P-185

High-fat diet aggravates islet beta-cell toxicity in mice fed with clozapine

B. Hsu, S.H. Fu, S. Hsu, S.T. Chen, Y.Y. Huang
Chang-Gung Memorial Hospital and University, Division of Endocrinology and Metabolism, Tao-Yuan Hsien, Taiwan

Objective: Clozapine, an atypical antipsychotic drug, induces derangements in glucose homeostasis via beta-cell toxicity and increases insulin resistance. Feeding of high-fat diet results in a compensatory increase of islet beta-cell mass in healthy mice. It is interesting to study the effect of high-fat diet feeding on the clozapine-induced beta-cell toxicity.

Methods: We randomly separated 52 healthy B6 male mice into A, B, C and D groups. Mice in groups A and B were fed with regular diet while mice in groups C and D were fed with high-fat diet. Mice in groups B and D were orally administrated with 15 mg/kg body weight of clozapine daily. Blood glucose and body weights were measured three times a week. The amount of food intake was determined at days 8, 9 and 10 and the pancreas from three mice in each group was removed for histological examination at day 11. The pancreatic insulin content (PIC) from remaining mice was determined at 8-weeks of observation.

Results: The daily intake calories among four groups did not differ. The body weight increments and PIC in group B were significantly higher than those of mice in group D (8.69±1.16 vs. 1.39±1.23 g and 4.56±0.46 vs. 1.67±0.21 ?g). The body weight increments were 2.80±0.30 and 1.04±0.33 g, and the PIC was 3.25±0.31 and 2.37±0.21 ?g in groups A and C, respectively. The histological examination of pancreas retrieved at day 11 revealed that islets of mice receiving both high-fat diet and clozapine had the highest apoptosis ratio. The quantity of advanced glycation end products (AGEs) in serum was 122±17, 99±7, 90±4 and 195±75 ng/mL at day 11 and 168±11, 175±16, 145±11 and 3859±1638 ng/mL at day 56 in groups A, B, C and D, respectively.

Conclusions: Feeding of high-fat diet aggravates clozapine-induced toxicity on islet beta-cells in healthy mice.

P-185

High-fat diet aggravates islet beta-cell toxicity in mice fed with clozapine

B. Hsu, S.H. Fu, S. Hsu, S.T. Chen, Y.Y. Huang
Chang-Gung Memorial Hospital and University, Division of Endocrinology and Metabolism, Tao-Yuan Hsien, Taiwan

Objective: Clozapine, an atypical antipsychotic drug, induces derangements in glucose homeostasis via beta-cell toxicity and increases insulin resistance. Feeding of high-fat diet results in a compensatory increase of islet beta-cell mass in healthy mice. It is interesting to study the effect of high-fat diet feeding on the clozapine-induced beta-cell toxicity.

Methods: We randomly separated 52 healthy B6 male mice into A, B, C and D groups. Mice in groups A and B were fed with regular diet while mice in groups C and D were fed with high-fat diet. Mice in groups B and D were orally administrated with 15 mg/kg body weight of clozapine daily. Blood glucose and body weights were measured three times a week. The amount of food intake was determined at days 8, 9 and 10 and the pancreas from three mice in each group was removed for histological examination at day 11. The pancreatic insulin content (PIC) from remaining mice was determined at 8-weeks of observation.

Results: The daily intake calories among four groups did not differ. The body weight increments and PIC in group B were significantly higher than those of mice in group D (8.69±1.16 vs. 1.39±1.23 g and 4.56±0.46 vs. 1.67±0.21 ?g). The body weight increments were 2.80±0.30 and 1.04±0.33 g, and the PIC was 3.25±0.31 and 2.37±0.21 ?g in groups A and C, respectively. The histological examination of pancreas retrieved at day 11 revealed that islets of mice receiving both high-fat diet and clozapine had the highest apoptosis ratio. The quantity of advanced glycation end products (AGEs) in serum was 122±17, 99±7, 90±4 and 195±75 ng/mL at day 11 and 168±11, 175±16, 145±11 and 3859±1638 ng/mL at day 56 in groups A, B, C and D, respectively.

Conclusions: Feeding of high-fat diet aggravates clozapine-induced toxicity on islet beta-cells in healthy mice.