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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.

Olanzapine (OLZ) is a second-generation antipsychotic that is used to treat schizophrenia but also causes acute hyperglycemia. This study aimed to determine if the ablation of AMPK b1-containing complexes potentiates acute OLZ-induced metabolic dysfunction and if the activation of AMPK b1 suppresses these effects. Female AMPK b1 2/2 or wild-type (WT) control mice were treated with OLZ, and changes in blood glucose, serum and liver metabolites, whole-body fuel oxidation, and pyruvate-induced increases in blood glucose were measured. Additionally, WT mice were cotreated with OLZ and A769662, a specific AMPK b1 activator, and we determined if cotreatment protected against acute, OLZ-induced metabolic dysfunction. OLZ-induced increases in blood glucose were exacerbated in AMPK b1 2/2 mice compared with WT mice, and this was paralleled by greater OLZ-induced increases in markers of liver glucose production, such as pyruvate tolerance, serum glucagon, and glucagon responsiveness. Cotreatment with A769662 attenuated OLZ-induced increases in blood glucose, serum nonesterified fatty acid, and glycerol. Furthermore, this effect was absent in AMPK b1 2/2 mice, consistent with A769662's specificity for the AMPK b1 subunit. Reductions in AMPK activity potentiate the effects of acute OLZ treatment on blood glucose, whereas specifically targeting AMPK b1-containing complexes is sufficient to protect against OLZ-induced hyperglycemia.

Nongovernmental organizations contribute to the securement and management of protected areas, but it is not well known how their lands compare to government protected areas or the effectiveness of different land acquisition strategies. Using data from the International Union for Conservation of Nature and BirdLife International, we estimated total and at-risk terrestrial native vertebrate species richness in southern Canada among ( i) private protected areas secured by the Nature Conservancy of Canada (NCC), government protected areas, and randomly sampled land; ( ii) conservation agreements and fee simple (directly acquired) NCC properties; and ( iii) purchased or donated fee simple properties. Controlling for property size and ecoregion, NCC protected areas were predicted to be in areas with 6% and 13% more total and at-risk species than randomly sampled land and 4% and 6% more total and at-risk species than government protected areas. Within NCC protected areas, conservation agreements were predicted to be in areas with 2% and 4% more total and at-risk species than fee simple properties, but purchased properties had similar numbers of total and at-risk species as donated properties. Although we caution that diversity estimates were based on course-grained range maps, our findings suggest that private protected areas are important in conserving biodiversity.