Compound 12 is a GPR40 agonist that realizes the full magnitude of efficacy possible via GPR40 receptor agonism. In vitro and in vivo studies demonstrated superior glucose lowering by 12 compared to fasiglifam (TAK-875), in a glucose dependent manner. The enhanced efficacy observed with the full agonist 12 was associated with both direct and indirect stimulation of insulin secretion.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2018.01.013 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Orphan nuclear receptor NR2E3 is a new molecular vulnerability in solid tumors by activating p53.
Cell Death Dis
January 2025
Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield Clinic Health System, Marshfield, WI, USA.
The orphan nuclear receptor NR2E3 has emerged as a potential tumor suppressor, yet its precise mechanisms in tumorigenesis require further investigation. Here, we demonstrate that the full-length protein isoform of NR2E3 instead of its short isoform activates wild-type p53 and is capable of rescuing certain p53 mutations in various cancer cell lines. Importantly, we observe a higher frequency of NR2E3 mutations in three solid tumors compared to the reference population, highlighting its potential significance in tumorigenesis.
View Article and Find Full Text PDFEarly Results of Implementing Rapid Methadone Titration for Hospitalized Patients: A Case Series.
J Gen Intern Med
January 2025
University of California, San Francisco, CA, USA.
Objectives: With the increase in illicit fentanyl use in the USA, hospitals face challenges managing opioid withdrawal and opioid use disorder (OUD). To improve opioid withdrawal and OUD treatment among hospitalized patients with daily fentanyl use, we developed a rapid methadone titration (RMT) protocol. We describe development, implementation, and outcomes during the first 12 weeks.
View Article and Find Full Text PDFN-terminal fragment shedding contributes to signaling of the full-length adhesion receptor ADGRL3.
J Biol Chem
January 2025
Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Department of Molecular Pharmacology and Therapeutics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA. Electronic address:
Most adhesion GPCRs undergo autoproteolytic cleavage during receptor biosynthesis, resulting in non-covalently bound N- and C-terminal fragments (NTF and CTF) that remain associated during receptor trafficking to the plasma membrane. While substantial evidence supports increased G protein signaling when just the CTF is expressed, there is an ongoing debate about whether NTF removal is required to initiate signaling in the context of the wild-type receptor. Here, we use adhesion GPCR latrophilin-3 (ADGRL3) as a model receptor to investigate tethered agonist-mediated activation.
View Article and Find Full Text PDFPro-healing impact of liraglutide on skin wounds in normoglycemic mice.
Int Immunopharmacol
January 2025
Division of Endocrinology, Tongji Hospital, Huazhong University of Science & Technology, Wuhan, 430030, PR China; Branch of National Clinical Research Center for Metabolic Diseases, Hubei, PR China. Electronic address:
Recent studies demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RA) have promising prospects in promoting wound healing. In this study, we intend to investigate the pro-healing effect and potential molecular mechanism of topical administration of GLP-1RA liraglutide on wounds in normoglycemic mice. Two full-thickness wounds were created on the back of the C57BL/6 mice.
View Article and Find Full Text PDFThe Severity of Prostaglandin-Associated Periorbitopathy Did Not Affect the Surgical Effectiveness of the Ahmed Glaucoma Valve.
J Clin Med
December 2024
Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo 693-8501, Japan.
: To report the role of prostaglandin-associated periorbitopathy (PAP) severity on the surgical efficacy of Ahmed Glaucoma Valve (AGV) implantation. : Retrospective observational case series. Participants were the consecutive 102 eyes from 102 Japanese subjects (55 males, 47 females; mean age ± standard deviation, 74.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!