Effects of clozapine on rat insulin secretion cultured in vitro:no correlation between dosage and basal insulin secretion
- VernacularTitle:氯氮平对体外培养大鼠胰岛分泌功能的影响剂量基础胰岛素分泌无关
- Author:
Gaohua WANG
;
Huiling WANG
;
Yuan ZHOU
;
Xiaoping WANG
;
Shenhong WENG
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2005;9(31):231-233
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Glucose metabolism disturbance, one of clozapine's adverse effects, has received increasing attention from endocrinologists. Insulin resistance is believed to be associated with clozapine-induced glucose metabolism disturbance. Does it have direct effects on secretion function of islets?OBJECTIVE: To investigate the effects of different concentrations of clozapine on the secretion function of pancreatic islets in vitro.DESIGN: A completely randomized controlled design for the experimental study.SETTING: Department ofPsychiatry, People's Hospital of Wuhan University.MATERIALS: The experiment was conducted in the Laboratory Center of Stomatology Hospital of Wuhan University from September 2003 to January2004. Three healthy male Wistar rats of clean grade were used.METHODS: [1] Classical collagenase digestion method was used to isolate and purify the rat islets of Langerhans. [2] Hank's solution containing 2 g/L bovine serum albumin and 3.3 mmol/L glucose was added for preincubation for 30 minutes. The supernatant was removed. The wells were divided into five groups with 12 wells in each group. The control group was added with 1 g/L dimethyl sulphoxide (DMSO) and 3.3 mmol/L or 16.7 mmol/L glucose, 1 mL per well. The four experimental groups were added with 1 mL 0.2 μmol/L, 1 μmol/L, 5 μmol/L, or 10 μmol/L clozapine apart from the above DMSO and glucose. Six wells in each group were incubated for 1 hour, and another six wells were incubated for 4hours. The supernatants of the different groups were collected and stored at-20℃ in the refrigerator for later testing. The above procedures were repeated three times. The insulin released into the medium supernatant was examined by radioimmunoassay. [3] One-way ANOVA was used to compare the differences between the experimental groups and control group; LSD-t test was used for multiple comparison.MAIN OUTCOME MEASURES: The level of insulin secretion in the supernatants in culture solution containing 3.3 mmol/L or 16.7 mmol/L glucose which was incubated for 1 hour or 4 hours.RESULTS: [1] At 3.3 mmol/L glucose, no difference in insulin secretion was found between the four clozapine groups and control group after 1-hour incubation (P ＞ 0.05). After 4-hour incubation, the level of insulin in clozapine groups decreased significantly [(0.92±0.4), (1.02±0.3),(1.06±0.4), (0.74±0.2), (1.66±0.4) mU/IEQ, P ＜ 0.05]. There was no significant difference in the volume of insulin among the four clozapine groups with different concentrations (P ＞ 0.05). [2] At 16.7 mmol/L glucose, the level of insulin at the four concentrations of clozapine did not differ from that of control group either after 1 hour or 4 hours of incubation (P ＞ 0.05).CONCLUSION: Clozapine inhibits basal insulin secretion, but the effect is not correlated with its dosage.
