摘要
目的观察重组人胰高糖素样多肽-1(7-36)对GK大鼠体重、糖代谢指标、β细胞功能及团块量的影响。方法34周龄雄性GK大鼠51只随机分为3组:GK低剂量(GK LD)、高剂量(GK HD)及生理盐水组(GK NS),Wistar大鼠15只为正常对照组(Wistar NS)。各组大鼠分别接受人胰高糖素样多肽GLP-1(LD:GLP-1 56μg/kg,HD:GLP-1 133μg/kg)或NS皮下注射共12周。实验中随访大鼠体重、血糖(空腹及餐后)及糖化血红蛋白(HbA1c)水平。实验结束前行腹腔糖耐量实验(IPGTT)评价葡萄糖刺激的胰岛素分泌能力(GSIS),之后处死大鼠取下胰腺,通过免疫组织化学及形态测量学方法计算β细胞团块量。结果GK LD、HD组在GLP-1干预后,体重略减轻、进食后血糖较NS组下降,差异有统计学意义[体重:2周:LDvsHDvsNS:(361.94±20.16)vs(363.47±24.12)vs(368.65±24.19)g,P<0.05,血糖:11周:30min:LDvsHDvsNS:(10.80±1.08)vs(12.00±2.88)vs(14.10±3.52)mmol/L,P<0.001;60分钟血糖:LDvsHDvsNS:(16.30±2.69)vs(16.00±2.51)vs(22.44±2.84)mmol/L,P<0.001],胰腺β细胞团块量增加,差异有统计学意义[LDvsHDvsNS:(13.75±3.85)vs(15.13±3.48)vs(7.87±3.55)mg/胰腺,P<0.05]。空腹血糖、HbA1c及GSIS指标较GK NS组未有明显改善。结论通过皮下注射方式给予GK大鼠rhGLP-1(7-36)12周可轻度减轻体重;降低进食后血糖;提高胰腺β细胞团块量且具有剂量依赖趋势。但空腹血糖、HbA1c及GSIS未见改善。
Purpose This study was aimed to investigate the effectiveness of recombined human glucagon-like peptide-1 （rhGLP-1） 7-36 on body weight, blood glucose metabolism, β cell function and mass of GK rat. Methods Fifty-one 34-week old GK rats were randomly assigned into three groups： GK low dose group （GK LD）, high dose group（GK HD） ,and GK NS group. Fifteen Wistar rats were used as normal controls （Wistar NS）. Each group received GLP-I（LD： 56 μg/kg, HD： 133 μg/kg） or normal saline subcutaneous injuection respectively for 12 weeks. Body weight, blood glucose （both fasting and postprandial） and serum HbAlc levels of each group were followed. All rats were subjected to an introperitoneal glucose tolerance test （IPGTT） on week 12. Pancreases were removed and fixed after IPGTT. Immunohistochemical study was carried out and quantitative evaluation of β cell mass of each group was performed using a computer-assisted image analysis procedure. Results GK LD and HD group both had slightly lower body weight and significantly lower postprandial blood glucose than GK NS group [LD vs HD vs NS weight on week 2 （361..94 ± 20.16）vs （363.47 ± 24. 12） vs （368.65 ± 24.19） g, P〈0.05; postprandial blood glucose on week 11 for 30 min： （10.80 ± 1.08） vs（12.00 ± 2.88） vs （14.10 ± 3.52） mmol/L, P〈0. 001 ; for 60 min： （16.30 ± 2.69） vs （16. 00 ± 2.51） vs （22.44 ± 2.84） mmol/L,P〈0. 001）. Pancreatic 13 cell mass of rhGLP-1 receiving group were increased （LD vs HD vs NS： （13.75 ± 3.85） vs （15.13 ± 3.48） vs （7.87 ± 3.55） mg/pancrease, P〈 0.05]. No improvements of fasting blood glucose, serum HbAlc level and GSIS were observed after GLP-1 treatment. Conclusions GK rats treated with rhGLP-1 subcutaneously injection for 12 weeks has slightly lower body weight and significantly lower non-fasting blood glucose. Pancreastic β cell mass is increased by GLP-1 treatment and might be dose dependent. No improvements of fasting blood glucose, serum HbAlc leveland GSIS were observed after rhGLP-1 treatment.
出处
《复旦学报（医学版）》
CAS
CSCD
北大核心
2007年第1期111-115,共5页
Fudan University Journal of Medical Sciences
