52. Antipsychotics Perturb Glucose Homeostasis by Inhibiting Hypothalamic KATP Channel Activation

Abstract

Antipsychotics are associated with high rates of obesity and type 2 diabetes. Moreover, these agents can immediately and independently of weight gain induce insulin resistance via the central nervous system (CNS). We recently demonstrated that olanzapine abolishes the ability of a CNS insulin infusion to restrain hepatic glucose production and to suppress feeding in rodents. Across rodents and humans, the ATP-sensitive potassium (KATP) channel is a critical metabolic sensor downstream of hypothalamic insulin signaling in maintenance of energy and glucose homeostasis. Here, we examined whether olanzapine inhibits central KATP channels to disrupt glucose metabolism.