In male rats, the ability of central insulin to suppress glucose production is impaired by olanzapine, whereas glucose uptake is left intact.

Journal of Psychiatry & Neuroscience : JPN
Chantel KowalchukMargaret Hahn

Abstract

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. 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). There were no differences in peripheral glucose...Continue Reading

Citations

Jan 13, 2021·Schizophrenia Research·Chantel KowalchukMargaret K Hahn
Oct 6, 2020·American Journal of Physiology. Endocrinology and Metabolism·Kyle D MedakDavid C Wright
Oct 1, 2019·Expert Opinion on Drug Safety·Wade MarteeneDan Siskind
Dec 19, 2020·Frontiers in Psychiatry·Heidi N BoydaAlasdair M Barr
Jun 4, 2019·Neuropharmacology·Sri Mahavir AgarwalMargaret Hahn
Jul 4, 2018·American Journal of Physiology. Endocrinology and Metabolism·Chantel KowalchukMargaret K Hahn
Jul 12, 2019·Journal of Psychopharmacology·Jacobi I CunninghamMark Namchuk
May 10, 2018·Frontiers in Endocrinology·Andrea Del CampoLeonel E Rojo
Mar 16, 2021·Frontiers in Endocrinology·Jessica W Y YuenAlasdair M Barr
Aug 31, 2021·Acta Psychiatrica Scandinavica·Emily SmithSri Mahavir Agarwal

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