The Diabetes Mellitus–Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(5), P. 1835 - 1835

Published: March 6, 2020

Diabetes mellitus comprises a group of carbohydrate metabolism disorders that share common main feature chronic hyperglycemia results from defects insulin secretion, action, or both. Insulin is an important anabolic hormone, and its deficiency leads to various metabolic abnormalities in proteins, lipids, carbohydrates. Atherosclerosis develops as result multistep process ultimately leading cardiovascular disease associated with high morbidity mortality. Alteration lipid risk factor characteristic atherosclerosis. Possible links between the two depending on altered pathways have been investigated numerous studies. It was shown both types diabetes can actually induce atherosclerosis development further accelerate progression. Elevated glucose level, dyslipidemia, other alterations accompany are tightly involved pathogenesis at almost every step atherogenic process. Chronic inflammation currently considered one key factors present starting earliest stages pathology initiation. may also be regarded possible mellitus. However, data available so far do not allow for developing effective anti-inflammatory therapeutic strategies would stop atherosclerotic lesion progression reduction. In this review, we summarize aspects possibly affect relationship inflammation. We discuss established pathophysiological features link mellitus, such oxidative stress, protein kinase signaling, role certain miRNA epigenetic modifications.

Language: Английский

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Peripheral Neuropathy in Diabetes Mellitus: Pathogenetic Mechanisms and Diagnostic Options

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3554 - 3554

Published: Feb. 10, 2023

Diabetic neuropathy (DN) is one of the main microvascular complications both type 1 and 2 diabetes mellitus. Sometimes, this could already be present at time diagnosis for mellitus (T2DM), while it appears in subjects with (T1DM) almost 10 years after onset disease. The impairment can involve somatic fibers peripheral nervous system, sensory-motor manifestations, as well autonomic neurovegetative multiorgan manifestations through an sympathetic/parasympathetic conduction. It seems that, indirectly directly, hyperglycemic state oxygen delivery reduction vasa nervorum determine inflammatory damage, which turn responsible alteration activity nerves. symptoms signs are therefore various, although symmetrical painful level lower limbs most frequent manifestation. pathophysiological aspects underlying progression DN not entirely clear. purpose review to shed light on recent discoveries diagnostic fields concerning complex complication

Language: Английский

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miRNAs as cornerstones in diabetic microvascular complications

Molecular Genetics and Metabolism, Journal Year: 2022, Volume and Issue: 138(1), P. 106978 - 106978

Published: Dec. 17, 2022

Language: Английский

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Human vitreous in proliferative diabetic retinopathy: Characterization and translational implications

Progress in Retinal and Eye Research, Journal Year: 2019, Volume and Issue: 72, P. 100756 - 100756

Published: April 2, 2019

Language: Английский

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MicroRNAs as Regulators of Insulin Signaling: Research Updates and Potential Therapeutic Perspectives in Type 2 Diabetes

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(12), P. 3705 - 3705

Published: Nov. 22, 2018

The insulin signaling pathway is composed of a large number molecules that positively or negatively modulate specific signal transduction following its binding to the cognate receptor. Given importance final effects transduction, it conceivable many regulators are needed in order tightly control metabolic proliferative functional outputs. MicroRNAs (miRNAs) small non-coding RNA gene expression through their within 3′UTR sequence messenger (mRNA), thus causing mRNA decoy translational inhibition. In last decade, miRNAs have been addressed as pivotal cellular rheostats which fundamental pathways, including transduction. Several studies demonstrated multiple alterations function relevant for development resistance type 2 diabetes (T2D); such highlighted target organs liver, muscles, and adipose tissue. Indirectly, identified modulators inflammation-derived resistance, by controlling/tuning activity innate immune cells tissues. Here, we review main findings on miRNA functions physiologic- T2D resistance- status. Additionally, report latest hypotheses prospective therapies involving potential targets future drugs T2D.

