Objective: Targeting the glucagon-like peptide-1 receptor with radiolabeled exendin is a very promising method to noninvasively determine the β cell mass in the pancreas, which is needed to unravel the pathophysiology of type 1 and type 2 diabetes. The present study aimed to explore the effects of both hyperglycemia and insulitis on the uptake of exendin in a spontaneous type 1 diabetes mouse model, nonobese diabetic (NOD) mice.
Methods: NOD mice ( = 75, 7-21 weeks old) were injected intravenously with [In]In-DTPA-exendin-3, and single-photon emission computed tomography (SPECT) images were acquired 1 h pi. The pancreatic accumulation of [In]In-DTPA-exendin-3 was quantified in vivo using SPECT and by ex vivo counting and correlated to the β cell mass (BCM). The influence of insulitis and hyperglycemia on the exendin uptake was assessed.
Results: The pancreas could be visualized longitudinally using SPECT. A linear correlation was found between the BCM (%) and pancreatic uptake (%ID/g) as measured by ex vivo counting (Pearson = 0.64, < 0.001), which was not affected by either insulitis (Pearson = 0.66, = 0.83) or hyperglycemia (Pearson = 0.57, = 0.51). Biodistribution and ex vivo autoradiography revealed remaining [In]In-DTPA-exendin-3 uptake in the pancreas despite total ablation of BCM.
Conclusions: Despite hyperglycemia and severe insulitis, we have found a good correlation between BCM and pancreatic exendin uptake, even in a suboptimal model with relatively high background activity.
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00728 | DOI Listing |
PLoS Genet
January 2025
Department of Biology, Boston University, Boston Massachusetts, United States of America.
The death and clearance of nurse cells is a consequential milestone in Drosophila melanogaster oogenesis. In preparation for oviposition, the germline-derived nurse cells bequeath to the developing oocyte all their cytoplasmic contents and undergo programmed cell death. The death of the nurse cells is controlled non-autonomously and is precipitated by epithelial follicle cells of somatic origin acquiring a squamous morphology and acidifying the nurse cells externally.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) ion channels are members of the cyclic nucleotide-binding family and are crucial for regulating cellular automaticity in many excitable cells. HCN channel activation contributes to pain perception, and propofol, a widely used anesthetic, acts as an analgesic by inhibiting the voltage-dependent activity of HCN channels. However, the molecular determinants of propofol action on HCN channels remain unknown.
View Article and Find Full Text PDFPLoS One
January 2025
School of Information and Technology, Wenzhou Business College, Wenzhou, Zhejiang, China.
Liver cancer is the sixth most frequent malignancy and the fourth major cause of deaths worldwide. The current treatments are only effective in early stages of cancer. To overcome the therapeutic challenges and exploration of immunotherapeutic options, broad spectral therapeutic vaccines could have significant impact.
View Article and Find Full Text PDFCell Rep
January 2025
The Brain Tumor Translational Laboratory, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USA. Electronic address:
The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and the emergence of recurrence. Here, we build a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass and the SVZ of 15 patients and two histologically normal SVZ samples as controls.
View Article and Find Full Text PDFACS Appl Mater Interfaces
December 2024
Institute of Materials for Energy and Environment, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, PR China.
Pd-based nanocatalysts hold significant promise for application in alkaline direct ethanol fuel cells (DEFCs). To address the challenges of low Pd atom utilization and poor reaction kinetics in conventional Pd-based catalysts, a self-etching strategy has been developed to synthesize PdPb nanoparticles (NPs) with tunable size and abundant tensile strain. The nanoparticles demonstrated a markedly enhanced electrocatalytic performance.
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