Glucagon receptor plays an important role in the regulation of glucose metabolism. Studies have revealed that glucagon receptor antagonism is a potential effective treatment for diabetes. However, the functions of GCGR have not been fully illustrated. Although two Gcgr truncation knockout mice models have been widely used for GCGR function studies, truncated gene may remain neomorphic and/or dominant-negative function. In this study, we took the advantages of Crispr-Cas9 technique and generated a novel allele of GCGR in the mouse that yields complete loss of GCGR protein. Our studies reveal that complete deletion of Gcgr results in hyperglucagonemia, α-cell hyperplasia, improvement of glucose tolerance. These results are similar to the Gcgr-truncated mutation in mice. Hence, we provide a novel strain of GCGR knockout mice for the GCGR function studies.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2022.12.079 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pharmacologic Management of Heart Failure with Preserved Ejection Fraction (HFpEF) in Older Adults.
Drugs Aging
January 2025
Program for the Care and Study of the Aging Heart, Department of Medicine, Weill Cornell Medicine, 420 East 70th St, New York, NY, LH-36510063, USA.
There are several pharmacologic agents that have been touted as guideline-directed medical therapy for heart failure with preserved ejection fraction (HFpEF). However, it is important to recognize that older adults with HFpEF also contend with an increased risk for adverse effects from medications due to age-related changes in pharmacokinetics and pharmacodynamics of medications, as well as the concurrence of geriatric conditions such as polypharmacy and frailty. With this review, we discuss the underlying evidence for the benefits of various treatments in HFpEF and incorporate key considerations for older adults, a subpopulation that may be at higher risk for adverse drug events.
View Article and Find Full Text PDFPerioperative Use of GLP-1 Receptor Agonists in Patients Undergoing Cardiac Procedures: A Scoping Review.
Heart Lung Circ
January 2025
Department of Cardiology, St Vincent's Hospital Melbourne, Melbourne, Vic, Australia; Heart, Exercise and Research Trials (HEART) Laboratory, St Vincent's Institute of Medical Research, Melbourne, Vic, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Vic, Australia.
Background: Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapies are increasingly used for the treatment of type 2 diabetes mellitus and obesity. Despite growing awareness of potentially increased risk of pulmonary aspiration due to delayed gastric emptying, the risks and benefits of their perioperative use in patients undergoing cardiac procedures remains unexplored. A scoping review was performed to investigate the perioperative GLP-1RA use in patients undergoing cardiac procedures and recommendations.
View Article and Find Full Text PDFDiscovery of Selenium-Containing Derivatives as Potent and Orally Bioavailable GLP-1R Agonists.
J Med Chem
January 2025
Jiang Su Key Laboratory of Drug Design and Optimization and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Glucagon-like peptide-1 receptor (GLP-1R) is a well-established target for the treatment of type 2 diabetes mellitus (T2DM) and obesity. The development of orally bioavailable and long-acting small-molecule GLP-1R agonists is a pursuit in both academia and industry. Herein, new selenium (Se)-containing compounds were designed using a Se-oxygen bioisostere strategy on the danuglipron scaffold.
View Article and Find Full Text PDFEndoscopy and Anesthesia Outcomes Associated with Glucagon-Like Peptide-1 Receptor Agonist use in Patients Undergoing Outpatient Upper Endoscopy.
Gastrointest Endosc
January 2025
Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Division of Digestive Diseases, Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH. Electronic address:
Background And Aims: Glucagon-like peptide-1 receptor agonists (GLP1RAs) can cause delayed gastric emptying, raising concern for retained gastric contents (RGCs) during endoscopy and adverse anesthesia events. We aimed to determine associations between GLP1RA and endoscopy and anesthesia outcomes.
Methods: This single-center retrospective cohort study examined patients prescribed GLP1RA who underwent outpatient endoscopy stratified by exposure at the time of endoscopy.
Comparing demographic/clinical characteristics, health care resource utilization, and costs among patients with type 2 diabetes and established atherosclerotic cardiovascular disease with and without the use of cardioprotective medications.
J Manag Care Spec Pharm
January 2025
Joslin Diabetes Center, Sequel Med Tech, Boston, MA.
Background: Type 2 diabetes (T2D) causes increased health care resource utilization (HCRU) and costs in the United States. People with T2D are more likely to have atherosclerotic cardiovascular disease (ASCVD), which is associated with significant morbidity and mortality. Medical associations recommend cardioprotective antidiabetic medications, including sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs), to reduce the risk of cardiovascular events in patients with T2D with established, or a high risk of, ASCVD, but not all eligible patients receive these medications.
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!