Language: Английский

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circRNAs Signature as Potential Diagnostic and Prognostic Biomarker for Diabetes Mellitus and Related Cardiovascular Complications

Cells, Journal Year: 2020, Volume and Issue: 9(3), P. 659 - 659

Published: March 9, 2020

Circular RNAs (circRNAs) belong to the ever-growing class of naturally occurring noncoding (ncRNAs) molecules. Unlike linear RNA, circRNAs are covalently closed transcripts mostly generated from precursor-mRNA by a non-canonical event called back-splicing. They highly stable, evolutionarily conserved, and widely distributed in eukaryotes. Some believed fulfill variety functions inside cell mainly acting as microRNAs (miRNAs) or RNA-binding proteins (RBPs) sponges. Furthermore, mounting evidence suggests that misregulation is among first alterations various metabolic disorders including obesity, hypertension, cardiovascular diseases. More recent research has revealed also play substantial role pathogenesis diabetes mellitus (DM) related vascular complications. These findings have added new layer complexity our understanding DM underscored need reexamine molecular pathways lead this disorder context epigenetics circRNA regulatory mechanisms. Here, I review current knowledge about dysregulation describe their potential innovative biomarkers predict diabetes-related (CV) events. Finally, discuss some actual limitations promise these RNA emerging therapeutics provide recommendations for future on circRNA-based medicine.

Language: Английский

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MicroRNAs’ role in the environment-related non-communicable diseases and link to multidrug resistance, regulation, or alteration

Environmental Science and Pollution Research, Journal Year: 2021, Volume and Issue: 28(28), P. 36984 - 37000

Published: May 27, 2021

Language: Английский

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The circulating exosomal microRNAs related to albuminuria in patients with diabetic nephropathy

Journal of Translational Medicine, Journal Year: 2019, Volume and Issue: 17(1)

Published: July 22, 2019

Diabetic nephropathy (DN) is associated with high risk of cardiovascular disease and mortality. Exosomal microRNAs (miRNAs) regulate gene expression in a variety tissues play important roles the pathology various diseases. We hypothesized that exosomal miRNA profile would differ between DN patients without nephropathy. prospectively enrolled 74 participants, including healthy volunteers (HVs), diabetic nephropathy, those DN. The serum profiles participants were examined using RNA sequencing. levels 107 miRNAs differed HVs DN, whereas 95 Among these miRNAs, we found 7 (miR-1246, miR-642a-3p, let-7c-5p, miR-1255b-5p, let-7i-3p, miR-5010-5p, miR-150-3p) uniquely up-regulated compared to HVs, miR-4449 was highly expressed A pathway analysis revealed eight are likely involved MAPK signaling, integrin function angiogenesis, regulation AP-1 transcription factor. Moreover, they all significantly correlated degree albuminuria. Patients have different HVs. These may be promising candidates for diagnosis treatment disease.

Language: Английский

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The Effects of Dapagliflozin on Systemic and Renal Vascular Function Display an Epigenetic Signature

The Journal of Clinical Endocrinology & Metabolism, Journal Year: 2019, Volume and Issue: 104(10), P. 4253 - 4263

Published: June 4, 2019

Abstract Context Mechanisms mediating the cardiovascular and renal protection exerted by SGLT2 inhibitors are still partially unknown. We investigated whether dapagliflozin modulates systemic vascular function structure, induces epigenetic modifications. Subjects Methods Forty hypertensive patients with type 2 diabetes were randomly assigned to 4-week treatment 10 mg or hydrochlorothiazide (HCT) 12.5 mg. Routine analyses; plasma renin activity; aldosterone, catecholamine, 24-hour urinary electrolyte levels; flow-mediated dilation (FMD) of brachial artery; carotid-femoral pulse-wave velocity (PWV); augmentation index; resistive index dynamic (DRIN) measured at baseline after treatment. Circulating miRNAs (miRs) related heart failure (miR30e-5p, miR199a-3p), endothelial dysfunction (miR27b miR200b), (miR130b-3p, miR21-5p) assessed effects treatments. Results Dapagliflozin HCT marginally lowered blood pressure. Fasting glucose was lowered, whereas diuresis, glycosuria, osmolar clearance increased (P < 0.001 for all), without affecting sodium excretion glomerular filtration rate. Magnesium levels significantly = 0.02). Neither nor modified FMD PWV. DRIN did not vary in group, it group 0.047 time interaction). Both treatments induced variations expression some miRs; dapagliflozin, but HCT, up-regulated miR30e-5p downregulated miR199a-3p. Conclusion A putative regulation protecting effect found. might exert nephroprotection preserving vasodilating capacity.

Language: Английский

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Downregulation of microRNA-146a in diabetes, obesity and hypertension may contribute to severe COVID-19

Medical Hypotheses, Journal Year: 2020, Volume and Issue: 146, P. 110448 - 110448

Published: Dec. 9, 2020

Language: Английский

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