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Author: sugaradmin

Autoreactive T Cells and Cytokine Stress Drive β-Cell Senescence Entry and Accumulation in Type 1 Diabetes

August 22, 2025 by sugaradmin

Type 1 diabetes (T1D) results from a complex dialogue between the immune system and islets characterized by T cell–mediated autoimmune destruction of pancreatic β-cells. In this dialogue, β-cell stress responses have emerged as drug targets for slowing T1D progression, including a subpopulation of senescent β-cells that accumulate during T1D in humans and nonobese diabetic (NOD) […]

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Cannabinoid Receptor 2 Agonism Demonstrates Therapeutic Potential in Experimental Models of Relevance to Diabetic Retinopathy

August 22, 2025 by sugaradmin

Evidence of retinal vascular inflammation accompanies diabetic retinopathy (DR) progression, and inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) are experimentally linked to several hallmark DR features, including retinal leukostasis. Cannabinoid receptor 2 (CB2) agonism has been shown to decrease inflammatory cytokine production and leukocyte recruitment and adhesion in nonocular inflammation models, suggesting CB2 […]

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The Cardiac and Hemodynamic Effects of Ketone Bodies Are Abnormal in Patients With Type 1 Diabetes: A Randomized Controlled Trial

August 22, 2025 by sugaradmin

Impaired cardiac ketone oxidative capacity is a possible disease mechanism in the development of diabetic cardiomyopathy. We examined whether the cardiovascular effects of ketone bodies are different in patients with type 1 diabetes (T1D) compared with healthy control individuals. In a single-blind study with a crossover design, nine patients with T1D and eight age-matched, healthy […]

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Dynamic Ca 2+ -Dependent Transcription Links Metabolic Stress to Impaired β-Cell Identity

August 22, 2025 by sugaradmin

By augmenting ATP-sensitive K+ channel–induced membrane depolarization, chronic metabolic stress in prediabetes may increase intracellular Ca2+ concentrations in pancreatic β-cells and cause a loss of cell identity and function. Here, we describe studies of the temporal transcriptomic dynamics induced by sulfonylurea-induced membrane depolarization. Gene expression in isolated islets is highly dynamic, with changes occurring within […]

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Macrophage-Expressed Micropeptide Smim30 Maintains Adipose Tissue Insulin Sensitivity and Safeguards Systemic Metabolic Homeostasis

August 22, 2025 by sugaradmin

A growing number of micropeptides (miPs) have been identified in recent years, but their biological roles remain largely unexplored. We identified a conserved 6-kDa miP, named small integral membrane protein 30 (SMIM30), as a potential metabolic regulator. To study the physiological function of Smim30, we generated a loss-of-function mouse strain using the CRISPR/Cas9-mediated knock-in strategy. […]

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Subclasses of Glucose Trajectories in Early Childhood Stratified the Risk of Abnormal Glucose Tolerance in Adolescence and Young Adulthood

August 21, 2025 by sugaradmin

Early-life exposures may shape long-term effects on glucose regulation. This study aimed to stratify long-term abnormal glucose tolerance (AGT) risk from early childhood. A total of 906 children were enrolled at baseline and reevaluated in adolescence and young adulthood. By using the latent class trajectory analysis, glucose trajectories of children were measured via five–time point […]

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T Cell–Mediated Immunity to Gliadin Is Elicited in the Gut Mucosa of Type 1 Diabetes Patients Only in Presence of Celiac Disease Comorbidity

August 21, 2025 by sugaradmin

Type 1 diabetes (T1D) and celiac disease (CeD) are two strongly associated autoimmune disorders, as they share genetic risk factors and immunopathogenic mechanisms. Several studies suggest an implication of gluten proteins, the causative antigen of CeD, in T1D pathogenesis. We investigated whether a gliadin-specific T-cell reactivity is present in the gut mucosa of children with […]

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Fasting Lowers Glucagon Levels Under Basal Conditions and During Insulin-Induced Hypoglycemia in Individuals With Type 1 Diabetes

August 21, 2025 by sugaradmin

Short-term fasting (<24 h) is common in individuals with type 1 diabetes (T1D), but it is associated with increased risk of hypoglycemia. Current strategies to mitigate this risk include changing the timing and/or dose of insulin; however, it is unclear whether counterregulatory hormone secretion is diminished, which would also contribute to this elevated risk. The […]

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β-Cell Function and Sensitivity to Incretins Before and After Roux-en-Y Gastric Bypass in Individuals With Type 2 Diabetes

August 21, 2025 by sugaradmin

Roux-en-Y gastric bypass (RYGB) improves glucose tolerance in patients with type 2 diabetes, but the effect on β-cell sensitivity to glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) remains unclear. We performed oral glucose tolerance tests (OGTTs) and hyperglycemic clamps (at 15 mmol/L) with GIP, GLP-1, or saline coinfusions before and 1 week and 3 […]

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VAMP8 Is an Endosomal v-SNARE That Supports GLP-1 Receptor Recycling in Pancreatic β-Cells

August 21, 2025 by sugaradmin

Insulin is released by Ca2+-dependent exocytosis of secretory granules, while many receptors, ion channels, and transporters reach the plasma membrane by constitutive exocytosis of endosomal vesicles. Both processes rely on specific sets of soluble N-ethylmaleimide attachment protein receptor (SNARE) proteins for membrane fusion. Here, we used live-cell total internal reflection fluorescence imaging to understand the […]

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