Glucagon-like peptide-1 (GLP-1)-based diabetes therapy is increasingly used in the treatment of type 2 diabetes. Two GLP-1 analogs, liraglutide and exenatide, have been approved for clinical use and act as agonists of the GLP-1 receptor (GLP-1R), a member of the glucagon receptor family of G protein-coupled receptors (GPCRs) (1). Also, the clinical effect of DiPeptidyl Peptidase-4 (DPP-4) inhibitors is at least partially resulting from an increased level of active GLP-1 (2). The unambiguous identification of GLP-1R-expressing cells in humans and animal species constitutes critically important knowledge for fully understanding the pharmacological effects of GLP-1R agonists, both those associated with the documented clinical benefits as well as any potential undesired effects of treatment. The GLP-1R was cloned in 1992 (3). Preceding that, the receptor was identified in numerous cell types and organs, most obviously the pancreatic -cell but also in rat lung and brain by studies using either ligand binding or functional assays (4, 5). After the receptor was cloned, RT-PCR and in situ hybridization were used to report tissue distribution, and the receptor was located in the intestine, stomach, kidney, lungs, heart, and brain (6, 7). Later studies have used Western blotting and immunohistochemistry to identify the exact cellular localization of the receptor. Using such techniques, the receptor has been identified in mouse cardiomyocytes and smooth muscle cells in the heart, and in porcine tubular cells in the kidney (8, 9). Human GLP-1R expression has been mapped by in situ ligand binding across a wide range of both normal and tumor tissues (10). In this issue of Endocrinology, Panjwani et al. (11) reports new knowledge about the mechanism of action of GLP-1 analogs in atherosclerosis and hepatic steatosis and challenges some GLP-1R expression data in macrophages and hepatocytes that have previously been published. When Panjwani et al. (11) could not identify GLP-1R mRNA on macrophages or isolated hepatocytes despite previous reports of such localization, they did a careful Western blotting characterization of three commercially available polyclonal antibodies (PAbs) against the GLP-1R that are commonly used for Western blotting. They used mouse wild-type lung tissue that has a very high expression of GLP-1R as a positive control and lung tissue from GLP-1R / mice as a negative control. They also employed a very thorough procedure with immunoprecipitation in an attempt to increase the sensitivity of the analysis but found no GLP-1R-specific expression. The authors conclude that multiple commercially available GLP-1R antibodies do not detect authentic GLP-1R protein, even using optimally enhanced methods. This technical difficulty at first glance seems to have little bearing on aspects of GLP-1 biology unrelated to the scope of the article; however, on further consideration, it brings into focus a potentially serious problem with the validity of any GLP-1R expression data generated through the use of antibodies. Adding to the complexity, for some GLP-1R-containing organs, markedly different GLP-1R expression patterns have been reported between human and rodent species (10, 12). Rodent thyroid C-cells express much higher levels of GLP-1R than primates (10, 12), and there may be an important species difference, where the GLP-1R in the rodent thyroid is important for the high bone turnover in those species but less important in humans (13, 14). In the lung, the number of GLP1R-expressing cells and the receptor density is much