mProX™ Human GLP1R Stable Cell Line

Wright SC, et al. "GLP-1R signaling neighborhoods associate with the susceptibility to adverse drug ." Nature communications, 2023.
G protein-coupled receptors play a significant role as drug targets by activating signaling transducers in various cellular compartments. Efficiently differentiating between therapeutic signaling and signals that lead to adverse events is crucial for rational drug design. While the glucagon-like peptide-1 receptor (GLP-1R) is a recognized target for treating diabetes and obesity, drugs targeting this receptor often result in adverse events. Utilizing newly developed biosensors, the authors investigate GLP-1R's potential to activate 15 pathways in 4 cellular compartments. Their results show that modifications made to improve the efficacy, potency, and safety of GLP-1R agonists have a selective impact on pathways and compartments. Through comparative structure analysis, time-lapse microscopy, and phosphoproteomics, the authors demonstrate distinctive signaling patterns for GLP-1R agonists at the levels of receptor conformation, functional selectivity, and compartmental bias. These findings establish a link between signaling neighborhoods and distinct cellular outcomes and clinical consequences, providing valuable insights into rational drug design.
Pubmed: 37813859   DOI: 10.1038/s41467-023-41893-4

Ahmad K, et al. "Therapeutic application of natural compounds for skeletal muscle-associated ." Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2023.
Skeletal muscle (SM) is a crucial player in energy and glucose metabolism by regulating insulin sensitivity, glucose uptake, and blood glucose homeostasis. Its impaired functioning has been closely linked to various diseases, particularly type 2 diabetes (T2D). SM's insulin resistance may stem from deficiencies in insulin receptor tyrosine kinase, insulin receptor substrate 1, phosphoinositide 3-kinase, and AKT pathways. This review provides a brief overview of SM myogenesis and its pivotal role in T2D's insulin resistance. It also delves into potential SM-related therapeutic targets for T2D, such as DPP4, PTB1B, SGLT, PPARgamma, and GLP-1R, as well as their potential natural compound modulators/inhibitors. This study emphasizes the importance of SM in metabolic disorders and the potential of natural compounds in targeting T2D-associated SM targets, providing valuable insights for the development of future anti-diabetic drugs. The authors believe that this review can enhance scientists' understanding and knowledge of T2D therapies.
Pubmed: 37812896   DOI: 10.1016/j.biopha.2023.115642