ABCA1 genetic polymorphisms and type 2 diabetes mellitus and its complications

Haerian, Batoul Sadat; Haerian, Monir Sadat; Roohi, Azam; Mehrad‐Majd, Hassan

doi:10.1016/j.mgene.2017.05.007

Cited by 11 publications

(10 citation statements)

References 92 publications

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“…In addition, the RNA-binding protein with multiple splicing (RBPMS), previously uncharacterized in pancreatic β-cells, is known to be up-regulated by pro-inflammatory cytokines like TGF-β and IL-1β [ 88 , 89 ]. Two previous GWAS meta-analyses identified T2D-associated polymorphism (rs9282541 and rs1800977) of a gene encoding a unique ABCA1 [ 90 , 91 ], involved in insulin secretion, glucose tolerance, and cholesterol homeostasis [ 92 , 93 , 94 , 95 ].…”

Section: Resultsmentioning

confidence: 99%

Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery

Kang

Huang

Mandrup‐Poulsen

et al. 2021

IJMS

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Pro-inflammatory cytokines promote cellular iron-import through enhanced divalent metal transporter-1 (DMT1) expression in pancreatic β-cells, consequently cell death. Inhibition of β-cell iron-import by DMT1 silencing protects against apoptosis in animal models of diabetes. However, how alterations of signaling networks contribute to the protective action of DMT1 knock-down is unknown. Here, we performed phosphoproteomics using our sequential enrichment strategy of mRNA, protein, and phosphopeptides, which enabled us to explore the concurrent molecular events in the same set of wildtype and DMT1-silenced β-cells during IL-1β exposure. Our findings reveal new phosphosites in the IL-1β-induced proteins that are clearly reverted by DMT1 silencing towards their steady-state levels. We validated the levels of five novel phosphosites of the potential protective proteins using parallel reaction monitoring. We also confirmed the inactivation of autophagic flux that may be relevant for cell survival induced by DMT1 silencing during IL-1β exposure. Additionally, the potential protective proteins induced by DMT1 silencing were related to insulin secretion that may lead to improving β-cell functions upon exposure to IL-1β. This global profiling has shed light on the signal transduction pathways driving the protection against inflammation-induced cell death in β-cells after DMT1 silencing.

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Section: Resultsmentioning

confidence: 99%

Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery

Kang

Huang

Mandrup‐Poulsen

et al. 2021

IJMS

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“…For example, ABCA1 protein with 10 degrees of interaction plays an inevitable role in regulating lipid metabolism, and defect in this gene disrupts lipid transport of HDL-cholesterol associated with the development of T2DM [ 49 ]. TNF-alpha concentration is also linked with peripheral insulin resistance and elevated plasma glucose as well as insulin levels before the onset of type 2 diabetes [ 50 ]. It was observed that a CXCL8 antagonist ameliorates diabetic nephropathy in diabetic male mice and attenuates high glucose-induced mesangial injury [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

The Antioxidative Role of Natural Compounds from a Green Coconut Mesocarp Undeniably Contributes to Control Diabetic Complications as Evidenced by the Associated Genes and Biochemical Indexes

Das

Al-Araby

et al. 2021

Oxidative Medicine and Cellular Longevity

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The purpose of this study was to look into the effects of green coconut mesocarp juice extract (CMJE) on diabetes-related problems in streptozotocin- (STZ-) induced type 2 diabetes, as well as the antioxidative functions of its natural compounds in regulating the associated genes and biochemical markers. CMJE’s antioxidative properties were evaluated by the standard antioxidant assays of 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide radical, nitric oxide, and ferrous ions along with the total phenolic and flavonoids content. The α-amylase inhibitory effect was measured by an established method. The antidiabetic effect of CMJE was assayed by fructose-fed STZ-induced diabetic models in albino rats. The obtained results were verified by bioinformatics-based network pharmacological tools: STITCH, STRING, GSEA, and Cytoscape plugin cytoHubba bioinformatics tools. The results showed that GC-MS-characterized compounds from CMJE displayed a very promising antioxidative potential. In an animal model study, CMJE significantly ( P < 0.05 ) decreased blood glucose, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, uric acid, and lipid levels and increased glucose tolerance as well as glucose homeostasis (HOMA-IR and HOMA-b scores). The animal’s body weights and relative organ weights were found to be partially restored. Tissue architectures of the pancreas and the kidney were remarkably improved by low doses of CMJE. Compound-protein interactions showed that thymine, catechol, and 5-hydroxymethylfurfural of CMJE interacted with 84 target proteins. Of the top 15 proteins found by Cytoscape 3.6.1, 8, CAT and OGG1 (downregulated) and CASP3, COMT, CYP1B1, DPYD, NQO1, and PTGS1 (upregulated), were dysregulated in diabetes-related kidney disease. The data demonstrate the highly prospective use of CMJE in the regulation of tubulointerstitial tissues of patients with diabetic nephropathy.

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“…Following genome-wide association studies that are considered the most promising in discovering novel disease markers 80 , the genetic architecture of T2D has been well-characterised 81 . A polymorphism in the potassium voltage-gated channel subfamily J member 11 (KCNJ11) gene in a case-control study in KSA 82 , and polymorphisms in the adenosine binding cassette transporter 1 (ABCA1) gene in a meta-analysis 83 , were significantly associated with T2D as they were observed more frequently in T2D patients. Additionally, polymorphisms in the fat mass and obesity-associated (FTO) gene, the so-called ‘obesity gene’, has been recognised to be involved in the progression of insulin resistance and presence of T2D in obese patients 84 , as well as responsiveness to dietary, exercise and drug-based weight loss interventions 85 .…”

Section: Understanding Double Diabetesmentioning

confidence: 99%

Double or hybrid diabetes: A systematic review on disease prevalence, characteristics and risk factors

Khawandanah

2019

Nutr. Diabetes

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Diabetes mellitus is a worldwide epidemic affecting the health of millions of people. While type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing beta cells of the pancreas, type 2 diabetes (T2D) results from a combination of insulin resistance and beta cell insulin secretory defect. Clear definition and diagnosis of these two types of diabetes has been increasing more and more difficult, leading to the inclusion of a new category, namely double or hybrid diabetes (DD) that demonstrates symptoms of both T1D and T2D via the accelerator hypothesis. In this review, we discuss the worldwide prevalence of DD, its main physiological characteristics, including beta-cell autoimmunity, insulin resistance, and cardiovascular disease, the main risk factors of developing DD, mainly genetics, obesity and lifestyle choices, as well as potential treatments, such as insulin titration, metformin and behavioural modifications. Increasing awareness of DD among the general population and primary care practitioners is necessary for successfully treating this complex, hybrid disease in the future.

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ABCA1 genetic polymorphisms and type 2 diabetes mellitus and its complications

Cited by 11 publications

References 92 publications

Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery

Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery

The Antioxidative Role of Natural Compounds from a Green Coconut Mesocarp Undeniably Contributes to Control Diabetic Complications as Evidenced by the Associated Genes and Biochemical Indexes

Double or hybrid diabetes: A systematic review on disease prevalence, characteristics and risk factors

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