| Autor: |
Katrine D. Galsgaard, Emilie Elmelund, Christian D. Johansen, Anna B. Bomholt, Hüsün S. Kizilkaya, Frederik Ceutz, Jenna E. Hunt, Hannelouise Kissow, Marie Winther-Sørensen, Charlotte M. Sørensen, Thomas Kruse, Jesper F. Lau, Mette M. Rosenkilde, Cathrine Ørskov, Christina Christoffersen, Jens J. Holst, Nicolai J. Wewer Albrechtsen |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Molecular Metabolism, Vol 66, Iss , Pp 101639- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2212-8778 |
| DOI: |
10.1016/j.molmet.2022.101639 |
| Popis: |
Objective: Treatment with glucagon receptor antagonists (GRAs) reduces blood glucose but causes dyslipidemia and accumulation of fat in the liver. We investigated the acute and chronic effects of glucagon on lipid metabolism in mice. Methods: Chronic effects of glucagon receptor signaling on lipid metabolism were studied using oral lipid tolerance tests (OLTTs) in overnight fasted glucagon receptor knockout (Gcgr−/−) mice, and in C57Bl/6JRj mice treated with a glucagon receptor antibody (GCGR Ab) or a long-acting glucagon analogue (GCGA) for eight weeks. Following treatment, liver tissue was harvested for RNA-sequencing and triglyceride measurements. Acute effects were studied in C57Bl/6JRj mice treated with a GRA or GCGA 1 h or immediately before OLTTs, respectively. Direct effects of glucagon on hepatic lipolysis were studied using isolated perfused mouse liver preparations. To investigate potential effects of GCGA and GRA on gastric emptying, paracetamol was, in separate experiments, administered immediately before OLTTs. Results: Plasma triglyceride concentrations increased 2-fold in Gcgr−/− mice compared to their wild-type littermates during the OLTT (P = 0.001). Chronic treatment with GCGR Ab increased, whereas GCGA treatment decreased, plasma triglyceride concentrations during OLTTs (P |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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