insulin sensitivity and hepatic lipid metabolism in mice

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