Diabetic retinopathy (DR) is a leading cause of vision loss in working-age adults and often progresses to proliferative diabetic retinopathy (PDR) with irreversible complications. Anti–vascular endothelial growth factor (VEGF) therapy remains the first-line treatment; however, resistance poses a significant challenge, necessitating alternative therapeutic targets. This study explores the role of angiopoietin-like protein 4 (ANGPTL4) in […]
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Normalization of Insulin Resistance Rather Than Hyperglycemia Before Stroke Improves Functional Outcomes in a Mouse Model of Type 2 Diabetes
Prestroke hyperglycemia and insulin resistance (IR) independently correlate with poor stroke outcomes in type 2 diabetes (T2D), although their causative effect is undetermined. Interestingly, an increasing body of evidence points toward the importance of IR in determining stroke outcomes. Filling this gap is fundamental to identifying effective anti-T2D strategies to improve stroke prognosis in people […]
Read MoreMesenchymal Stem Cell and Secretome Treatments Inhibit the mTOR–NOX4 Pathway in Diabetic Kidney Disease
Diabetic kidney disease (DKD) is a major complication of diabetes characterized by progressive renal dysfunction driven by oxidative stress and inflammation involving mammalian target of rapamycin (mTOR) and NADPH oxidase (NOX) pathways. Mesenchymal stem cells (MSCs) have gained attention for their regenerative and immunomodulatory properties in attenuating DKD, but the mechanisms behind their protective effects […]
Read MoreQuantitative β-Cell Mass Imaging Redefines Disease Staging and Glycemic Control in Type 1 Diabetes
Noninvasive measurement of pancreatic β-cell mass remains an important unmet need in type 1 diabetes because conventional surrogate markers, such as C-peptide, often lack sensitivity in advanced disease. This study evaluated the glucagon-like peptide 1 receptor–targeted positron emission tomography tracer, 18F-labeled exendin-4–based probe conjugated with polyethylene glycol, [18F]FB(ePEG12)12-exendin-4 (18F-exendin-4), to determine its ability to visualize […]
Read MoreMetabolite Erythritol in 24-Hour Urine Is Associated With Higher Intrahepatic Lipid Content: The Maastricht Study
The pentose phosphate pathway (PPP) furnishes NADPH for hepatic de novo lipogenesis, driving intrahepatic lipid (IHL) accumulation. The aim of the current study was to examine the association between the PPP, proxied by 24-h urinary erythritol, and IHL content at the population level. We used cross-sectional data from the Maastricht Study, a population-based cohort study […]
Read MoreMultiple Mechanisms Contribute to Robust Type 1 Diabetes Protection in Nfkbid – Overexpressing NOD Mice
We previously reported that transgenic overexpression of Nfkbid in NOD mice led to robust type 1 diabetes protection associated with enhanced negative selection of autoreactive T cells and expansion of regulatory T cells (Tregs) with increased suppressive capacity. The goal of this study was to further identify cellular and molecular mechanisms underlying strong protection from […]
Read MoreIDH3A Deficiency Compromises Adaptive Thermogenesis and Exacerbates Obesity-Induced Metabolic Dysfunction via Impaired BCKDHA-Dependent BCAA Catabolism
Adaptive thermogenesis in beige adipocytes is essential for maintaining energy homeostasis and preventing obesity. Emerging evidence suggests that human visceral adipose tissue harbors adipocytes with beige-like thermogenic features, enabling analysis of thermogenic gene regulation in humans. Isocitrate dehydrogenase 3A (IDH3A) is a rate-limiting enzyme of the tricarboxylic acid cycle, yet its function in adipocytes remains […]
Read MoreTomosyn-2 Regulates Postnatal β-Cell Expansion and Insulin Secretion to Maintain Glucose Homeostasis
The transition from a proliferative to a functionally mature state is a critical phase in postnatal pancreatic β-cell development, yet the molecular mechanisms coordinating this shift remain poorly understood. Here, we identify tomosyn-2 as a key regulator that restrains β-cell maturation and insulin secretory capacity. Tomosyn-2 expression progressively declines in mouse islets with age, coinciding […]
Read MoreAssociations of Combined Genetic and Lifestyle Risks With Incident Type 2 Diabetes in the UK Biobank
Type 2 diabetes (T2D) results from the interplay of genetic susceptibility and an unhealthy lifestyle, but their combined effects are not well studied. We examined whether unhealthy modifiable behaviors were associated with similar increases in the risk of incident T2D in individuals with different levels of genetic risk. Among 332,251 UK Biobank participants without diabetes, […]
Read MoreDiabetes Spotlight: Jennifer Estall, PhD—Identifying Signals Between the Pancreas and Liver
In the age of peptides, Jennifer Estall often hears an iteration of the same joke: diabetes is cured now; your career is over. “Which isn’t true, of course,” she says. Still, like most good jokes, this one also points to a truth, namely, that Estall, earning her doctorate in the early 2000s just as glucagon-like […]
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