| Autor: |
Toonen EJ; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands., Laskewitz AJ; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., van Dijk TH; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Bleeker A; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Grefhorst A; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands., Schouten AE; Department of Immune Therapeutics, MSD Research Laboratories, Oss, The Netherlands., Bastiaanssen EA; Department of Immune Therapeutics, MSD Research Laboratories, Oss, The Netherlands., Ballak DB; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands., Koenders MI; Department of Experimental Rheumatology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Centre, Nijmegen, The Netherlands., van Doorn C; Department of Immune Therapeutics, MSD Research Laboratories, Oss, The Netherlands., van der Vleuten MA; Department of Immune Therapeutics, MSD Research Laboratories, Oss, The Netherlands., van Lierop MJ; Department of Immune Therapeutics, MSD Research Laboratories, Oss, The Netherlands., Groen AK; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Dokter WH; Department of Immune Therapeutics, MSD Research Laboratories, Oss, The Netherlands. |
| Abstrakt: |
Prednisolone and other glucocorticoids (GCs) are potent anti-inflammatory drugs, but chronic use is hampered by metabolic side effects. Therefore, there is an urgent medical need for improved GCs that are as effective as classical GCs but have a better safety profile. A well-established model to assess anti-inflammatory efficacy is the chronic collagen-induced arthritis (CIA) model in mice, a model with features resembling rheumatoid arthritis. Models to quantify undesired effects of glucocorticoids on glucose kinetics are less well-established. Recently, we have described a model to quantify basal blood glucose kinetics using stably-labeled glucose. In the present study, we have integrated this blood glucose kinetic model in the CIA model to enable quantification of both efficacy and adverse effects in one animal model. Arthritis scores were decreased after treatment with prednisolone, confirming the anti-inflammatory properties of GCs. Both inflammation and prednisolone induced insulin resistance as insulin secretion was strongly increased whereas blood glucose concentrations and hepatic glucose production were only slightly decreased. This insulin resistance did not directly resulted in hyperglycemia, indicating a highly adaptive compensatory mechanism in these mice. In conclusion, this 'all-in-one' model allows for studying effects of (novel) GC compounds on the development of arthritis and glucose kinetics in a single animal. This integrative model provides a valuable tool for investigating (drug-induced) metabolic dysregulation in an inflammatory setting. |
