Until recently, the prevalence of endogenous Cushing syndrome has been considered to be low. However, improved diagnostic strategies and increased awareness have broadened our understanding of hypercortisolism and its role in the pathophysiology of type 2 diabetes, obesity, hypertension, and cardiovascular disease. Recent studies from Europe, South America, and the U.S. have demonstrated that a […]
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Proteogenomic Discovery of Novel Open Reading Frames With HLA Immune Presentation on Human β-Cells
Ribosome profiling (Ribo-seq) measures translational regulation and reveals novel or unannotated open reading frames (nuORFs) otherwise difficult to identify. Recent reports demonstrate that nuORFs regulate gene expression and immune recognition, highlighting their emerging biological roles. Pancreatic β-cells are critical for maintaining euglycemic conditions, and β-cell impairment contributes to diabetes development. Identification of nuORF and protein/peptide […]
Read MoreMultiomics Integration of Epigenetics, Proteomics, and Metabolomics Identifies Putative Drug Targets and Improves Early Prediction for Diabetes
Diabetes holds significant social importance due to its high incidence rate and multitude of associated complications. The identification of diabetes biomarkers and the understanding of the intricate biological mechanisms underlying diabetes are crucial for the early diagnosis and treatment of diabetes. In this study, we conducted comprehensive omics profiling of CpGs, plasma proteins, and serum […]
Read MoreGenome-Wide Association Study of Hypoglycemia in Adults With Diabetes in the Million Veteran Program
Hypoglycemia is a preventable adverse treatment effect in diabetes patients, but genetic markers to identify those with increased susceptibility are lacking. We performed a case/control genome-wide association study (GWAS) of hypoglycemia in U.S. Million Veteran Program (MVP) participants with medication-treated diabetes. Case participants had an outpatient random serum/plasma glucose <70 mg/dL or an emergency department […]
Read MoreCombined Weight Loss and Exercise Training Alters Skeletal Muscle Subcellular Lipid Localization and Intermuscular Adipose Tissue Cellular Composition
Subcellular lipid accumulation and intermuscular adipose tissue (IMAT) accumulation are associated with insulin resistance, but the impact of combined weight loss and exercise training on localization of lipids and IMAT cellular composition is not known. Twenty-one adults with obesity (18 female and 3 male; 46 ± 2 years; 35.0 ± 0.9 kg/m2) completed a 3-month […]
Read MoreGenotype-Phenotype Discrepancies in Family Members With a Novel Glucokinase Mutation: Insights Into GCK-MODY and Its Interplay With Insulin Resistance
Heterozygous inactivating mutations in the glucokinase (GCK) gene cause maturity-onset diabetes of the young (GCK-MODY). We identified a novel variant of uncertain significance in the GCK gene (c.77A>T, p.Q26L) in two family members exhibiting contrasting diabetic phenotypes. To explore the diabetogenic potential of the GCK-Q26L mutation and investigate the mono- and polygenetic factors contributing to […]
Read MoreNovel Function of Osteoprotegerin in the Modulation of Glucose Metabolism in the Liver via mTORC1
Osteoprotegerin (OPG) has emerged as a pivotal factor in metabolic disease pathology; however, its role in hepatic glucose metabolism remains poorly understood. We demonstrated a pronounced reduction in hepatic OPG expression in obese mice, attributable to DNA hypermethylation mediated by DNMT3α. Opg overexpression in the liver reduced the basal metabolic rate and exacerbated glucose metabolism […]
Read MoreRegulatory Roles of IGF2R in Insulin Secretion and Adaptive β-Cell Proliferation
Insulin-like growth factor-2 receptor (IGF2R), also known as cation-independent mannose-6-phosphate receptor, is localized in cytosolic vesicles and is unique in its ability to transport enzymes to the lysosome and to clear IGF2 from the cell surface by acting as a scavenger receptor. To evaluate the direct role of IGF2R in β-cell biology, we undertook complementary […]
Read MoreTrem2 + Macrophages Alleviate Renal Tubule Lipid Accumulation and Ferroptosis in Diabetic Nephropathy by Repressing IL-1β–Mediated CD36 Expression
The presence of macrophages surrounding lipotoxic tubular epithelial cells (TECs) is a hallmark of diabetic nephropathy (DN). Nevertheless, the mechanisms of communication between these cell types are not well understood. Previous studies have revealed a unique subset of macrophages that express triggering receptor expressed on myeloid cells 2 (Trem2) in kidneys of human patients and […]
Read Moreβ-Cell Mass in Individuals With and Without Postbariatric Hypoglycemia After Roux-en-Y Gastric Bypass
Postbariatric hypoglycemia (PBH) is a serious complication of Roux-en-Y gastric bypass (RYGB), characterized by severe hypoglycemia that may lead to loss of consciousness and seizures. The exact mechanism of PBH is poorly understood. One potential mechanism is β-cell expansion. To this end, we investigated β-cell mass in individuals with and without PBH after RYGB using […]
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