1908-P: Glucagon Receptor Expression Evaluated by Antibody-Dependent and -Independent Approaches
| العنوان: | 1908-P: Glucagon Receptor Expression Evaluated by Antibody-Dependent and -Independent Approaches |
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| المؤلفون: | Reza Rafiolsadat Serizawa, Katrine D. Galsgaard, Reidar Albrechtsen, Jens J. Holst, Cathrine Ørskov, Lise Lotte Gluud, Jens Pedersen, Charlotte Mehlin Sorensen, Sasha A.S. Kjeldsen, Marie Winther-Soerensen, Nicolai J. Wewer Albrechtsen |
| المصدر: | Diabetes. 69 |
| بيانات النشر: | American Diabetes Association, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | medicine.medical_specialty, Endocrinology, biology, Chemistry, Endocrinology, Diabetes and Metabolism, Internal medicine, Internal Medicine, biology.protein, medicine, Antibody, Glucagon receptor |
| الوصف: | Glucagon regulates metabolic functions through the glucagon receptor (GCGR). Agonists as well as antagonists of GCGR are evaluated as treatments of diabetes and obesity. To understand the role of glucagon, knowledge of GCGR localization is important but limited. Twelve commercially available GCGR antibodies were evaluated using HEK293 cells transfected with mouse or human GCGR cDNA transcripts. Eleven of the 12 GCGR antibodies showed staining of GCGR protein from both species, but not in cells transfected with a scrambled vector. Several of the antibodies stained liver sections from both GCGR+/+ and GCGR-/- mice. Staining was absent in fat and muscle tissues but present in the distal tubuli of the kidney. Two antibodies did not react with tissue from GCGR-/- and were further evaluated by western blotting of GCGR transfected cells. Bands corresponding to the predicted size of the GCGR (62kDa) were identified but larger bands were also observed. Liver tissue from healthy subjects and individuals with nonalcoholic steatohepatitis (NASH) was stained using same GCGR antibodies and based on qualitative intensities GCGR staining did not seem to vary between healthy and NASH liver sections. We used autoradiography to confirm the immunohistochemistry findings. In mice injected with 125I-labeled glucagon, grains were found in the liver and in the distal tubuli of the kidney, whereas fat and muscle sections were negative. To investigate the role of renal GCGR’s, we infused glucagon (1µg) in rats with and without blockade of the GLP-1 receptor (GLP-1R) (Exendin 9-39). Glucagon increased diuresis and renal blood flow, but not blood pressure, in a GLP-1R dependent manner. Urea excretion was numerically increased by glucagon (P=0.08). In conclusion, glucagon receptor localization is challenging due to the lack of suitable commercially available GCGR antibodies. The actions of glucagon on renal parameters may be mediated by the GLP-1R. Glucagon’s role in kidney physiology needs further investigation. Disclosure S. Kjeldsen: None. K.D. Galsgaard: None. M. Winther-Soerensen: None. R. Serizawa: None. J. Pedersen: None. C. Orskov: None. R. Albrechtsen: None. C.M. Sorensen: None. L. Gluud: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S, Novo Nordisk Foundation. Speaker’s Bureau; Self; Merck Sharp & Dohme Corp. Funding Novo Nordisk Foundation (NNF19OC0055001) |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::df2dbe97a5430728c8387b0c1cb6d2cbTest https://doi.org/10.2337/db20-1908-pTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi...........df2dbe97a5430728c8387b0c1cb6d2cb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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