High-fat diet aggravates islet beta-cell toxicity in mice treated with clozapine.
BACKGROUND
Clozapine, an atypical antipsychotic drug, induces derangements in glucose homeostasis in certain patients. This study investigated the mechanisms of clozapine-induced beta-cell toxicity.


METHODS
Fifty-two healthy C57BL/6 male mice were randomized into 4 groups to study the effects of clozapine (group C, D) and a high-fat diet (group B, D). Three mice from each group were randomly selected to determine the amount of food intake on days 8-10, and their pancreases were removed for histological examination on day 11. The remaining 10 mice in each group were sacrificed at the 8th week to measure pancreatic insulin content (PIC).


RESULTS
Mice given clozapine for 8 weeks demonstrated trends of lower PIC. The histological examination of the pancreases retrieved on day 11 already revealed apoptotic changes and suppression of cell proliferation. Although mice fed high-fat chow gained weight, mice given both clozapine and a high-fat diet showed less weight gain and more severe histological deterioration, and had the lowest PIC levels of the 4 groups.


CONCLUSIONS
Pancreatic beta-cell apoptosis, suppression of cell proliferation, and trends of reduction in pancreatic insulin content were observed in mice taking clozapine. The findings of clozapine induced beta-cell toxicity were further aggravated when mice were concomitantly fed a high-fat diet.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Chung-Huei
CH
Huang
Shin-Huei
SH
Fu
Samuel
S
Hsu
Yu-Yao
YY
Huang
Szu-Tah
ST
Chen
Brend Ray-Sea
BR
Hsu
D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D003024:Clozapine / Q000633:toxicity*; D059305:Diet, High-Fat; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D014150:Antipsychotic Agents; D003024:Clozapine