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Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction.
Protein Sci
January 2025
Department of Chemistry, Columbia University, New York, New York, USA.
The rapid identification of protein-protein interactions has been significantly enabled by mass spectrometry (MS) proteomics-based methods, including affinity purification-MS, crosslinking-MS, and proximity-labeling proteomics. While these methods can reveal networks of interacting proteins, they cannot reveal how specific protein-protein interactions alter protein function or cell signaling. For instance, when two proteins interact, there can be emergent signaling processes driven purely by the individual activities of those proteins being co-localized.
View Article and Find Full Text PDFLinsitinib Decreases Thyrotropin-Induced Thyroid Hormone Synthesis by Inhibiting Crosstalk Between Thyroid-Stimulating Hormone and Insulin-Like Growth Factor 1 Receptors in Human Thyrocytes and in Mice.
Thyroid
December 2024
Laboratory of Endocrinology and Receptor Biology, Bethesda, Maryland, USA.
Thyrotropin receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) have been shown to crosstalk in primary cultures of human thyrocytes (hThyros) and Graves' orbital fibroblasts. The phenomenon of TSHR/IGF-1R crosstalk has been largely studied in the pathogenesis of thyroid eye disease (TED) in human orbital fibroblasts. Here, we investigated the effects of inhibiting the IGF-1R-mediated contribution to crosstalk by linsitinib (Lins), a small-molecule IGF-1R kinase inhibitor, on TSH-induced regulation of thyroperoxidase (TPO) and thyroglobulin (TG) mRNAs and proteins in hThyros and on TPO and TG mRNAs and free thyroxine (fT4) levels in mice.
View Article and Find Full Text PDFGeneration of INS-jGCaMP7f knock-in Ca reporter human embryonic stem cell line, GZLe001-C, using CRISPR/Cas9-based gene targeting.
Stem Cell Res
December 2024
Guangzhou National Laboratory, Guangzhou 510005, China; School of Biomedical Engineering, Guangzhou Medical University, Guangzhou 510180, China; Bioland Laboratory, Guangzhou 510005, China.
As a member of the single-fluorophore genetically encoded calcium indicators (GECIs), jGCaMP7f is widely applied to investigate intracellular Ca concentrations. Here, we established an INS-jGCaMP7f knock-in H1 human embryonic stem cell (hESC) line by integrating jGCaMP7f gene into insulin locus via CRISPR/Cas9 system. The reporter cell line not only effectively labelled the insulin-producing cells induced from hESC, but also reflected the cytosolic change of Ca level in response to different stimuli.
View Article and Find Full Text PDFExpectations and Outcomes From Glucagon-Like Peptide-1 Receptor Agonists As Adjunct Treatment for Type 1 Diabetes - Case Presentations.
J Diabetes Sci Technol
December 2024
Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
Background: Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic beta cells, leading to lifelong insulin dependence. Despite advancements in insulin therapies and glucose monitoring, maintaining optimal blood glucose control remains challenging with common issues like weight gain and glucose variability. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), approved for type 2 diabetes and obesity, are being explored off-label for T1D.
View Article and Find Full Text PDFImproved glycaemic control in people with type 2 diabetes initiating or switching to IDegAsp in a real-world setting in China.
Diabetes Obes Metab
December 2024
Novo Nordisk India Private Limited, Bangalore, India.
Aims: To investigate glycaemic control in Chinese adults with type 2 diabetes (T2D) initiating, or switching to insulin degludec/insulin aspart (IDegAsp), a co-formulation of basal, and bolus insulin, in a real-world setting.
Materials And Methods: A 20-week, prospective, single-arm, open-label, non-interventional study was conducted in Chinese adults with T2D initiating, or switching to IDegAsp after anti-hyperglycaemic treatment with oral antidiabetic drugs (OADs), other insulins, or glucagon-like peptide-1 receptor agonists. The primary endpoint was a change in HbA from baseline to end of the study; the secondary endpoints included a change in fasting plasma glucose and Diabetes Treatment Satisfaction Questionnaire (DTSQ) score.
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