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
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. […]
Read MoreSubclasses of Glucose Trajectories in Early Childhood Stratified the Risk of Abnormal Glucose Tolerance in Adolescence and Young Adulthood
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 […]
Read MoreT Cell–Mediated Immunity to Gliadin Is Elicited in the Gut Mucosa of Type 1 Diabetes Patients Only in Presence of Celiac Disease Comorbidity
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 […]
Read MoreFasting Lowers Glucagon Levels Under Basal Conditions and During Insulin-Induced Hypoglycemia in Individuals With Type 1 Diabetes
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 […]
Read Moreβ-Cell Function and Sensitivity to Incretins Before and After Roux-en-Y Gastric Bypass in Individuals With Type 2 Diabetes
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 […]
Read MoreVAMP8 Is an Endosomal v-SNARE That Supports GLP-1 Receptor Recycling in Pancreatic β-Cells
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 […]
Read MoreRevealing Cerebral Microvascular Changes in Diabetic Rodents With Ultrasound Localization Microscopy
Microvasculature and hemodynamic changes in the cerebrovascular system are valuable indicators for the investigation of diabetic cerebrovascular disease. However, it is challenging for conventional imaging techniques to capture these minute features, meaning that the specific effects of diabetes on the brain vasculature and its potential disruption of brain function remain inadequately investigated. Ultrasound localization microscopy, […]
Read MoreType 1 Diabetes Autoantibodies in Acute, Recurrent Acute, and Chronic Pancreatitis
Pancreatogenic or type 3c diabetes, which occurs as a consequence of pancreatitis, may have several mechanisms. Mechanisms overlapping with those of type 2 diabetes have been explored, including insulin resistance and insulin deficiency. However, autoimmune mechanisms in response to unmasking β-cell antigens, similar to those of type 1 diabetes (T1D), have not been thoroughly examined. […]
Read MoreReducing PTP1B in the Hippocampus Protects Against Cognitive Decline in Prediabetes
The prevalence of prediabetes is increasing globally, driven by rising obesity rates. Prediabetes increases the risk of neurodegenerative diseases, which are linked by neuroinflammation. Protein tyrosine phosphatase 1B (PTP1B), a neuroinflammatory and negative synaptic regulator, is involved in the pathogenesis of neurodegenerative processes. However, the role and underlying mechanisms of PTP1B in prediabetes-induced cognitive impairment […]
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