PMID- 24692793
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140402
LR  - 20211021
IS  - 0011-393X (Print)
IS  - 0011-393X (Linking)
VI  - 69
IP  - 2
DP  - 2008 Apr
TI  - Effects of clozapine administration on body weight, glucose tolerance, blood 
      glucose concentrations, plasma lipids, and insulin in male C57BL/6 mice: A 
      parallel controlled study.
PG  - 142-9
LID - 10.1016/j.curtheres.2008.04.007 [doi]
AB  - BACKGROUND: Clozapine has been associated with metabolic adverse events (AEs) 
      (eg, elevated body weight, blood glucose concentrations, cholesterol, 
      triglycerides [TG]), all of which have deleterious effects on health and 
      medication compliance. However, little focus has been directed toward finding a 
      suitable experimental model to study the metabolic AEs associated with clozapine. 
      OBJECTIVE: The aim of this study was to assess the effects of clozapine 
      administration for 28 days on body weight, glucose tolerance, blood glucose 
      concentrations, plasma lipids, and insulin in C57BL/6 mice. METHODS: C57BL/6 mice 
      were grouped and treated with clozapine 2 or 10 mg/kg or vehicle 
      intraperitoneally QD for 28 days. Body weight was assessed on days 0 (baseline), 
      7, 14, 21, and 28, and glucose tolerance, blood glucose concentrations, insulin 
      (calculated by insulin resistance index [IRI]), and plasma lipids (including 
      total cholesterol, TG, high-density lipoprotein cholesterol [HDL-C], and 
      low-density lipoprotein cholesterol) were assessed on day 29. RESULTS: Sixty 
      10-week-old, male C57BL/6 mice were included in the study and were divided into 3 
      groups (20 mice per group). The body weight significantly decreased in the 
      clozapine 10-mg-treated group on days 14, 21, and 28 compared with the vehicle 
      group (mean [SD] body weight: 21.61 [1.05] vs 22.79 [1.11], 22.53 [1.05] vs 24.17 
      [1.24], and 22.21 [1.07] vs 24.99 [1.39] g, respectively; all, P < 0.05). In the 
      clozapine 10-mg/kg group, blood glucose concentrations significantly increased 0, 
      30, 60, and 120 minutes after glucose administration compared with the vehicle 
      group (mean [SD]: 6.67 [1.25], 25.34 [5.85], 12.68 [3.39], and 7.52 [1.45] 
      mmol/L, respectively, vs 4.61 [0.78], 21.54 [6.55], 11.46 [3.46], and 6.55 [1.42] 
      mmol/L, respectively; all P < 0.05). The clozapine 10-mg/kg group also had 
      significant increases in plasma insulin concentrations compared with the vehicle 
      group (12.70 [5.27] vs 7.62 [4.54] muIU/mL; P < 0.05) and IRI (3.01 [1.26] vs 1.51 
      [0.96]; P < 0.05). Plasma HDL-C concentration also significantly decreased in the 
      clozapine 10-mg/kg group compared with the vehicle group (1.23 [0.25] vs 1.47 
      [0.16]; P < 0.05). CONCLUSION: Clozapine 10 mg/kg was associated with significant 
      decreases in body weight and significant increases in fasting blood glucose and 
      glucose tolerance in these male C57BL/6 mice.
FAU - Yuan, Hai-Yan
AU  - Yuan HY
AD  - Clinical Pharmacy and Pharmacology Research Institute, Second Xiangya Hospital, 
      Central South University, Changsha, China.
FAU - Liang, Hai-Xia
AU  - Liang HX
AD  - Clinical Pharmacy and Pharmacology Research Institute, Second Xiangya Hospital, 
      Central South University, Changsha, China.
FAU - Liang, Guang-Rong
AU  - Liang GR
AD  - Department of Pharmacy, Nanhua Hospital, Nanhua University, Hengyang, China.
FAU - Zhang, Gui-Xiang
AU  - Zhang GX
AD  - School of Pharmaceutical Sciences, Central South University, Changsha, China.
FAU - Li, Huan-De
AU  - Li HD
AD  - Clinical Pharmacy and Pharmacology Research Institute, Second Xiangya Hospital, 
      Central South University, Changsha, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Curr Ther Res Clin Exp
JT  - Current therapeutic research, clinical and experimental
JID - 0372621
PMC - PMC3969929
OTO - NOTNLM
OT  - blood glucose
OT  - body weight
OT  - clozapine
OT  - insulin resistance
OT  - mice
OT  - plasma lipid
EDAT- 2008/04/01 00:00
MHDA- 2008/04/01 00:01
PMCR- 2008/04/01
CRDT- 2014/04/03 06:00
PHST- 2007/11/28 00:00 [accepted]
PHST- 2014/04/03 06:00 [entrez]
PHST- 2008/04/01 00:00 [pubmed]
PHST- 2008/04/01 00:01 [medline]
PHST- 2008/04/01 00:00 [pmc-release]
AID - S0011-393X(08)00041-6 [pii]
AID - 10.1016/j.curtheres.2008.04.007 [doi]
PST - ppublish
SO  - Curr Ther Res Clin Exp. 2008 Apr;69(2):142-9. doi: 
      10.1016/j.curtheres.2008.04.007.