Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice

Susan J. Burke, Heidi M. Batdorf, Adrianna E. Eder, Michael Karlstad, David H. Burk, Robert C. Noland, Z. Elizabeth Floyd, J. Jason Collier

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)614-626
Number of pages13
JournalAmerican Journal of Pathology
Volume187
Issue number3
DOIs
StatePublished - Mar 1 2017

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Inbred NOD Mouse
Corticosterone
Hyperglycemia
Oral Administration
Insulin Resistance
Glucocorticoids
Insulin
Gene Expression
Citrate (si)-Synthase
Muscles
Glycogen Synthase
Genetic Predisposition to Disease
Body Composition
Glycogen
Autoimmune Diseases
Skeletal Muscle
Fats
Steroids
Phenotype
Control Groups

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice. / Burke, Susan J.; Batdorf, Heidi M.; Eder, Adrianna E.; Karlstad, Michael; Burk, David H.; Noland, Robert C.; Floyd, Z. Elizabeth; Collier, J. Jason.

In: American Journal of Pathology, Vol. 187, No. 3, 01.03.2017, p. 614-626.

Research output: Contribution to journalArticle

Burke, Susan J. ; Batdorf, Heidi M. ; Eder, Adrianna E. ; Karlstad, Michael ; Burk, David H. ; Noland, Robert C. ; Floyd, Z. Elizabeth ; Collier, J. Jason. / Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice. In: American Journal of Pathology. 2017 ; Vol. 187, No. 3. pp. 614-626.
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