Exercise Protects Against Olanzapine-Induced Hyperglycemia in Male C57BL/6J Mice

Olanzapine is a widely prescribed antipsychotic drug. While effective in reducing psychoses, treatment with olanzapine causes rapid increases in blood glucose. We wanted to determine if a single bout of exercise, immediately prior to treatment, would attenuate the olanzapine-induced rise in blood glucose and if this occurred in an IL-6 dependent manner. We found that exhaustive, but not moderate exercise, immediately prior to treatment, prevented olanzapine-induced hyperglycemia and this occurred in parallel with increases in serum IL-6. To determine if IL-6 was involved in the mechanisms through which exhaustive exercise protected against olanzapine-induced hyperglycemia several additional experiments were completed. Treatment with IL-6 (3 ng/g bw, IP) alone did not protect against olanzapine-induced increases in blood glucose. The protective effects of exhaustive exercise against olanzapine-induced increases in blood glucose were intact in whole body IL-6 knockout mice. Similarly, treating mice with an IL-6 neutralizing antibody prior to exhaustive exercise did not negate the protective effect of exercise against olanzapine-induced hyperglycemia. Our findings provide evidence that a single bout of exhaustive exercise protects against acute olanzapine-induced hyperglycemia and that IL-6 is neither sufficient, nor required for exercise to protect against increases in blood glucose with olanzapine treatment.