| First Author | Shamshoum H | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 12 | Pages | 14010-14021 |
| PubMed ID | 31581839 | Mgi Jnum | J:297682 |
| Mgi Id | MGI:6472489 | Doi | 10.1096/fj.201901820R |
| Citation | Shamshoum H, et al. (2019) AMPK beta1 activation suppresses antipsychotic-induced hyperglycemia in mice. FASEB J 33(12):14010-14021 |
| abstractText | 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 beta1-containing complexes potentiates acute OLZ-induced metabolic dysfunction and if the activation of AMPK beta1 suppresses these effects. Female AMPK beta1(-/-) 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 beta1 activator, and we determined if cotreatment protected against acute, OLZ-induced metabolic dysfunction. OLZ-induced increases in blood glucose were exacerbated in AMPK beta1(-/-) 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 beta1(-/-) mice, consistent with A769662's specificity for the AMPK beta1 subunit. Reductions in AMPK activity potentiate the effects of acute OLZ treatment on blood glucose, whereas specifically targeting AMPK beta1-containing complexes is sufficient to protect against OLZ-induced hyperglycemia.-Shamshoum, H., Medak, K. D., Townsend, L. K., Ashworth, K. E., Bush, N. D., Hahn, M. K., Kemp, B. E., Wright, D. C. AMPK beta1 activation suppresses antipsychotic-induced hyperglycemia in mice. |
