Author: sugaradmin

Endothelial dysfunction contributes to the pathogenesis and progression of diabetes and atherosclerotic cardiovascular diseases (ASCVDs) with sirtuin-6 (SIRT6) downregulation in vascular endothelial cells (ECs). Here, the effects and underlying mechanisms of SIRT6 as a deacetylase were investigated in maintaining EC integrity against diabetes-exacerbated atherogenesis. SIRT6 downregulation was exacerbated in carotid artery ECs of Apoe−/− mice […]

Type 1 diabetes is driven by both β-cell dysfunction and an autoreactive immune system, resulting in β-cell destruction and hyperglycemia. We previously showed that pharmacological modulation of prostaglandin E2 (PGE2) receptor (EP) signaling protects β-cells from cytokine-mediated death ex vivo and relieves oxidative stress and maintains β-cell identity in a mouse model of type 2 […]

The intraislet heparan sulfate (HS) barrier is essential for β-cell survival, yet its role in type 1 diabetes (T1D) remains incompletely understood. We investigated the expression pattern, pathogenic function, and therapeutic potential of the heparanase (HPSE)-HS axis in T1D by integrating single-cell RNA sequencing data sets from human and mouse islets and peripheral immune cells, […]

Hyperglycemia is a hallmark of type 2 diabetes and a key pathogenic driver of diabetes complications. Cullin RING E3 ligases (CRLs) are multisubunit E3 ubiquitin ligases that mediate cellular protein turnover. The activity of CRLs requires cullin neddylation, a posttranslational modification that can be pharmacologically targeted with therapeutic potentials. By using hyperinsulinemic-euglycemic clamp analysis, we […]

Proinflammatory T helper 1 (Th1) CD4 T cells orchestrate β-cell destruction in type 1 diabetes (T1D) by using glycolysis for effector responses. By targeting T-cell metabolism, we may identify novel mechanisms and therapies to effectively delay T cell–mediated autoimmune diseases like T1D. We hypothesized that treatment of prediabetic mice with the glycolysis inhibitor, 2-deoxyglucose (2-DG), […]

Excess adiposity is associated with insulin resistance and pancreatic β-cell dysfunction. We show that palmitoylation cycling in white adipose tissue (WAT) balances insulin sensitivity and insulin secretion. WAT and brown adipose tissue (BAT) ablation of acyl-protein thioesterase 1 (APT1) in APT1-deficient (knockout) mice (APT1-AdipoKO) resulted in increased body weight and exacerbated insulin resistance when the […]

Immunosenescence, characterized by functional decline and altered phenotypes of immune cells with age, can disturb immune tolerance and promote autoreactive responses. Type 1 diabetes (T1D) has traditionally been viewed as a disease of immune dysregulation that leads to the autoimmune destruction of pancreatic β-cells. Emerging evidence suggests that senescence contributes to both the onset and […]

Type 2 diabetes mellitus (T2DM) disrupts the quantity, phenotype, and function of circulating vascular regenerative (VR) progenitor cells that are critical to vessel repair. These impairments include reduced progenitor clonogenicity, mobilization and homing to areas of ischemia, and imbalances in secretory function, collectively contributing to poor vascular healing and complications such as peripheral artery disease, […]

Prediabetes is highly prevalent and biologically heterogeneous, yet current glycemic definitions do not adequately capture differences in cardiometabolic and kidney risk. We aimed to identify metabolically defined subtypes of prediabetes using circulating metabolites and to examine their associations with cardiovascular-kidney-metabolic outcomes. We analyzed 24,638 participants with prediabetes from the UK Biobank who had metabolomics data […]