At therapeutic concentrations, olanzapine does not affect basal or insulin-stimulated glucose transport in 3T3-L1 adipocytes.
The newer, atypical antipsychotic drugs have improved the treatment of schizophrenia and are widely used. A disadvantage is that they increase food intake, promote weight gain and may facilitate development of diabetes. The mechanism of the latter effect is controversial. A possible interaction of these drugs with glucose transporters has been proposed: peripheral insulin resistance may develop if these drugs inhibited glucose transport in cells which express the insulin responsive glucose transporter, GLUT4, i.e., muscle and adipocytes. To test this hypothesis, we incubated 3T3-L1 adipocytes, which express GLUT1 and GLUT4, with the atypical antipsychotic drug olanzapine for 1 or 20 h and then measured basal and insulin-stimulated glucose transport. The doses of olanzapine tested (70 nM and 350 nM) encompass and exceed maximal steady-state concentrations of the drug in plasma of patients maintained on maximal recommended doses (20 mg QD) of olanzapine. A maximally stimulating insulin concentration (100 nM) accelerated glucose transport 10- to 15-fold in 3T3-L1 adipocytes, and the half-maximally stimulating insulin dose was 0.4 nM. Olanzapine (70 or 350 nM) did not affect basal or insulin-stimulated glucose transport following 1 or 20 h drug treatment at any insulin concentration tested. The data do not support the hypothesis that olanzapine at therapeutically relevant concentrations may cause peripheral insulin resistance by direct interaction with the insulin responsive glucose transport system.
Robinson
Katherine A
KA
Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, CSB 823, P.O.Box 250624, Charleston, SC 29425, USA.
Yacoub Wasef
Sherif Z
SZ
Buse
Maria G
MG
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D000077152:Olanzapine; D013997:Time Factors
D014150:Antipsychotic Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D001569:Benzodiazepines; D003847:Deoxyglucose; D005947:Glucose; D000077152:Olanzapine