Effect of long-term olanzapine treatment on meal-induced insulin sensitization and on gastrointestinal peptides in female Sprague-Dawley rats.
Meal-induced insulin sensitization (MIS), an endogenous adaptive mechanism is activated post-prandially. Reduced MIS leads to diabetes, but its activation improves insulin sensitivity. MIS is preserved to single olanzapine administration, therefore we aimed to investigate the chronic effect of olanzapine on fasted-state insulin sensitivity and on MIS in female Sprague-Dawley rats. Daily food and water intake, stool and urine production and body weight were determined. The MIS was characterized by a rapid insulin sensitivity test. Fasting hepatic and peripheral insulin sensitivity were determined by a hyperinsulinaemic euglycaemic glucose clamping supplemented with radiotracer technique. Fasted and post-prandial blood samples were obtained for plasma insulin, leptin, ghrelin, amylin, GLP-1, GIP, PYY and PP determination. Adiposity was characterized by weighing intra-abdominal and inguinal fat pads. Olanzapine caused hepatic insulin resistance and a reduced metabolic clearance rate of insulin, but the MIS retained its function. Body weight and adiposity were enhanced, but olanzapine failed to increase food intake. Fasting insulin and leptin were elevated and the post-prandial reduction in ghrelin level was inhibited by olanzapine.The MIS remained functionally intact after long-term olanzapine treatment. Altered insulin, leptin and ghrelin levels indicate olanzapine-induced metabolic derangements. Pharmacological activation of MIS could potentially be exploited to treat or prevent olanzapine-induced insulin resistance.
Cera-Med Ltd, Debrecen, Hungary.
Csaba
C
Hegedűs
Department of Pharmacology and Pharmacotherapy, University of Debrecen Faculty of Medicine, Debrecen, Hungary.
Diána
D
Kovács
Department of Pharmacology and Pharmacotherapy, University of Debrecen Faculty of Medicine, Debrecen, Hungary.
Rita
R
Kiss
Department of Pharmacology and Pharmacotherapy, University of Debrecen Faculty of Medicine, Debrecen, Hungary.
Réka
R
Sári
Department of Pharmacology and Pharmacotherapy, University of Debrecen Faculty of Medicine, Debrecen, Hungary.
József
J
Németh
Department of Pharmacology and Pharmacotherapy, University of Debrecen Faculty of Medicine, Debrecen, Hungary.
Zoltán
Z
Szilvássy
Department of Pharmacology and Pharmacotherapy, University of Debrecen Faculty of Medicine, Debrecen, Hungary barna.peitl@gmail.com.
Barna
B
Peitl
D000818:Animals; D001569:Benzodiazepines / Q000008:administration & dosage*; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005768:Gastrointestinal Hormones / Q000097:blood*; D054439:Ghrelin / Q000097:blood; D007328:Insulin / Q000096:biosynthesis*; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood; D009765:Obesity / Q000097:blood; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D005768:Gastrointestinal Hormones; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D001569:Benzodiazepines; D000077152:Olanzapine
Olanzapine; ghrelin; insulin resistance; leptin; obesity