title: Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice.
abstract: Steroid-induced diabetes is the most common form of drug-induced hyperglycemia. Therefore, metabolic and immunological alterations associated with chronic oral corticosterone were investigated using male nonobese diabetic mice. Three weeks after corticosterone delivery, there was reduced sensitivity to insulin action measured by insulin tolerance test. Body composition measurements revealed increased fat mass and decreased lean mass. Overt hyperglycemia (>250 mg/dL) manifested 6 weeks after the start of glucocorticoid administration, whereas 100% of the mice receiving the vehicle control remained normoglycemic. This phenotype was fully reversed during the washout phase and readily reproducible across institutions. Relative to the vehicle control group, mice receiving corticosterone had a significant enhancement in pancreatic insulin-positive area, but a marked decrease in CD3+cell infiltration. In addition, there were striking increases in both citrate synthase gene expression and enzymatic activity in skeletal muscle of mice in the corticosterone group relative to vehicle control. Moreover, glycogen synthase expression was greatly enhanced, consistent with elevations in muscle glycogen storage in mice receiving corticosterone. Corticosterone-induced hyperglycemia, insulin resistance, and changes in muscle gene expression were all reversed by the end of the washout phase, indicating that the metabolic alterations were not permanent. Thus, male nonobese diabetic mice allow for translational studies on the metabolic and immunological consequences of glucocorticoid-associated interventions in a mouse model with genetic susceptibility to autoimmune disease.
authors.affiliation: Laboratory of Islet Biology and Inflammation, Pennington Biomedical Research Center, Baton Rouge, Louisiana.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Burke
authors.affiliation: Laboratory of Islet Biology and Inflammation, Pennington Biomedical Research Center, Baton Rouge, Louisiana; Skeletal Muscle Metabolism Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana.
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Batdorf
authors.affiliation: Department of Surgery, Graduate School of Medicine, University of Tennessee Health Science Center, Knoxville, Tennessee.
authors.forename: Adrianna E
authors.initials: AE
authors.lastname: Eder
authors.affiliation: Department of Surgery, Graduate School of Medicine, University of Tennessee Health Science Center, Knoxville, Tennessee.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Karlstad
authors.affiliation: Cell Biology and Bioimaging Core Facility, Pennington Biomedical Research Center, Baton Rouge, Louisiana.
authors.forename: David H
authors.initials: DH
authors.lastname: Burk
authors.affiliation: Skeletal Muscle Metabolism Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Noland
authors.affiliation: Ubiquitin Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana.
authors.forename: Z Elizabeth
authors.initials: ZE
authors.lastname: Floyd
authors.affiliation: Laboratory of Islet Biology and Inflammation, Pennington Biomedical Research Center, Baton Rouge, Louisiana. Electronic address: jason.collier@pbrc.edu.
authors.forename: J Jason
authors.initials: JJ
authors.lastname: Collier
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D017252:CD3 Complex / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy* / Q000473:pathology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology; D008297:Male; D016688:Mice, Inbred NOD; D008954:Models, Biological; D010641:Phenotype; D051381:Rats; D013851:Thinness / Q000097:blood / Q000235:genetics
chemical_list: D017252:CD3 Complex; D007328:Insulin; D006003:Glycogen; D002950:Citrate (si)-Synthase; D006006:Glycogen Synthase; D003345:Corticosterone