title: Chronic prednisolone treatment reduces hepatic insulin sensitivity while perturbing the fed-to-fasting transition in mice.
abstract: Chronic glucocorticoid use for treatment of inflammatory diseases is accompanied by severe side effects in humans (e.g. hyperglycemia and insulin resistance). The present studies were conducted to characterize consequences of chronic treatment with the synthetic glucocorticoid prednisolone on insulin sensitivity and blood glucose kinetics in mice. Prednisolone treatment increased fasting blood glucose and plasma insulin concentrations, but this apparently reduced insulin sensitivity could not be confirmed in hyperinsulinemic euglycemic clamp studies. Therefore, a novel method to study whole body glucose kinetics was used. This method revealed that prednisolone-treated mice show an increased hepatic glucose production (HGP). The increased HGP was accompanied by elevated plasma insulin concentrations, indicating reduced insulin sensitivity of hepatic glucose metabolism in prednisolone-treated mice. Compared with vehicle, prednisolone-treated mice had lower blood glucose concentrations, higher plasma free fatty acids, and higher plasma fibroblast growth factor-21 concentrations in the fed condition, i.e. mimicking a fasting situation. Next, the effects of 24-h fasting on energy metabolism were studied. Compared with controls, fasted prednisolone-treated mice had higher blood glucose concentrations and lower plasma beta-hydroxybutyrate concentrations. In conclusion, these results indicate that chronic prednisolone treatment reduces insulin sensitivity of HGP, induces a fasting-like phenotype in fed mice, and perturbs the fed-to-fasting transition.
authors.affiliation: Department of Pediatrics, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen, RB Groningen, The Netherlands.
authors.forename: Anke J
authors.initials: AJ
authors.lastname: Laskewitz
authors.forename: Theo H
authors.initials: TH
authors.lastname: van Dijk
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Bloks
authors.forename: Dirk-Jan
authors.initials: DJ
authors.lastname: Reijngoud
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: van Lierop
authors.forename: Wim H
authors.initials: WH
authors.lastname: Dokter
authors.forename: Folkert
authors.initials: F
authors.lastname: Kuipers
authors.forename: Albert K
authors.initials: AK
authors.lastname: Groen
authors.forename: Aldo
authors.initials: A
authors.lastname: Grefhorst
mesh_terms: D000465:Algorithms; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects; D005215:Fasting / Q000097:blood / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism* / Q000493:pharmacokinetics; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000235:genetics; D011239:Prednisolone / Q000494:pharmacology*; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D047493:PPAR alpha; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D011239:Prednisolone; D005947:Glucose