GLP1 Receptor Agonism Protects Against Acute Olanzapine Induced Hyperglycemia.

GLP1 Receptor Agonism Protects Against Acute Olanzapine Induced Hyperglycemia. Am J Physiol Endocrinol Metab. 2020 Oct 05;: Authors: Medak KD, Shamshoum H, Peppler WT, Wright DC Abstract Olanzapine is a second-generation antipsychotic (SGA) used in the treatment of schizophrenia and a number of off-label conditions. While effective in reducing psychoses, acute olanzapine treatment causes hyperglycemia. Pharmacological agonists of the glucagon-like peptide-1 (GLP1) receptor have been shown to offset weight-gain associated with chronic SGA administration. It is not known if GLP-1 receptor agonism would mitigate the acute metabolic side effects of SGAs. Within this context, we sought to determine if pharmacological targeting of the GLP1 receptor would be sufficient to protect against acute olanzapine induced impairments in glucose and lipid homeostasis. Male C57BL/6J mice were treated with olanzapine and/or the GLP-1 receptor agonists liraglutide or exendin 4 and the blood glucose response measured. We found that liraglutide or exendin 4 completely protected male mice against olanzapine-induced hyperglycemia in parallel with increases in circulating insulin (liraglutide, exendin 4) and reductions in glucagon (liraglutide only). In additional experiments, female mice, which are protected from acute olanzapine-induced hyperglycemia, displayed hyperglycemia, increases in glucagon and reductions in insulin when treated with olanzapine and t...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research