Oral Corticosterone Administration Reduces Insulitis but Promotes Insulin Resistance and Hyperglycemia in Male Nonobese Diabetic Mice
| Autor: | Robert C. Noland, Heidi M. Batdorf, Michael D. Karlstad, Adrianna E. Eder, J. Jason Collier, Susan J. Burke, Z. Elizabeth Floyd, David H. Burk |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty CD3 Complex medicine.medical_treatment Administration Oral Citrate (si)-Synthase Biology Models Biological Gene Expression Regulation Enzymologic Pathology and Forensic Medicine Islets of Langerhans 03 medical and health sciences chemistry.chemical_compound Insulin resistance Thinness Mice Inbred NOD Corticosterone Internal medicine Diabetes mellitus medicine Animals Insulin Glycogen synthase Glycogen Insulin tolerance test Regular Article medicine.disease Rats Glycogen Synthase Phenotype 030104 developmental biology Endocrinology chemistry Hyperglycemia Body Composition biology.protein Insulin Resistance Insulitis |
| Zdroj: | The American Journal of Pathology. 187:614-626 |
| ISSN: | 0002-9440 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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