AI Article Synopsis
Article Abstract
Background: The mechanism of pyruvate kinase M2 (PKM2)-mediated inflammatory signalling in macrophages when plaques rupture and the impact of hyperglycaemia on the signalling are unclear. The present study aimed to explore the impact of hyperglycaemia on PKM2-mediated NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome/stress granule signalling in macrophages and its correlation with plaque vulnerability in vivo and in vitro.
Methods: From July to December 2019, 80 patients with coronary heart disease (CHD) were divided into acute ST-segment elevation myocardial infarction (STEMI) (n = 57) (DM-STEMI, n = 21; non-DM-STEMI, n = 36) and stable CHD (SCHD) groups (n = 23). Circulating mononuclear cells were isolated. The value of peak troponin I (TnI), the Global Registry of Acute Coronary Events (GRACE) risk score, and the expression levels of the related markers were quantified and compared. In vitro studies on the THP-1 cells were also performed.
Results: The DM-STEMI group had a higher value of peak TnI and a higher GRACE risk score than the non-DM-STEMI group (p < 0.05). The highest expression levels of PKM2, NLRP3, interleukin (IL)-1β, and IL-18 and the lowest expression level of GTPase activating protein (SH3 domain)-binding protein 1 (G3BP1) (a stress granule marker protein) were observed in the DM-STEMI group, and they were followed by the non-DM-STEMI group and the SCHD group (p < 0.05). In vitro studies showed similar results and that TEPP-46 (a PKM2 activator) and 2-deoxy-d-glucose (a toxic glucose analogue) reversed the hyperglycaemia-induced increase in the NLRP3 inflammasome and decrease in G3BP1 expression.
Conclusion: Hyperglycaemia might increase the activation of PKM2-mediated NLRP3 inflammasome/stress granule signalling and increase plaque vulnerability, associating it with worse prognosis. PKM2 may be a novel prognostic indicator and a new target for the treatment of patients with CHD and DM.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.metabol.2020.154231 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The effect of renal function on the clinical outcomes and management of patients hospitalized with hyperglycemic crises.
Front Endocrinol (Lausanne)
January 2025
Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Background: The global prevalence of diabetes has been rising rapidly in recent years, leading to an increase in patients experiencing hyperglycemic crises like diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). Patients with impaired renal function experience a delay in insulin clearance, complicating the adjustment of insulin dosing and elevating hypoglycemia risk. Accordingly, this study aims to evaluate the impact of renal function on the safety and efficacy of insulin use in patients with isolated DKA or combined DKA/HHS.
View Article and Find Full Text PDFMulti-ancestry genome-wide association analyses: a comparison of meta- and mega-analyses in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.
BMC Genomics
January 2025
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Background: There is increasing need for effective incorporation of high-dimensional genetics data from individuals with varied ancestry in genome-wide association (GWAS) analyses. Classically, multi-ancestry GWAS analyses are performed using statistical meta-analysis to combine results conducted within homogeneous ancestry groups. The emergence of cosmopolitan reference panels makes collective preprocessing of GWAS data possible, but impact on downstream GWAS results in a mega-analysis framework merits investigation.
View Article and Find Full Text PDFBenefits of Cilostazol's Effect on Vascular and Neuropathic Complications Caused by Diabetes.
Med Sci (Basel)
December 2024
Department of Molecular Pathobiology, New York University, New York, NY 10010, USA.
Diabetes mellitus (DM) is a global health concern with a rising incidence, particularly in aging populations and those with a genetic predisposition. Over time, DM contributes to various complications, including nephropathy, retinopathy, peripheral arterial disease (PAD), and neuropathy. Among these, diabetic neuropathy and PAD stand out due to their high prevalence and significant impact on patients' quality of life.
View Article and Find Full Text PDFBackground: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, mostly resulting from impaired insulin production and diminished glucose metabolism regulation. Qiwei Baizhu San (QWBZS) is a classic formula used in traditional Chinese medicine for the treatment of T2DM. A comprehensive analysis of the efficacy and safety of QWBZS in the treatment of T2DM is essential.
View Article and Find Full Text PDFInteraction of B0AT1 deficiency and diet on metabolic function and diabetes incidence in male NOD mice.
Endocrinology
January 2025
Australian National University School of Medicine and Psychology, Australian National University, Acton, ACT, 0200, Australia.
Context: The obesity epidemic parallels an increasing type 1 diabetes incidence, such that westernized diets, containing high fat, sugar and/or protein, through inducing nutrient-induced islet beta-cell stress, have been proposed as contributing factors. The broad-spectrum neutral amino acid transporter (B0AT1), encoded by Slc6a19, is the major neutral amino acids transporter in intestine and kidney. B0AT1 deficiency in C567Bl/6J mice, causes aminoaciduria, lowers insulinemia and improves glucose tolerance.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!