Month: June 2025

Recent evidence has shown that adipose tissue eventually develops fibrosis through complex cellular cross talk. Although advances in single-cell transcriptomics have provided new insights into cell diversity during this process, little is known about the interactions among the distinct cell types. In this study, we used single-cell analytical approaches to investigate cell-to-cell communications between macrophages […]

G protein–coupled receptor 119 (GPR119) is predominantly expressed in pancreatic β-cells, enteroendocrine cells, and the liver. It is a novel therapeutic for dyslipidemia and type 2 diabetes. DA-1241, a GPR119 agonist, improves glucose tolerance by inhibiting gluconeogenesis and enhancing insulin secretion. It mitigates hepatic inflammation by inhibiting NFκB signaling. However, the mechanism by which DA-1241 […]

Activation of GPR119 receptors, expressed on enteroendocrine and pancreatic islet cells, augments glucagon counterregulatory responses to hypoglycemia in preclinical models. We hypothesized that MBX-2982, a GPR119 agonist, would augment counterregulatory responses to experimental hypoglycemia in participants with type 1 diabetes (T1D). To assess this, we designed a phase 2a, double-masked, crossover trial in 18 participants […]

Since little is known about the disposition index (DI) in autoantibody-positive individuals, we have assessed whether DI has a similar association between insulin secretion and sensitivity to the association observed in other populations. In TrialNet Pathway to Prevention (TNPTP; n = 6,620) and Diabetes Prevention Trial–Type 1 (DPT-1; n = 704) study participants, two secretion-sensitivity […]

Intrahepatic islet transplantation is followed by islet loss due to the instant blood-mediated inflammatory response (IBMIR) in which platelet activation plays a key role. The KEATSTF-fragment (KF7), a newly discovered platelet inhibitor that interferes with the formation of the 14-3-3ζ–c-Src–integrin-β3 complex, holds significant potential in inhibiting IBMIR without causing significant bleeding. This study introduces a […]

Glycated hemoglobin has shown disagreements with other glycemic indices; termed the glycation gap. The glycation gap can be influenced by nonglycemic factors, such as protein deglycation, through the fructosamine-3-kinase (FN3K) enzyme. This cross-sectional study aimed to examine whether single nucleotide polymorphisms (SNPs) in the FN3K gene can explain the glycation gap. Among the 826 participants, […]

Pathologic signaling via the receptor for advanced glycation end products (RAGE) is critical to diabetic kidney disease (DKD) development, whereas RAGE deletion is renoprotective. Noncoding RNAs (ncRNAs), including miRNAs, also play key roles in DKD, including in renal fibrosis. However, the involvement of ncRNAs in RAGE signaling remains unclear. This study investigated the regulation of […]

Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. It is generally defined as glucose intolerance with onset or first recognition during pregnancy. The pathogenesis of GDM has long been attributed to inadequate pancreatic β-cell compensation for the physiological insulin resistance of pregnancy. This defect is thought to resolve after […]

Wolfram syndrome 1 (WS1) is a rare genetic disorder caused by WFS1 variants that disrupt wolframin, an endoplasmic reticulum-associated protein essential for cellular stress responses, Ca2+ homeostasis, and autophagy. Here, we investigated how the c.316-1G>A and c.757A>T WFS1 mutations, which yield partially functional wolframin, affect the molecular functions of β-cells and explored the therapeutic potential […]

Obesity is a growing global health threat, and inducing browning of white adipose tissue (WAT) to increase energy expenditure has become an attractive strategy for treating obesity and related metabolic complications. BRCA1-associated protein 1 (BAP1), a ubiquitin C-terminal hydrolase domain–containing deubiquitinase expressed broadly across tissues, has previously been shown to play an important role in […]