Journal Article

Glucose Kinetics in the Collagen-Induced Arthritis Model: An All-in-One Model to Assess Both Efficacy and Metabolic Side Effects of Glucocorticoids

van der Vleuten, Monique A. J., van Doorn, Cindy, van Lierop, Marie-Jose C., Dokter, Wim H. A., Grefhorst, Aldo, Koenders, Marije I., Laskewitz, Anke J., Schouten, Annelies E., Bastiaanssen, Ellen A. J., Toonen, Erik J. M., Bleeker, Aycha, Ballak, Dov B., Groen, Albert K., van Dijk, Theo H.

2014

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Animal models / Animals / Anti-inflammatory agents / Arthritis / Arthritis, Experimental - blood / Arthritis, Experimental - drug therapy / Arthritis, Experimental - metabolism / Biology and Life Sciences / Blood / Blood glucose / Blood Glucose - metabolism / Collagen / Complications and side effects / Diabetes / Disease Models, Animal / Drug dosages / Drugs / Effectiveness / Glucocorticoids / Glucocorticoids - adverse effects / Glucocorticoids - pharmacology / Glucocorticoids - therapeutic use / Glucose / Hyperglycemia / Inflammation / Insulin / Insulin resistance / Insulin secretion / Internal medicine / Kinetics / Laboratories / Male / Medicine / Medicine and Health Sciences / Metabolism / Mice / Pediatrics / Prednisolone / Prednisolone - adverse effects / Prednisolone - pharmacology / Prednisolone - therapeutic use / Research and Analysis Methods / Rheumatoid arthritis / Rheumatoid factor / Rodents / Secretion / Side effects / Steroids (Organic compounds) / Studies