BACKGROUND: Olanzapine is a second generation antipsychotic. A common side effect in humans is weight gain, but the mechanisms are mostly unknown. AIM: To study the effects of subchronic olanzapine treatment on body weight, fasting plasma glucose (FPG), fasting insulin (FINS), C-peptide, insulin sensitivity index (ISI), and expression of glucose transporter 2 (GLUT2) in rat pancreatic β cells. MATERIALS AND METHODS: Female Sprague-Dawley rats were randomly divided into two groups: the olanzapine-treated group and the control group (each n = 8). Rats in the olanzapine-treated group intragastrically received olanzapine 5 mg/kg/day for 28 days; the rats in the control group received the same volume of vehicle. FPG and body weight were measured on the 1st, 7th, 14th and 28th day. FINS and C-peptide were measured using immunoradiometric assays at baseline and on the 28th day. GLUT2 mRNA and protein expressions in pancreatic β cells were analyzed by RT-PCR and western blot. RESULTS: Olanzapine-treated rats had higher body weight (227.4 ± 8.9 vs. 211.0 ± 9.9 g), FPG (5.86 ± 0.42 vs. 4.24 ± 0.29 mmol/L), FINS (17.34 ± 3.64 vs. 10.20 ± 1.50 µIU/mL), and C-peptide (0.154 ± 0.027 vs. 0.096 ± 0.009 ng/mL) than those in controls (all P < 0.05) at the 28th day. Pancreatic β cells of the olanzapine-treated group showed lower ISI (-4.60 ± 0.23 vs. -3.76 ± 0.20) and GLUT2 levels (mRNA: 1.12 ± 0.02 vs. 2.00 ± 0.03; protein: 0.884 ± 0.134 vs. 1.118 ± 0.221) than those in controls (all P < 0.05). CONCLUSIONS: Subchronic olanzapine treatment inhibited expression of GLUT2 in rat pancreatic β cells. Therefore, it may disturb glucose metabolism via the insulin resistance of β cells, but confirmation in humans is needed.
BACKGROUND:Olanzapine is a second generation antipsychotic. A common side effect in humans is weight gain, but the mechanisms are mostly unknown. AIM: To study the effects of subchronic olanzapine treatment on body weight, fasting plasma glucose (FPG), fasting insulin (FINS), C-peptide, insulin sensitivity index (ISI), and expression of glucose transporter 2 (GLUT2) in ratpancreatic β cells. MATERIALS AND METHODS: Female Sprague-Dawley rats were randomly divided into two groups: the olanzapine-treated group and the control group (each n = 8). Rats in the olanzapine-treated group intragastrically received olanzapine 5 mg/kg/day for 28 days; the rats in the control group received the same volume of vehicle. FPG and body weight were measured on the 1st, 7th, 14th and 28th day. FINS and C-peptide were measured using immunoradiometric assays at baseline and on the 28th day. GLUT2 mRNA and protein expressions in pancreatic β cells were analyzed by RT-PCR and western blot. RESULTS:Olanzapine-treated rats had higher body weight (227.4 ± 8.9 vs. 211.0 ± 9.9 g), FPG (5.86 ± 0.42 vs. 4.24 ± 0.29 mmol/L), FINS (17.34 ± 3.64 vs. 10.20 ± 1.50 µIU/mL), and C-peptide (0.154 ± 0.027 vs. 0.096 ± 0.009 ng/mL) than those in controls (all P < 0.05) at the 28th day. Pancreatic β cells of the olanzapine-treated group showed lower ISI (-4.60 ± 0.23 vs. -3.76 ± 0.20) and GLUT2 levels (mRNA: 1.12 ± 0.02 vs. 2.00 ± 0.03; protein: 0.884 ± 0.134 vs. 1.118 ± 0.221) than those in controls (all P < 0.05). CONCLUSIONS: Subchronic olanzapine treatment inhibited expression of GLUT2 in ratpancreatic β cells. Therefore, it may disturb glucose metabolism via the insulin resistance of β cells, but confirmation in humans is needed.
Authors: Cristen J Willer; Lori L Bonnycastle; Karen N Conneely; William L Duren; Anne U Jackson; Laura J Scott; Narisu Narisu; Peter S Chines; Andrew Skol; Heather M Stringham; John Petrie; Michael R Erdos; Amy J Swift; Sareena T Enloe; Andrew G Sprau; Eboni Smith; Maurine Tong; Kimberly F Doheny; Elizabeth W Pugh; Richard M Watanabe; Thomas A Buchanan; Timo T Valle; Richard N Bergman; Jaakko Tuomilehto; Karen L Mohlke; Francis S Collins; Michael Boehnke Journal: Diabetes Date: 2007-01 Impact factor: 9.461
Authors: Elodie M Girault; Pim W Toonen; Leslie Eggels; Ewout Foppen; Mariëtte T Ackermans; Susanne E la Fleur; Eric Fliers; Andries Kalsbeek Journal: Psychoneuroendocrinology Date: 2013-07-13 Impact factor: 4.905
Authors: Robert W Buchanan; Julie Kreyenbuhl; Deanna L Kelly; Jason M Noel; Douglas L Boggs; Bernard A Fischer; Seth Himelhoch; Beverly Fang; Eunice Peterson; Patrick R Aquino; William Keller Journal: Schizophr Bull Date: 2009-12-02 Impact factor: 9.306