Endocrine Abstracts

Introduction: Glucocorticoids (GCs) are widely used anti-inflammatory medications that cause many metabolic side effects. Long-term treatment with GCs causes obesity and induces insulin resistance in many metabolic tissues, including adipose tissue and muscle. Factors secreted by adipose tissue, so-called adipokines, including leptin and adiponectin, also regulate the glucose-insulin axis. Obesity increases circulating leptin but decreases adiponectin levels. Despite several studies on GC regulation of adipose tissue function, mass, and distribution, the sex-specific effects of GCs have not been well elucidated. Here, we studied the effects of high-dose corticosterone (rodent GC) on glucose metabolism and circulating adipokines.

Methods: Nine-week-old male and female C57BL/6J mice were implanted with 50 mg corticosterone (Cort) or vehicle (Veh) pellets (6 animals per condition). Ad-lib blood glucose levels were measured every 2 days. Two weeks after implantation, we measured fasting glucose levels, collected blood samples for adipokine measurement, and performed an intraperitoneal glucose tolerance test (IPGTT). Data are shown as mean±SD.

Results: Corticosterone treatment increased food intake in both sexes, but increased ad-lib blood glucose levels only in male mice (Veh-male 8.2±0.3 mM, Cort-male 14.8±1.6 mM, Veh-female 7.6±0.4 mM, Cort-female 6.6±0.5 mM; P<0.001). Corticosterone strongly increased fasting plasma insulin levels in both sexes (Veh-male 50±17 pM, Cort-male 1071±438 pM, Veh-female 28±5 pM, Cort-female 1104±631 mmol/l; p_Cort<0.001), but fasting blood glucose levels of both sexes remained within normal range. Corticosterone increased fat mass and serum leptin levels in both sexes. Surprisingly, adiponectin levels were also increased. Female mice had a higher basal adiponectin/leptin ratio than male mice and corticosterone markedly reduced the ratios in both sexes (Veh-male 34±24, Cort-male 1.9±0.3, Veh-female 375±351, Cort-female 3.9±1.4; p_Sex=.035, p_Cort=.015). IPGTT showed that corticosterone treatment resulted in blunted peak glucose levels in both sexes but more pronounced in female mice.

Conclusions: Sub-chronic high-dose GC causes insulin resistance without fasting hyperglycemia in both sexes of mice, but causes remarkably high glucose levels in the ad-lib fed condition in male mice only. GCs increase fat mass and alter circulating adipokine levels in both sexes. Adipose tissue adaptation such as an increased adiponectin secretion may be a crucial initial protective mechanism against the GC-induced metabolic disturbances.