In male rats, the ability of central insulin to suppress glucose production is impaired by olanzapine, whereas glucose uptake is left intact.
J Psychiatry Neurosci
; 42(6): 424-431, 2017 11.
Article
en En
| MEDLINE
| ID: mdl-29083297
ABSTRACT
BACKGROUND:
Insulin receptors are widely expressed in the brain and may represent a crossroad between metabolic and cognitive disorders. Although antipsychotics, such as olanzapine, are the cornerstone treatment for schizophrenia, they are associated with high rates of type 2 diabetes and lack efficacy for illness-related cognitive deficits. Historically, this risk of diabetes was attributed to the weight gain propensity of antipsychotics, but recent work suggests antipsychotics can have weight-independent diabetogenic effects involving unknown brain-mediated mechanisms. Here, we examined whether antipsychotics disrupt central insulin action, hypothesizing that olanzapine would impair the well-established ability of central insulin to supress hepatic glucose production.METHODS:
Pancreatic euglycemic clamps were used to measure glucose kinetics alongside a central infusion of insulin or vehicle into the third ventricle. Male rats were pretreated with olanzapine or vehicle per our established model of acute olanzapine-induced peripheral insulin resistance. Groups included (central-peripheral) vehicle-vehicle (n = 11), insulin-vehicle (n = 10), insulin-olanzapine (n = 10) and vehicle-olanzapine (n = 8).RESULTS:
There were no differences in peripheral glucose or insulin levels. Unexpectedly, we showed that central insulin increased glucose uptake, and this effect was not perturbed by olanzapine. We replicated suppression of glucose production by insulin (clamp relative to basal 77.9% ± 13.1%, all p < 0.05), an effect abolished by olanzapine (insulin-olanzapine 7.7% ± 14%).LIMITATIONS:
This study used only male rats and an acute dose of olanzapine.CONCLUSION:
To our knowledge, this is the first study suggesting olanzapine may impair central insulin sensing, elucidating a potential mechanism of antipsychotic-induced diabetes and opening avenues of investigation related to domains of schizophrenia psychopathology.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Antipsicóticos
/
Benzodiazepinas
/
Glucosa
/
Insulina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Psychiatry Neurosci
Asunto de la revista:
NEUROLOGIA
/
PSIQUIATRIA
Año:
2017
Tipo del documento:
Article